Praveen Kumar Gaur1lowast Shikha Mishra2 Rohit Gautam1 Alok Pratap Singh1 and Mohd Yasir11Department of Pharmaceutics ITS Paramedical College (Pharmacy) Muradnagar Ghaziabad UP 201206 India2Department of Pharmacognosy and Phytochemistry Jamia Hamdard New Delhi 110062 India
Film coating has evolved with time keeping in pace with the demands of the Pharmaceutical industry There has beentremendous and necessary modification like improved production equipment and the development of highly efficient film-coating formulations and polymers which has accelerated the acceptance of film-coating technology Film coating hastaken over sugar coating owing to the broader flexibility and additional functionalities in former There has been stateof the art level improvisation in methodology and technique exemplified by solvent or water based and dry coating Themain focus of this literature review is to summon up the different types of coating technologies and various parametersand variables that play a major role during the entire process Commentary on future direction is also provided
KEYWORDS Film Coating Aqueous Coating Dry Coating Process Parameters
INTRODUCTIONEach drug has its own characteristics like bitternessunpleasant odour lightsensitivity or hygroscopicity Tabletcoating was done to solve such problems in conventionaldosage form Previously sugar coating was mostly appliedto achieve this purpose But it was skilled manipulative andtime consuming process that could last for even five days soit got replaced by film coating (Porter 2011) The operatorhad to be highly skilled for such coating Hence film coat-ing was preferred and eventually it replaced sugar coatingThe current drugs are diverse in chemical nature as well
as in physical attributes It can give a bitter taste in themouth or has an unpleasant odour Such properties can beappropriated by using coating technology which can in turnimprove the patient compliance (Fig 1) Further the coremay contain a substance which is light sensitive or affectedby oxidation so coating can be added to improve stabil-ity by acting as a physical barrier to environmental storageconditions The coating develops the mechanical integritywhich means coated products are more resistant to mishan-dling (abrasion attrition etc) It also improves the appear-ance and creates a unique look for identification The majorattribute of coating is modulation of release profile egextended release enteric coating (delayed release) osmotic
lowastAuthor to whom correspondence should be addressedEmail gaurmpharmarediffmailcomReceived 15 September 2013Accepted 25 October 2013
pump pulsatile delivery thereby improving upon bioavail-ability and therapeutic potential of a drug On a differentnote coating reduces friction and increases packaging rate(Lachman et al 1989 Libermen and Lachman 2003)
BASIC PRINCIPLE INVOLVED INTABLET COATINGCoating may be applied to a wide range of oral soliddosage forms including tablets capsules multi partic-ulates and drug crystals by applying spray-atomisationtechnique Primary components involved in tablet coatingare properties of tablet processing variables equipmentsancillary equipments and automation in coating processeseg coating process design and control Usually the coat-ing mixture is sprayed through a nozzle onto the tablets asthe tablets are being agitated in a pan or fluid bed A filmof coating liquid is formed on tablet surface as the coatingmixture is sprayed This film can be formed with a singleapplication or through multiple spraying in a batch pro-cess consisting batch identification and formula selectionloading heating spraying cooling and drying (Libermenand Lachman 2003)
CLASSIFICATIONOrganic Solvent BasedIn the early 1950s film coating was performed by applyingthe polymers dissolved in organic solvents which providedseveral benefits over sugar coating such as less processing
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Film Coating Technology Past Present and Future Gaur et al
Figure 1 Chronological development (Decade wise) in coating technology
time possibility of preparing thin smooth continuous coat-ings and reduced risk of hydrolysis (Fig 2)The film formation occurs due to removal of the sol-
vent causing an increase in concentration of polymerresembling a gel However coating with organic solutionsdecreased in popularity due to the restrictions concerninghazardous solvents On the other hand environmental con-cerns and regulatory issues enhanced the production costsdue to solvent recovery (Savage and Rhodes 1995)
Aqueous Based CoatingSolutionsPrimary requirement for the polymer is to be water solu-ble These systems have been used as protective coatingsas they result in water-soluble films without any releasemodifying effects Commonly used hydrophilic polymersare cellulose derivatives such as HPMC however PVPPVA and PEGs are also suitable Small molecular weightpolymers are favoured to optimize the ratio of solid con-tent to viscosity for the coating formulation Optimal inter-action of the polymer can be obtained by the use ofwater-soluble plasticisers eg glycerol propylene glycolor triacetin (Lehmann 1994 Porter 1990)
DispersionsRecently aqueous polymer dispersions are being usedin coating of water-insoluble polymers due to increas-ing concerns about the toxicity of the organic solventsenvironmental pollution and cost-intensive solvent recov-ery systems The size of the polymer particles in thesetwo-phase systems is in the colloidal range with the upperlimit around 1 m to ensure good storage stability Themain property of these dispersions is their low viscositydespite their high solids content which may reach up to30 of the total formulation (Dillon et al 1951)The major problem related to aqueous coating systems
is prolonged processing time due to the higher heat ofvaporization of water however this problem was eradi-cated by modified equipment design such as developmentof side-vented perforated coating pans and fluidized bedequipment for increased drying efficiency Process automa-tion and the concept of validation have resulted in a strongincrease of productivity The film formation from aque-ous colloidal dispersions is a complex multi-step processThe polymer particles are closely packed upon increasingconcentration of the dispersion due to water evaporationIn this ordered arrangement the polymer particles comeinto contact with each other for the first time Further
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Gaur et al Film Coating Technology Past Present and Future
Figure 2 Types of film coating
water loss goes along with a deformation of the particlesforming a denser array (Cole 1998) Dry sintering andcapillary forces are considered as possible mechanisms forthe particle deformation Finally in the last stage of film
formation the individual particles lose their identity afterthe diffusion of polymer chains through the boundary andformation of a continuous film with adequate mechanicalproperties occurs The performance of the resulting film ishighly affected by the temperature during film formationIf the temperature remains above the boiling temperatureof water the vapour pressure during film-formation maybe sufficient to burst the surface film layer causing voidsand pinholes These imperfections may be responsible forhigher water vapour permeability or enhanced drug release(Harris and Sellassie 1997)
Redispersible PowdersThese systems were originally developed for enteric poly-mers which were esters prone to hydrolysis in aque-ous media (Porter 1990) eg Aquateric the commercialredispersible powder of cellulose acetate phthalate (CAP)or redispersible Eudragit L enteric variant of methacrylicacid copolymer (Bodmeier and Paeratakul 1994) Addi-tional advantages of redispersible powder formulations areless propensity for flocculation when exposed to high shearforces or temperature changes reduced storage and ship-ping cost and enhanced microbiological stability Redis-persible polymer powders are usually prepared throughfreeze- or spray drying of polymer dispersions But it isimportant that the properties of the original polymer dis-persions are regained after the redispersion of the polymerpowder especially the original particle size distributionsince an increase in the particle size can affect the filmformation negativelyThe film formation from aqueous dispersion occurs by
coalescence of particles in a continuous film (Fig 3) Thecoalescence of aqueous polymer dispersion is initiated bywater evaporation which pushes dispersed polymer parti-cles into a closely packed ordered array with water filledvoids After the polymer particles come into contact witheach other they deform and fuse in order to coalesce intoa film Coalescence occurs when the promoting forces aregreater than the resistive forces of the particles Film forma-tion ie coalescence is a complex process and depends oncoating and storage conditions coating polymer polymer
Water vaporization
Water vaporization
Aqueous dispersion of coating material depositedon the surface of the tablet
Compaction and deformation of coating materialon the surface of the tablet
Coalescence of coating material on the surface ofthe tabletand form a film
Figure 3 Mechanism of aqueous polymer film formationprocess
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Film Coating Technology Past Present and Future Gaur et al
molecular weight and particle size coating liquid con-stituents and properties like viscosity and surface Sincecoalescence occurs above a minimum film formation tem-perature (MFT) temperature and rate of water evaporationare major process-related factors affecting the properties ofcoatings Usually a thermal after-treatment (curing) is doneto remove the film defects (Aulton 1995 Lachman et al1989)
Process ParametersThe spraying rate affects the moisture content which inturn affects quality and uniformity of the film A low sprayrate will give a brittle film due to incomplete coalescencedue to inadequate wetting and a high spray rate causesover wetting resulting in picking and sticking The sprayrate also interacts with tablet temperature and a low tablettemperature with high spray rate can produce cracks inthe film Increase in pressure reduces the surface rough-ness by producing thin dense film however excessive pres-sure forms very fine droplets which spray dries beforegetting to tablet bed causing spray loss The inlet air tem-perature impacts the drying process and coating unifor-mity High temperature enhances the drying efficiency anddecreases the water penetration however too much air tem-perature can cause premature drying and reduces the effi-ciency Since water is less volatile than organic solventsand requires higher drying capacity resulting in higherenergy cost of the entire coating process Ideal Cures PvtLtd has developed some products (INSTACOAT rangefor example Instacoat EHP 250 Instacoat EMB InstacoatEEN Instacoat EHA Instacoat Aqua Instacoat Aqua IIInstacoat Aqua III and Instacoat P4) which dries faster andthe whole coating process can be completed in the sameor sometimes little less time as compared to organic sol-vent based coatings The increase in rotating speed canimprove the mixing but to a certain level An increase inthe pan speed reduces variation in thickness and enhancesthe coating uniformity however a excessively high speedcan lead to undesired breakage
Air Pressure of AtomisationUsually the drug should be stable to withstand all the pro-cessing parameters as per the specification however it isimportant to consider the properties of the drug There is astrong potential of interaction that can occur between thedrug and polymeric material or any other additive Poly-meric material after atomisation can possibly dissolve theouter layer of the substrate and the components of the lat-ter may also migrate eg migration and subsequent recrys-tallization of propranolol HCl in Eudragit NE 30D filmsso sub-coating is done to overcome this problem as it pre-vents interactions and it is suitable when enteric coatingis being done on an acid-labile drug as enteric coatingpolymers are acidic in nature (Rekhi et al 1995)Size and shape of the substrate is also of consider-
able importance as its movement within the equipment is
deeply influenced A biconvex round tablet is preferred asflat tablets tend to agglomerate during the process Thereare possibilities of shallow convex tablets undergoing abra-sion due to its sharp edges and thus sub-coating becomesessentialSurface wettability is important as wetting and spread-
ing of the polymer material is related to the smoothness ofthe film and adhesion to the substrate Coated multipartic-ulate systems offer several advantages over larger singleunit dosage forms especially when applied to modified-release coatings due to greater uniformity in GI transittime and a reduced potential for premature release Thesecoated particles can be filled into capsules or compressedinto tablets When compressing coated particles the forceused during the tabletting process and the mechanicalstrength of the coating are critical Faster drug release mayoccur if the film cracks or fractures during compactionwhile slower drug release has been reported when the coat-ings fuse together to form a matrix Excipients such asmicrocrystalline cellulose minimize direct contact of thecoated pellets and dissipate the compression forces to pre-vent film fracturePolymeric films adhere to the substrate surface using
two major forces namely the strength of the interfa-cial bonds and the internal stresses within the film Theprimary type of interfacial bonding is hydrogen bond for-mation although dipole and dipole-induced dipole interac-tions also occur Substrate considerations such as surfaceroughness tablet hardness and substrate hydrophobicitycan affect the strength of interfacial bonding In contrastinternal stresses which arise from forces due to shrinkageof the film upon solvent evaporation thermal stress due tothe differences in thermal expansion of the film and thesubstrate and volumetric stress due to swelling during stor-age tend to weaken adhesion Use of excipients with ther-mal expansion coefficients similar to that of the polymercan reduce internal stresses and improve polymer adhesion(Lippold and Monells 2001 Okutgen et al 1991 Franzand Doonan 1983)
Dry CoatingThere are several disadvantages of using the solventswhether aqueous or organic eg drying time and microbi-ological stability for aqueous coating whereas safety andenvironment hazards for organic solvents These issueshave led to the adoption of dry powder coating techniquesin a number of other industries Among these are technolo-gies which range from the atomization of molten materialscommonly known as melt coating to softened powder lay-ering and electrostatic adhesion Types of Dry Coating areas follows (Felton and Porter 2013)
Electrostatic Dry CoatingThis novel coating technique is an alternative to aqueousor solvent based coating process is widely useful in foodtechnology paint technology metal coatings coating of
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Gaur et al Film Coating Technology Past Present and Future
living cells and coating of tablets as well as capsules Theprinciple of electrostatic powder coating states that spray-ing of a mixture of finely grounded particles and polymersonto a substrate surface without using any solvent and thenheating the substrate for curing in oven until the powdermixture is fused into filmAccording to the charging mechanism there are two
types of spraying units namely(a) Corona charging(b) Tribo charging
Magnetically Assisted Impaction CoatingIn this technique the particles are assumed to stay in afluidized state where the distribution of velocities is aMaxwellndashBoltzmann type It is assumed that the collisionsoccurring among the particles are important for impingingthe guest particles onto the surface of host particles therebymaking a transient surface on the host particles The coatingtime depends on various parameters eg properties of thehost and guest particles number of host particles height ofthe fluidized bed and ratio of the host and guest particlesdiameters For a particular coating time the bed height andparticle size should be optimum (Singh et al 2001)
Film Formation Mechanisms inDry Powder CoatingFilm formation takes place by a process of evaporationcoalescence and sintering which are influenced by pro-cess and formulation considerations During the dry pow-der coating process the substrates are often heated abovethe glass transition temperature of the layering materialsso that the coating materials soften and adhere to the sub-strate For conventional film coating spreading and adher-ence is not limited by mobility however powder systemsmay become limited by mobility particularly when liquidlevels are reduced to the point where solid particle defor-mation becomes rate limiting This introduces a series ofconstraints related to mechanical and thermal propertiesof the coating formulation Coalescence and film forma-tion are therefore dependent on these properties as wellAs such glass transition temperature and plastic deforma-tion characteristics of the coating materials are paramountto the success of the process Many pharmaceutical coat-ing materials are amorphous polymers exhibiting a glasstransition temperature related to the change from a glassto a super cooled liquid On transition which occurs at aspecific temperature mobility of the system increases sig-nificantly The greater mobility allows for molecular rear-rangement and alters the plastic deformation characteristicsof the materialsThe mechanism of film formation of the powders lay-
ered onto the solid cores ismdashsummarized as (Felton andPorter 2013 Felton 2007)(i) Coalescence and sintering of the particles of the poly-meric materials in a process that involves the partial fusionof the polymer
(ii) Levelling of the coating material includes densifica-tion of the layer with reduction of the empty spaces andsmoothening of the surface(iii) Cooling of the layer and hardening of the coating
Based on FunctionProtective CoatingsThin films of water soluble polymers are often appliedfor taste or odour masking or to improve the stabilityof moisture sensitive products or for better mechanicalresistance of the product during handling Such protectivecoatings need to remain intact for the short time of swal-lowing and after that they should immediately dissolve toensure immediate drug release These polymers are water-soluble eg cellulose ethers (eg hydroxypropyl methyl-cellulose (HPMC)) polyvinyl acetate (PVA) or polyvinylpyrrolidone (PVP) Eudragitreg E is a methacrylic copoly-mer insoluble in saliva but rapidly dissolves in the acidicpH of the stomach Sometimes enteric polymers eg shel-lac can also be applied at very low concentration whichgives very low film thickness insufficient to provide gastricresistance and disintegrates in the stomach within 30 min(Lehmann 1994 Porter 1990 Porter 2011)
Functional CoatingsFilm coatings which are applied to achieve a desiredrelease profile are usually termed modified-release orfunctional coatings Those intended to protect the drugfrom the acidic environment of the stomach are entericcoatings Extended release coatings in contrast areintended to control the release of the drug over a prolongedperiod of time (Porter 1990)Enteric Coatings Enteric coatings are prepared from
gastric resistant polymers which remain intact in stom-ach but immediately dissolve in small intestine Themost effective enteric polymers contain many carboxylicgroups with a pKa of 3ndash5 Therefore they will dissoci-ate and dissolve only when the pH rises above this value(Porter 2011 Lehmann 1994) Before the synthetic poly-mers were introduced to the market shellac a naturalpolymer was one of the main polymer used for this pur-pose Cellulose acetate phthalate (CAP) was the first syn-thetic polymer described in 1937 which soon gained highpopularity as a gastric resistant polymer Later polyvinylacetate phthalate (PVAP) and hydroxypropyl methylcel-lulose phthalate (HPMCP) were preferred due to theirlower permeability in the gastric fluid and improved sta-bility against hydrolysis Today methacrylate copolymersEudragitreg L and S are two of the most widely used poly-mers for this purpose (Malm and Waring 1937 Zheng andMcGinity 2003)Extended Release Coatings The patient compliance is
usually inversely proportional with the frequency of drugadministration especially when multiple daily administra-tions are necessary to maintain constant blood levels of the
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Film Coating Technology Past Present and Future Gaur et al
drug Therefore extended release polymers were devel-oped which are able to provide a sustained action by acontrolled release over time Waxes and some natural poly-mers were already discovered earlier to be useful to pro-long the drug release if coated onto the solid dosage formsMostly their mechanism of performance is based on slowdegradation or erosion Polymers for extended release arein general insoluble in water over the entire pH range Thedrug release is thus controlled by diffusion through thehydrated polymer or through cracks or water-filled poresThere are still only few polymers available on the mar-ket for extended release eg cellulose acetate ethylcel-lulose or the methacrylic acid copolymers Eudragitreg RSRL and NE Combinations of ethylcellulose with waxeswater-soluble or enteric polymers were investigated toachieve extended drug release for drug with varying oreven pH-dependent solubilities Synthetic polymers how-ever do not fit into the overall product concept of phyto-pharmaceutical products or as for nutraceuticals they arenot approved Therefore several attempts were undertakento achieve sustained drug release by using only naturalpolymers The drug release from silk fibroin coated tabletsafter cross-linking with a carbodiimide was extended toseveral hours (Savage and Rhodes 1995) Shellac is alsoable to provide prolonged drug release at higher coatinglevels or as matrix forming material However there is nodrug release for such systems in the gastric medium due tothe enteric property of shellac Zein as a water-insolublenatural polymer is an alternative for extended drug releaseespecially in combination with an additional enteric top-coat (Mazer et al 1992)
Active CoatingIn it the drug is embedded into the coat to formulate afixed dose combination or to modify the release profileThe beadlets are then filled into capsules however the vol-ume limitation of capsules makes it an unsuitable approachfor higher dose drugs (Seitz et al 1988)This is particularly useful for the drugs unstable at
high mechanical stress In an active coating process com-mon pharmaceutical operations can be avoided Drugs thatundergo acid or base catalysed degradation have been sta-bilized by this technique It gives relatively high drug toexcipient ratio than encapsulating such molecules in thetablet core Fixed dose combinations can be formulated bythis approach (Hogan 1998)The primary concerns of an active coating process
are end-point content uniformity efficiency and stabilitywhich are either directly or indirectly affected by pro-cess parameters such as rate of spraying inlet air temper-ature residual moisture pan speed atomisation pressureand drug properties The end point is estimated by the gainin tablet weight or quantity of coating suspension sprayedPeriodically tablets are sampled and analysed for the drugamount (Lipper et al September 11ndash12 2006) Severalmathematical models have been proposed to ascertain a
correlation between coating parameters and content unifor-mity but the model proposed by Cheng et al has confirmedto be most robust (Chen et al 2010 Chen et al 2008)Coating time is also an important parameter since a
longer coating time results in better content uniformity butit makes the process not amenable for a high volume prod-uct On the other hand too short coating time can lead toincomplete coating process Spray zone width should notbe too narrow or too wide If the tablet bed has not beenappropriately covered then there will be either unsprayedsubstrate or unused deposit of coating solutionCoating process should yield the tablets having required
polymorphic forms and the coating suspension shouldcrystallise after drying The stability is adversely affectedif the coating stays in amorphous state The polymor-phism also depends on coating excipients eg plasticisers(Narang et al 2011 Narang et al 2012 Chen et al 2010Chen et al 2008)Effectiveness of the Active Coating Process The coat-
ing efficiency improves significantly when the droplet sizeis smaller than 10 m By appropriate selection of atomiz-ing and pattern air volume the fraction of droplets smallerthan 10 microns can be reduced to improve the overallefficiency of the coating process Factors governing themsuch as high ratios of the suspension spray rate to atom-ization air flow rate suspension spray rate to pattern airflow rate or atomization air flow rate to pattern air flowrate can improve the coating efficiency
FILM COATING FORMULATIONCOMPONENTSPolymersA polymer is a large molecules made up of many identicalsubunits of monomers (Table I)
Immediate Release Coating PolymersCellulose Derivates The most widely used cellulosic
polymers is Hydroxypropyl Methyl Cellulose (HPMC)which is readily soluble in aqueous medium and forms flex-ible strong films which adhere to the core Other examplesMC (Methyl Cellulose) and HPC (Hydroxypropyl Cellu-lose) (Hogan 1998 Lachman et al 1989 Lehmann 1994)Vinyl Derivates The most widely used vinyl polymer
is Poly Vinyl Pyrrolidone (PVP) however it has inherenttackiness For better film coating its copolymer with vinylacetate is used
Modified Release Coating PolymersExtended Release Coating Polymers They are dis-
solved in organic solvent or dispersed in aqueous mediumeg highly substituted cellulose making them water-insoluble example Ethyl Cellulose (EC)Enteric Coating Polymers
(a) Methacrylic Acid The presence of carboxylic acidgroups renders this class to be insoluble in water at low pH
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Gaur et al Film Coating Technology Past Present and Future
Table I Film coatings are available based on the following polymeric materials
pH Independent polymer for rapidly disintegrating film coating
1 Neutral co-polymer Film coat E30D For film coating of tabletspellets granules powders
Natural polymer
1 Xanthan gum Film coating of tablets2 Pectin Film coating of tablets3 Chitosan Film coating of tablets4 Okra gum Film coating of tablets5 Grewia gum Film coating of tablets
(stomach) but as the pH rises towards neutrality in upperpart of the small intestine the coating gradually dissolvesExample Eudragit(b) Phthalate esters These polymers contain free car-boxylic acid making them acid insoluble however in intes-tine they become deprotonated and dissolves in basicmedia They are also called enteric coating polymers egCellulose acetate phthalate (CAP) Enteric coating poly-mers can be classified into 3 groups based on chemicalcompositions as listed below
The solubility of the polymers depend on the numberof carboxylic acid groups Enteric formulations shouldhave less than 10 drug release in 2 hours during acidstage The completion of the drug release in the continu-ation testing in the buffer stage should take place within45 min Classification of Polymers Based on Derivatives(Lehmann 1994 Libermen and Lachman 2003 Malm
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Film Coating Technology Past Present and Future Gaur et al
and Waring 1937 Sadeghi et al 2001 Ogaji and Nnoli2010 Ogaji and Hoag 2011 Ogaji et al 2013)
PlasticizersPlasticizers are relatively low molecular weight materialswhich are used as additives in pharmaceutical coating for-mulations to reduce the brittleness and increase the flex-ibility of the resulting film They act by weakening intermolecular attraction between polymer chains and facili-tating coalescence of discrete polymer spheres of aque-ous dispersed systems during film formation Adhesive andmechanical properties of the coating and subsequent drugrelease are dependent on the concentration of plasticizersto a great extent Plasticizers are non volatile componentsand therefore are responsible for the weight gain of dosageforms during coating A plasticizer has to be miscible andfulfil all the compatibility parameters with the polymerbeing usedAn important consideration is the content of plasticizer
as it can affect the glass transition temperature (Tg) soit should be experimentally determined by evaluating thechanges in Tg of polymer as the plasticizer content isincreased Tg is the temperature for amorphous polymersat which the behaviour of the film changes from hard andbrittle to soft and elastic An effective plasticizing agentis one which exhibits a greater decrease in the Tg of thefilm Changes in the mechanical properties of the poly-meric film are an indication of plasticizer efficacy (Seitzet al 1988 Wu and McGinity 2001)Plasticizers are classified into three groups
Anti-AdherentsAnti-adherents are used as additives to avoid agglomera-tion of the substrates during both the coating process andon subsequent storage One of the most common anti-adherents used in pharmaceutical coatings is talc but sinceit has to be used at high concentration it creates pro-cessing challenges including clogging of the spray noz-zle during coating and particle sedimentation It tends todecrease water vapour permeability and also the dissolu-tion rate of drugs due to its hydrophobic nature It alsoaffects the mechanical and adhesive properties of polymerfilms so now Glyceryl monostearate has been found as analternative to talc
Opacifying AgentsColorantsPigments deliver elegance and stability enhancement tothe solid dosage form Water-insoluble lakes and the iron
oxides are most commonly used pigments Colour migra-tion and stability issues have diminished the use of thewater-soluble dyes in film coating Pigments can signifi-cantly affect the mechanical and permeability properties ofthe film An inverse relation-ship between film-tablet adhe-sion and the particle size of the pigment has been reportedStudies have shown that the shape of the pigment par-ticle and the extent of polymer-particle interaction influ-ence the elastic modulus of polymeric films and surfacepolarity of pigments influences drug release In additionchemical incompatibilities between the pigment and thepolymer have also been reported predominantly relatedto the size and surface charge of the components andthe pH of the medium One important concept relevantto pigments is the critical pigment volume concentration(CPVC) this is the maximum concentration (based on vol-ume) of the insoluble material that can be incorporated intoa film without compromising film properties If the CPVCis exceeded insufficient polymer is present to surroundall the insoluble particles resulting in marked changes indifferent properties of the film Colorants are mainly clas-sified in to three types(i) Organic dyes and their lakes eg Erythrosine tar-trazine Sunset yellow(ii) Inorganic colours eg Iron oxide yellow red andblack titanium dioxide talc(iii) Natural colours eg Riboflavin Anthocyanins andCarmine
SolventsVehiclesThe key function of a solvent system is to dissolve ordisperse the polymers and other additivesThe major classes of solvents being used are aqueous
(Water) and Nonaqueous (Alcohols Ketones Esters Chlo-rinated hydrocarbons) Because of environmental and eco-nomic concerns water is the most commonly used solvent
Miscellaneous Coating Solution ComponentsSolid dosage form may be incorporated with several spe-cial materials such asFlavours and sweeteners are added to mask unpleasant
odours or to develop the taste eg fruit spirits (organicsolvent) aspartame water soluble pineapple flavourSurfactants are ancillary to stabilize immiscible or insol-
uble ingredients in the coating They facilitate substratewettability and promote coalescence of polymeric materialover the substratersquos surface eg Spans Tweens etcAntioxidants are incorporated to stabilize a dye system
to oxidation and colour change eg oximes phenols etcAntimicrobials are added to inhibit microbial growth
in the coating composition Various cellulosic materialsare mainly prone to microbial growth and they can notbe stored in solution form eg Carbamates alkylisothia-zloinone benzothiazoles etc
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Gaur et al Film Coating Technology Past Present and Future
CURRENT TRENDS IN FILM COATING ANDFUTURE DIRECTIONSOpadry formulations provided numerous advantages ver-sus the use of individual raw materials including thereduction of the number of raw materials for Qualitycontrol testing reduced preparation time reliable colour-matched formulations tremendous appearance and excel-lent mechanical parameters However opadry dispersionsolids must be stored as 10ndash15 ww aqueous solution toattain workable 300ndash600 centipoises viscosityOpadry II category consisting HPMC and polysaccha-
rides was introduced to increase productivity The mostsignificant recent advances in the development of fully for-mulated aqueous film coatings have been the introductionof new film coatings based on polyvinyl alcohol (PVA)and sodium carboxymethylcellulose (NaCMC) PVA-basedfilms are known to have relatively low permeability formoisture vapour and oxygen whereas NaCMC-based coat-ings are glossy and have low oxygen permeability andrelatively high permeability for water vapourOpadry aqueous moisture barrier (AMB) and Opadry II
85 series are two proprietary families of PVA-based prod-ucts that were commercialized in the mid to-late 1990sThe Opadry AMB formulation were optimized to providethe lowest moisture vapour transmission rate Opadry II85 products give moisture vapour transmission rate almostas low as Opadry AMB but can be applied at significantlyhigher spray ratesFilm coatings based on PVA and NaCMC offer various
advantages Now moisture-sensitive drugs can be coatedin an aqueous coating process by PVA-based coatingsNaCMC based coatings provide demonstrable oxygenbarrier properties and excellent aesthetic characteristics(Porter and Felton 2010)
Supercelltrade Coating TechnologyThe ldquostandardrdquo practice of tablet coating often delivers anon-homogenous product Because the tablets are loadedin large rotating pans and vented for hot air drying edgesof tablets can get grounded off and intagliation can getfilled in by coating material leading to uneven coating onedgescorners and tablet faces This inaccuracy limits theuse of modified release coatings In a laboratory it is nec-essary to coat several kilograms of tablets at one timemaking RampD of a tablet dosage form costly and difficultFurther extremely hygroscopic as well as flat or other
oddly shaped tablets cannot be coated using present tech-nology so SCT (Niro Pharma Systems) technology uses asmall modular design that accurately deposits controlledamounts of coating materials on friable and extremelyhygroscopic tablets SCTrsquos continuous small-batch capablecoating process is predictable and efficient In SCT thetablets are coated in batches ranging from 30 to 120 gramswhich linearly scale up to production capacity In this tech-nique the tablets are covered with the polymer spray in
the same direction as the hot air resulting in an efficientprocess Due to SCTrsquos unique air distribution plate designthe tablets move very quickly and predictably through thespray zone receiving only a small amount of coating perpass and therefore achieving higher coating accuracy Theprocess time is short in seconds or in minutes as opposedto hours and therefore gentler on the tablets (Systems2012)Supercelltrade Coating Technology may also be used for
coating of flat or highly oblong tablets or friable tabletsIn this process drying is very fast making it possible tocoat extremely hygroscopic tablets The deposition accu-racy is sufficiently high to layer API onto tablets and uni-form layers of taste masking or modified release coatingscan be applied consecutively within a single continuousbatchUnique features of super cell coating technology are
(1) Continuous coating(2) Short processing time(3) Flexible modular design(4) No scale-up to parameters(5) Batch size for RampD (Minimum size sim30 grams)(6) Enhancing technology(7) Multi-layer coating(8) Low humidity process suitable for moisture sensitivematerials
Syloidreg FP Silicas inPharmaceutical Film CoatingsRecently film coatings have also shown encouragingresults to enable the oral delivery of peptide therapeuticsSyloidreg FP silicas have been used as excipients in manypharmaceutical formulations due to their unique morphol-ogy The combined adsorption capacity porosity particlesize and greater surface area allow them to provide severalbenefits simultaneously which can expedite manufacturingand improve efficacy of the final dosage form Syloidreg FPsilica can be used in polymeric coating systems in combi-nation of vinylcellulose or acrylic polymers (13 Septem-ber 2010)In standard concentrationsmdashAddition of Syloidreg 244FP
silica to film coating provides following advantages-Improved spray propertiesElimination of the need for talcImprovement of suspension propertiesPrevention of valve cloggingMinimal settling in spray linesSmoothen tablet surfaceReduction of adhesionApplications Anti-tacking agent Oral peptide deliveryODT formulations Enteric coatings Sustained releasecoatings Controlled release coatings (Grace Discovery)In recent years there has been a growing focus on
conducting fundamental studies through the applicationof appropriate modelling techniques and novel analytical
J Pharm Sci Pharmacol 1 57ndash67 2014 65
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Film Coating Technology Past Present and Future Gaur et al
technologies In addition recent trends are directed towardimprovements in processing as well as development ofnovel release functionality The following section providesa review to some of these areas
PROCESS MODELLING SYSTEMS ANDTHEIR APPLICATIONSFilm coating process comprises various steps which canbe direct or indirect Direct parameters include air pres-sure and flow temperature of coating spray and tabletcore and spray rate The indirect parameters take accountof droplet size distribution and viscosity coating unifor-mity and thickness So different modelling systems havebeen proposed eg Digital video imaging Discrete ele-ment methodologies (DEM) Computational fluid dynam-ics (CFD)Discrete element method embodies different techniques
implying on a large number of small particles to figure outthe movement and their interaction In film coating pro-cedure DEM is used for estimating movement of tabletsand predicting the coating uniformity Computational fluiddynamics applies the principles of fluid mechanics for filmcoating process (Felton and Porter 2013 Felton 2007)The major application of process analytical technique is
that it is amenable to automation So it can be applied formonitoring and controlling various unit operations It canbe applied for product moisture content amount of coatingapplied endpoint of the process and properties of coatingeg porosity and densityHowever adaptation of PAT for coating process requires
positioning of sensors in unsuitable conditions whichcan have a bearing on sensor sensitivity So varioussophisticated analytical processes eg terahertz refractiveindex (TRI) and pulse imaging (TPI) near-infrared andraman spectroscopy (NIR) laser-induced breakdown spec-troscopy (LIBS) and confocal laser techniques can beapplied offline All of these techniques can also be usedonline since these are non-destructive except LIBSNIR methods can be employed for determining the coat-
ing amount to predict drug release rate in combinationwith multivariate analysis NIR spectroscopy can be usedto estimate an API in a coated tablet with plusmn 4 targetvalue in comparison to HPLC Major advantage of NIRspectroscopy is its non-invasiveness and rapidity Howeverit cannot be used with drugs in hydrate form Raman spec-troscopy is less sensitive to hydrates TPI technique can beused to determine the amount of coating in a side-ventedpan (Felton 2007 Felton and Porter 2013)
CONCLUSIONBased on the facts regarding film coating process we canemphasize that various recent trends may drive the indus-try closer to large scale adoption of dry powder coatingtechnologies for oral delivery First the current changes
in global austerity have pushed many pharmaceutical andbiotechnology companies to seriously examine manufac-turing costs The lower cost associated with dry powdercoating technology makes it attractive for both brand andgeneric companies seeking to reduce operating expensesAnother major driver in the future will be the needs of
advanced drug products specifically focused in the area ofcounterfeit resistance and amorphous formulation supportCounterfeit drugs are a major problem facing global phar-maceutical companies with steps being taken to protectthe supply chain and also develop visually differentiatedproducts Dry powder coating particularly electrostatic drypowder coating can be used to prepare novel identificationmarks onto drug products in a rapid cost effective mannerleading to enhanced brand identificationBeyond this the potential to eliminate the need for sol-
vents allows for more effective application of coatings tomoisture sensitive products This opens up unique oppor-tunities in the drug product design of amorphous systemsand may potentially play a role in future product designsGiven the potential of the technology academic researchwill continue in earnest as the pharmaceutical industrycontinues the adoption of the technology Over time anddriven by a number of different factors dry powder coatingappears poised to become a major pharmaceutical coatingtechnology in the future
Acknowledgment The authors wish to express thegratitude towards administrative authorities at ITSParamedical (Pharmacy) College Muradnagar Ghaziabadfor providing necessary support during collection of data
REFERENCESAulton M (ed) (1995) Mechanical properties of film coats Tay-lorampFrancis London
Bodmeier R and Paeratakul O (1994) Mechanical properties of dry andwet cellulosic and acrylic films prepared from aqueous colloidal polymerdispersions used in the coating of solid dosage forms PharmaceuticalResearch 11 882ndash88
Chen W Chang S-Y Kiang S Early W Paruchuri S and DesaiD (2008) The measurement of spray quality for pan coating processJ Pharm Innov 3 3ndash14
Chen W Chang S Y Kiang S Marchut A Lynberg O Wang JRao V Desai D Stamato H and Early W (2010) Modeling of pancoating process Prediction of tablet content uniformity and determinationof critical process parameters J Pharm Sci 99 3213ndash24
Cole G (1998) Pharmaceutical Coating Technology Taylor and FrancisLondon
Dillon R E Matheson L A and Bradford E B (1951) Sintering ofsynthetic latex particles Journal of Colloid Science 6 108ndash17
Felton L A (2007) Characterization of coating systems AAPS PharmSci Tech 8 112
Felton L A and Porter S C (2013) An update on pharmaceutical filmcoating for drug delivery Expert Opinion on Drug Delivery 10 421ndash35
Franz R and Doonan G (1983) Measuring the surface temperature oftablet beds using infrared thermometry Pharm Technol 7 55ndash67
66 J Pharm Sci Pharmacol 1 57ndash67 2014
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Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
Harris M R and Sellassie G (eds) (1997) Aqueous Polymeric Coat-ing for Modified Release Oral Dosage forms Marcel Dekker Inc NeyYork
Hogan J (1998) Pharmaceutical Coating Technology Taylor and FrancisLtd London
Lachman L Lieberman H A and Joseph L K (1989) The Theoryand Practice of Industrial Pharmacy vol 3 Varghese Publishing HouseMumbai
Lehmann K (ed) (1994) Coating of multiparticulates using polymericsolutions Formulation and process considerations Marcel Dekker IncNew York
Libermen H and Lachman L (2003) Pharmaceutical Dosage FormsTablets Marcel Dekker Inc NY Vols 1ndash3
Lipper R D Desai D and Kiang S (September 11ndash12 2006) CaseStudy Implementation of Design Space Concepts in Development of anActive-Coated Tablet In Real World Applications of PAT and QbD inDrug Process Development and Approval Bristol-Myers Squibb Pharma-ceutical Research Institute Arlington Virginia USA
Lippold B C and Monells P P (2001) Film formation reproducibilityof production and curing with respect to release stability of functionalcoatings from aqueous polymer dispersions Pharmazie 56 5ndash17
Malm C J and Waring C E (1937) Cellulose esters containing dicar-boxylic acid groups and process of making the same
Mazer T B Meyer G A Hwang S M Candler E L Drayer LR and Daab-Krzykowski A (1992) System for delivering an activesubstance for sustained release
Narang A K M Castoro J Varia S and Desai D (2011) Effect ofPro- and Anti-Oxidants on the Formation of Formyl Species in PVA- andPEG-Based Tablet Coating Material AAPS Washington D C USA
Narang A S Desai D and Badawy S (2012) Impact of excipientinteractions on solid dosage form stability Pharm Res 29 2660ndash83
Ogaji I and Nnoli O (2010) Film coating potential of okra gum usingparacetamol tablets as a model drug Asian J Pharm 4 130ndash34
Ogaji I J and Hoag S W (2011) Effect of grewia gum as a suspend-ing agent on ibuprofen pediatric formulation AAPS PharmSciTech 12507ndash13
Ogaji I J Okafor I S and Hoag S W (2013) Grewia gum as a poten-tial aqueous film coating agent I Some physicochemical characteristicsof fractions of grewia gum J Pharm Bioall Sci 5 53ndash60
Okutgen E Jordan M Hogan J E and Aulton M E (1991) Effectsof tablet core dimensional instability on the generation of internal stresses
within film coats part II Temperature and relative humidity variationwithin a tablet bed during aqueous film coating in an accela-cota DrugDevelopment and Industrial Pharmacy 17 1191ndash99
Opadryreg Complete Film Coating System Coating ParametersndashAqueous Formulas Colorcon Inc North America BPSI HoldingsLLC
Porter C (1990) Coating of Pharmaceutical Solid Dosage Forms MackPublishing Company Easton Pennsylvania
Porter S C (ed) (2011) Scale-Up of Film Coating Informa HealthcareNew York
Porter S C and Felton L A (2010) Techniques to assess film coat-ings and evaluate film-coated products Drug Development and IndustrialPharmacy 36 128ndash42
Rekhi G S Porter S C and Jambhekar S S (1995) Factors affectingthe release of propranolol hydrochloride from beads coated with aque-ous polymeric dispresions Drug Development and Industrial Pharmacy21 709ndash29
Sadeghi F Ford J L Rubinstein M and Rajabi-Siahboomi A R(2001) Study of drug release from pellets coated with surelease con-taining hydroxypropyl methylcellulose Drug Development and IndustrialPharmacy 27 419ndash30
Savage G V and Rhodes C T (1995) The sustained release coating ofsolid dosage forms A historical review Drug Development and Indus-trial Pharmacy 21 93ndash118
Seitz J A Swarbrick J and Boylan J C (1988) Aqueous film coat-ing Encyclopedia of Pharmaceutical Technology Marcel Dekker NewYork pp 337ndash49
Singh P Solanky T K Mudryya R Pfefferc R and Davea R (2001)Estimation of coating time in the magnetically assisted impaction coatingprocess Powder Technology 121 159ndash67
Syloidreg FP silica excipientsmdashmore than just Silica (Belgium Fred Mon-suur Grace Davison Discovery Sciences) (13 September 2010)
Systems GNP (2012) SUPERCELLtrade Tablet Coating Technology (SCT)Niro Inc 9165 Rumsey Road Columbia MD 21045 USA
Wu C and McGinity J W (2001) Influence of Ibuprofen as a solid-state plasticizer in Eudragit RS 30D on the physicochemical propertiesof coated beads AAPS PharmSciTech 2 1ndash9
Zheng W and McGinity J W (2003) Influence of Eudragit NE 30 Dblended with Eudragit L 30 D-55 on the release of phenylpropanolaminehydrochloride from coated pellets Drug Development and IndustrialPharmacy 29 357ndash66
J Pharm Sci Pharmacol 1 57ndash67 2014 67
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Film Coating Technology Past Present and Future Gaur et al
Figure 1 Chronological development (Decade wise) in coating technology
time possibility of preparing thin smooth continuous coat-ings and reduced risk of hydrolysis (Fig 2)The film formation occurs due to removal of the sol-
vent causing an increase in concentration of polymerresembling a gel However coating with organic solutionsdecreased in popularity due to the restrictions concerninghazardous solvents On the other hand environmental con-cerns and regulatory issues enhanced the production costsdue to solvent recovery (Savage and Rhodes 1995)
Aqueous Based CoatingSolutionsPrimary requirement for the polymer is to be water solu-ble These systems have been used as protective coatingsas they result in water-soluble films without any releasemodifying effects Commonly used hydrophilic polymersare cellulose derivatives such as HPMC however PVPPVA and PEGs are also suitable Small molecular weightpolymers are favoured to optimize the ratio of solid con-tent to viscosity for the coating formulation Optimal inter-action of the polymer can be obtained by the use ofwater-soluble plasticisers eg glycerol propylene glycolor triacetin (Lehmann 1994 Porter 1990)
DispersionsRecently aqueous polymer dispersions are being usedin coating of water-insoluble polymers due to increas-ing concerns about the toxicity of the organic solventsenvironmental pollution and cost-intensive solvent recov-ery systems The size of the polymer particles in thesetwo-phase systems is in the colloidal range with the upperlimit around 1 m to ensure good storage stability Themain property of these dispersions is their low viscositydespite their high solids content which may reach up to30 of the total formulation (Dillon et al 1951)The major problem related to aqueous coating systems
is prolonged processing time due to the higher heat ofvaporization of water however this problem was eradi-cated by modified equipment design such as developmentof side-vented perforated coating pans and fluidized bedequipment for increased drying efficiency Process automa-tion and the concept of validation have resulted in a strongincrease of productivity The film formation from aque-ous colloidal dispersions is a complex multi-step processThe polymer particles are closely packed upon increasingconcentration of the dispersion due to water evaporationIn this ordered arrangement the polymer particles comeinto contact with each other for the first time Further
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Gaur et al Film Coating Technology Past Present and Future
Figure 2 Types of film coating
water loss goes along with a deformation of the particlesforming a denser array (Cole 1998) Dry sintering andcapillary forces are considered as possible mechanisms forthe particle deformation Finally in the last stage of film
formation the individual particles lose their identity afterthe diffusion of polymer chains through the boundary andformation of a continuous film with adequate mechanicalproperties occurs The performance of the resulting film ishighly affected by the temperature during film formationIf the temperature remains above the boiling temperatureof water the vapour pressure during film-formation maybe sufficient to burst the surface film layer causing voidsand pinholes These imperfections may be responsible forhigher water vapour permeability or enhanced drug release(Harris and Sellassie 1997)
Redispersible PowdersThese systems were originally developed for enteric poly-mers which were esters prone to hydrolysis in aque-ous media (Porter 1990) eg Aquateric the commercialredispersible powder of cellulose acetate phthalate (CAP)or redispersible Eudragit L enteric variant of methacrylicacid copolymer (Bodmeier and Paeratakul 1994) Addi-tional advantages of redispersible powder formulations areless propensity for flocculation when exposed to high shearforces or temperature changes reduced storage and ship-ping cost and enhanced microbiological stability Redis-persible polymer powders are usually prepared throughfreeze- or spray drying of polymer dispersions But it isimportant that the properties of the original polymer dis-persions are regained after the redispersion of the polymerpowder especially the original particle size distributionsince an increase in the particle size can affect the filmformation negativelyThe film formation from aqueous dispersion occurs by
coalescence of particles in a continuous film (Fig 3) Thecoalescence of aqueous polymer dispersion is initiated bywater evaporation which pushes dispersed polymer parti-cles into a closely packed ordered array with water filledvoids After the polymer particles come into contact witheach other they deform and fuse in order to coalesce intoa film Coalescence occurs when the promoting forces aregreater than the resistive forces of the particles Film forma-tion ie coalescence is a complex process and depends oncoating and storage conditions coating polymer polymer
Water vaporization
Water vaporization
Aqueous dispersion of coating material depositedon the surface of the tablet
Compaction and deformation of coating materialon the surface of the tablet
Coalescence of coating material on the surface ofthe tabletand form a film
Figure 3 Mechanism of aqueous polymer film formationprocess
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Film Coating Technology Past Present and Future Gaur et al
molecular weight and particle size coating liquid con-stituents and properties like viscosity and surface Sincecoalescence occurs above a minimum film formation tem-perature (MFT) temperature and rate of water evaporationare major process-related factors affecting the properties ofcoatings Usually a thermal after-treatment (curing) is doneto remove the film defects (Aulton 1995 Lachman et al1989)
Process ParametersThe spraying rate affects the moisture content which inturn affects quality and uniformity of the film A low sprayrate will give a brittle film due to incomplete coalescencedue to inadequate wetting and a high spray rate causesover wetting resulting in picking and sticking The sprayrate also interacts with tablet temperature and a low tablettemperature with high spray rate can produce cracks inthe film Increase in pressure reduces the surface rough-ness by producing thin dense film however excessive pres-sure forms very fine droplets which spray dries beforegetting to tablet bed causing spray loss The inlet air tem-perature impacts the drying process and coating unifor-mity High temperature enhances the drying efficiency anddecreases the water penetration however too much air tem-perature can cause premature drying and reduces the effi-ciency Since water is less volatile than organic solventsand requires higher drying capacity resulting in higherenergy cost of the entire coating process Ideal Cures PvtLtd has developed some products (INSTACOAT rangefor example Instacoat EHP 250 Instacoat EMB InstacoatEEN Instacoat EHA Instacoat Aqua Instacoat Aqua IIInstacoat Aqua III and Instacoat P4) which dries faster andthe whole coating process can be completed in the sameor sometimes little less time as compared to organic sol-vent based coatings The increase in rotating speed canimprove the mixing but to a certain level An increase inthe pan speed reduces variation in thickness and enhancesthe coating uniformity however a excessively high speedcan lead to undesired breakage
Air Pressure of AtomisationUsually the drug should be stable to withstand all the pro-cessing parameters as per the specification however it isimportant to consider the properties of the drug There is astrong potential of interaction that can occur between thedrug and polymeric material or any other additive Poly-meric material after atomisation can possibly dissolve theouter layer of the substrate and the components of the lat-ter may also migrate eg migration and subsequent recrys-tallization of propranolol HCl in Eudragit NE 30D filmsso sub-coating is done to overcome this problem as it pre-vents interactions and it is suitable when enteric coatingis being done on an acid-labile drug as enteric coatingpolymers are acidic in nature (Rekhi et al 1995)Size and shape of the substrate is also of consider-
able importance as its movement within the equipment is
deeply influenced A biconvex round tablet is preferred asflat tablets tend to agglomerate during the process Thereare possibilities of shallow convex tablets undergoing abra-sion due to its sharp edges and thus sub-coating becomesessentialSurface wettability is important as wetting and spread-
ing of the polymer material is related to the smoothness ofthe film and adhesion to the substrate Coated multipartic-ulate systems offer several advantages over larger singleunit dosage forms especially when applied to modified-release coatings due to greater uniformity in GI transittime and a reduced potential for premature release Thesecoated particles can be filled into capsules or compressedinto tablets When compressing coated particles the forceused during the tabletting process and the mechanicalstrength of the coating are critical Faster drug release mayoccur if the film cracks or fractures during compactionwhile slower drug release has been reported when the coat-ings fuse together to form a matrix Excipients such asmicrocrystalline cellulose minimize direct contact of thecoated pellets and dissipate the compression forces to pre-vent film fracturePolymeric films adhere to the substrate surface using
two major forces namely the strength of the interfa-cial bonds and the internal stresses within the film Theprimary type of interfacial bonding is hydrogen bond for-mation although dipole and dipole-induced dipole interac-tions also occur Substrate considerations such as surfaceroughness tablet hardness and substrate hydrophobicitycan affect the strength of interfacial bonding In contrastinternal stresses which arise from forces due to shrinkageof the film upon solvent evaporation thermal stress due tothe differences in thermal expansion of the film and thesubstrate and volumetric stress due to swelling during stor-age tend to weaken adhesion Use of excipients with ther-mal expansion coefficients similar to that of the polymercan reduce internal stresses and improve polymer adhesion(Lippold and Monells 2001 Okutgen et al 1991 Franzand Doonan 1983)
Dry CoatingThere are several disadvantages of using the solventswhether aqueous or organic eg drying time and microbi-ological stability for aqueous coating whereas safety andenvironment hazards for organic solvents These issueshave led to the adoption of dry powder coating techniquesin a number of other industries Among these are technolo-gies which range from the atomization of molten materialscommonly known as melt coating to softened powder lay-ering and electrostatic adhesion Types of Dry Coating areas follows (Felton and Porter 2013)
Electrostatic Dry CoatingThis novel coating technique is an alternative to aqueousor solvent based coating process is widely useful in foodtechnology paint technology metal coatings coating of
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Gaur et al Film Coating Technology Past Present and Future
living cells and coating of tablets as well as capsules Theprinciple of electrostatic powder coating states that spray-ing of a mixture of finely grounded particles and polymersonto a substrate surface without using any solvent and thenheating the substrate for curing in oven until the powdermixture is fused into filmAccording to the charging mechanism there are two
types of spraying units namely(a) Corona charging(b) Tribo charging
Magnetically Assisted Impaction CoatingIn this technique the particles are assumed to stay in afluidized state where the distribution of velocities is aMaxwellndashBoltzmann type It is assumed that the collisionsoccurring among the particles are important for impingingthe guest particles onto the surface of host particles therebymaking a transient surface on the host particles The coatingtime depends on various parameters eg properties of thehost and guest particles number of host particles height ofthe fluidized bed and ratio of the host and guest particlesdiameters For a particular coating time the bed height andparticle size should be optimum (Singh et al 2001)
Film Formation Mechanisms inDry Powder CoatingFilm formation takes place by a process of evaporationcoalescence and sintering which are influenced by pro-cess and formulation considerations During the dry pow-der coating process the substrates are often heated abovethe glass transition temperature of the layering materialsso that the coating materials soften and adhere to the sub-strate For conventional film coating spreading and adher-ence is not limited by mobility however powder systemsmay become limited by mobility particularly when liquidlevels are reduced to the point where solid particle defor-mation becomes rate limiting This introduces a series ofconstraints related to mechanical and thermal propertiesof the coating formulation Coalescence and film forma-tion are therefore dependent on these properties as wellAs such glass transition temperature and plastic deforma-tion characteristics of the coating materials are paramountto the success of the process Many pharmaceutical coat-ing materials are amorphous polymers exhibiting a glasstransition temperature related to the change from a glassto a super cooled liquid On transition which occurs at aspecific temperature mobility of the system increases sig-nificantly The greater mobility allows for molecular rear-rangement and alters the plastic deformation characteristicsof the materialsThe mechanism of film formation of the powders lay-
ered onto the solid cores ismdashsummarized as (Felton andPorter 2013 Felton 2007)(i) Coalescence and sintering of the particles of the poly-meric materials in a process that involves the partial fusionof the polymer
(ii) Levelling of the coating material includes densifica-tion of the layer with reduction of the empty spaces andsmoothening of the surface(iii) Cooling of the layer and hardening of the coating
Based on FunctionProtective CoatingsThin films of water soluble polymers are often appliedfor taste or odour masking or to improve the stabilityof moisture sensitive products or for better mechanicalresistance of the product during handling Such protectivecoatings need to remain intact for the short time of swal-lowing and after that they should immediately dissolve toensure immediate drug release These polymers are water-soluble eg cellulose ethers (eg hydroxypropyl methyl-cellulose (HPMC)) polyvinyl acetate (PVA) or polyvinylpyrrolidone (PVP) Eudragitreg E is a methacrylic copoly-mer insoluble in saliva but rapidly dissolves in the acidicpH of the stomach Sometimes enteric polymers eg shel-lac can also be applied at very low concentration whichgives very low film thickness insufficient to provide gastricresistance and disintegrates in the stomach within 30 min(Lehmann 1994 Porter 1990 Porter 2011)
Functional CoatingsFilm coatings which are applied to achieve a desiredrelease profile are usually termed modified-release orfunctional coatings Those intended to protect the drugfrom the acidic environment of the stomach are entericcoatings Extended release coatings in contrast areintended to control the release of the drug over a prolongedperiod of time (Porter 1990)Enteric Coatings Enteric coatings are prepared from
gastric resistant polymers which remain intact in stom-ach but immediately dissolve in small intestine Themost effective enteric polymers contain many carboxylicgroups with a pKa of 3ndash5 Therefore they will dissoci-ate and dissolve only when the pH rises above this value(Porter 2011 Lehmann 1994) Before the synthetic poly-mers were introduced to the market shellac a naturalpolymer was one of the main polymer used for this pur-pose Cellulose acetate phthalate (CAP) was the first syn-thetic polymer described in 1937 which soon gained highpopularity as a gastric resistant polymer Later polyvinylacetate phthalate (PVAP) and hydroxypropyl methylcel-lulose phthalate (HPMCP) were preferred due to theirlower permeability in the gastric fluid and improved sta-bility against hydrolysis Today methacrylate copolymersEudragitreg L and S are two of the most widely used poly-mers for this purpose (Malm and Waring 1937 Zheng andMcGinity 2003)Extended Release Coatings The patient compliance is
usually inversely proportional with the frequency of drugadministration especially when multiple daily administra-tions are necessary to maintain constant blood levels of the
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Film Coating Technology Past Present and Future Gaur et al
drug Therefore extended release polymers were devel-oped which are able to provide a sustained action by acontrolled release over time Waxes and some natural poly-mers were already discovered earlier to be useful to pro-long the drug release if coated onto the solid dosage formsMostly their mechanism of performance is based on slowdegradation or erosion Polymers for extended release arein general insoluble in water over the entire pH range Thedrug release is thus controlled by diffusion through thehydrated polymer or through cracks or water-filled poresThere are still only few polymers available on the mar-ket for extended release eg cellulose acetate ethylcel-lulose or the methacrylic acid copolymers Eudragitreg RSRL and NE Combinations of ethylcellulose with waxeswater-soluble or enteric polymers were investigated toachieve extended drug release for drug with varying oreven pH-dependent solubilities Synthetic polymers how-ever do not fit into the overall product concept of phyto-pharmaceutical products or as for nutraceuticals they arenot approved Therefore several attempts were undertakento achieve sustained drug release by using only naturalpolymers The drug release from silk fibroin coated tabletsafter cross-linking with a carbodiimide was extended toseveral hours (Savage and Rhodes 1995) Shellac is alsoable to provide prolonged drug release at higher coatinglevels or as matrix forming material However there is nodrug release for such systems in the gastric medium due tothe enteric property of shellac Zein as a water-insolublenatural polymer is an alternative for extended drug releaseespecially in combination with an additional enteric top-coat (Mazer et al 1992)
Active CoatingIn it the drug is embedded into the coat to formulate afixed dose combination or to modify the release profileThe beadlets are then filled into capsules however the vol-ume limitation of capsules makes it an unsuitable approachfor higher dose drugs (Seitz et al 1988)This is particularly useful for the drugs unstable at
high mechanical stress In an active coating process com-mon pharmaceutical operations can be avoided Drugs thatundergo acid or base catalysed degradation have been sta-bilized by this technique It gives relatively high drug toexcipient ratio than encapsulating such molecules in thetablet core Fixed dose combinations can be formulated bythis approach (Hogan 1998)The primary concerns of an active coating process
are end-point content uniformity efficiency and stabilitywhich are either directly or indirectly affected by pro-cess parameters such as rate of spraying inlet air temper-ature residual moisture pan speed atomisation pressureand drug properties The end point is estimated by the gainin tablet weight or quantity of coating suspension sprayedPeriodically tablets are sampled and analysed for the drugamount (Lipper et al September 11ndash12 2006) Severalmathematical models have been proposed to ascertain a
correlation between coating parameters and content unifor-mity but the model proposed by Cheng et al has confirmedto be most robust (Chen et al 2010 Chen et al 2008)Coating time is also an important parameter since a
longer coating time results in better content uniformity butit makes the process not amenable for a high volume prod-uct On the other hand too short coating time can lead toincomplete coating process Spray zone width should notbe too narrow or too wide If the tablet bed has not beenappropriately covered then there will be either unsprayedsubstrate or unused deposit of coating solutionCoating process should yield the tablets having required
polymorphic forms and the coating suspension shouldcrystallise after drying The stability is adversely affectedif the coating stays in amorphous state The polymor-phism also depends on coating excipients eg plasticisers(Narang et al 2011 Narang et al 2012 Chen et al 2010Chen et al 2008)Effectiveness of the Active Coating Process The coat-
ing efficiency improves significantly when the droplet sizeis smaller than 10 m By appropriate selection of atomiz-ing and pattern air volume the fraction of droplets smallerthan 10 microns can be reduced to improve the overallefficiency of the coating process Factors governing themsuch as high ratios of the suspension spray rate to atom-ization air flow rate suspension spray rate to pattern airflow rate or atomization air flow rate to pattern air flowrate can improve the coating efficiency
FILM COATING FORMULATIONCOMPONENTSPolymersA polymer is a large molecules made up of many identicalsubunits of monomers (Table I)
Immediate Release Coating PolymersCellulose Derivates The most widely used cellulosic
polymers is Hydroxypropyl Methyl Cellulose (HPMC)which is readily soluble in aqueous medium and forms flex-ible strong films which adhere to the core Other examplesMC (Methyl Cellulose) and HPC (Hydroxypropyl Cellu-lose) (Hogan 1998 Lachman et al 1989 Lehmann 1994)Vinyl Derivates The most widely used vinyl polymer
is Poly Vinyl Pyrrolidone (PVP) however it has inherenttackiness For better film coating its copolymer with vinylacetate is used
Modified Release Coating PolymersExtended Release Coating Polymers They are dis-
solved in organic solvent or dispersed in aqueous mediumeg highly substituted cellulose making them water-insoluble example Ethyl Cellulose (EC)Enteric Coating Polymers
(a) Methacrylic Acid The presence of carboxylic acidgroups renders this class to be insoluble in water at low pH
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Table I Film coatings are available based on the following polymeric materials
pH Independent polymer for rapidly disintegrating film coating
1 Neutral co-polymer Film coat E30D For film coating of tabletspellets granules powders
Natural polymer
1 Xanthan gum Film coating of tablets2 Pectin Film coating of tablets3 Chitosan Film coating of tablets4 Okra gum Film coating of tablets5 Grewia gum Film coating of tablets
(stomach) but as the pH rises towards neutrality in upperpart of the small intestine the coating gradually dissolvesExample Eudragit(b) Phthalate esters These polymers contain free car-boxylic acid making them acid insoluble however in intes-tine they become deprotonated and dissolves in basicmedia They are also called enteric coating polymers egCellulose acetate phthalate (CAP) Enteric coating poly-mers can be classified into 3 groups based on chemicalcompositions as listed below
The solubility of the polymers depend on the numberof carboxylic acid groups Enteric formulations shouldhave less than 10 drug release in 2 hours during acidstage The completion of the drug release in the continu-ation testing in the buffer stage should take place within45 min Classification of Polymers Based on Derivatives(Lehmann 1994 Libermen and Lachman 2003 Malm
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Film Coating Technology Past Present and Future Gaur et al
and Waring 1937 Sadeghi et al 2001 Ogaji and Nnoli2010 Ogaji and Hoag 2011 Ogaji et al 2013)
PlasticizersPlasticizers are relatively low molecular weight materialswhich are used as additives in pharmaceutical coating for-mulations to reduce the brittleness and increase the flex-ibility of the resulting film They act by weakening intermolecular attraction between polymer chains and facili-tating coalescence of discrete polymer spheres of aque-ous dispersed systems during film formation Adhesive andmechanical properties of the coating and subsequent drugrelease are dependent on the concentration of plasticizersto a great extent Plasticizers are non volatile componentsand therefore are responsible for the weight gain of dosageforms during coating A plasticizer has to be miscible andfulfil all the compatibility parameters with the polymerbeing usedAn important consideration is the content of plasticizer
as it can affect the glass transition temperature (Tg) soit should be experimentally determined by evaluating thechanges in Tg of polymer as the plasticizer content isincreased Tg is the temperature for amorphous polymersat which the behaviour of the film changes from hard andbrittle to soft and elastic An effective plasticizing agentis one which exhibits a greater decrease in the Tg of thefilm Changes in the mechanical properties of the poly-meric film are an indication of plasticizer efficacy (Seitzet al 1988 Wu and McGinity 2001)Plasticizers are classified into three groups
Anti-AdherentsAnti-adherents are used as additives to avoid agglomera-tion of the substrates during both the coating process andon subsequent storage One of the most common anti-adherents used in pharmaceutical coatings is talc but sinceit has to be used at high concentration it creates pro-cessing challenges including clogging of the spray noz-zle during coating and particle sedimentation It tends todecrease water vapour permeability and also the dissolu-tion rate of drugs due to its hydrophobic nature It alsoaffects the mechanical and adhesive properties of polymerfilms so now Glyceryl monostearate has been found as analternative to talc
Opacifying AgentsColorantsPigments deliver elegance and stability enhancement tothe solid dosage form Water-insoluble lakes and the iron
oxides are most commonly used pigments Colour migra-tion and stability issues have diminished the use of thewater-soluble dyes in film coating Pigments can signifi-cantly affect the mechanical and permeability properties ofthe film An inverse relation-ship between film-tablet adhe-sion and the particle size of the pigment has been reportedStudies have shown that the shape of the pigment par-ticle and the extent of polymer-particle interaction influ-ence the elastic modulus of polymeric films and surfacepolarity of pigments influences drug release In additionchemical incompatibilities between the pigment and thepolymer have also been reported predominantly relatedto the size and surface charge of the components andthe pH of the medium One important concept relevantto pigments is the critical pigment volume concentration(CPVC) this is the maximum concentration (based on vol-ume) of the insoluble material that can be incorporated intoa film without compromising film properties If the CPVCis exceeded insufficient polymer is present to surroundall the insoluble particles resulting in marked changes indifferent properties of the film Colorants are mainly clas-sified in to three types(i) Organic dyes and their lakes eg Erythrosine tar-trazine Sunset yellow(ii) Inorganic colours eg Iron oxide yellow red andblack titanium dioxide talc(iii) Natural colours eg Riboflavin Anthocyanins andCarmine
SolventsVehiclesThe key function of a solvent system is to dissolve ordisperse the polymers and other additivesThe major classes of solvents being used are aqueous
(Water) and Nonaqueous (Alcohols Ketones Esters Chlo-rinated hydrocarbons) Because of environmental and eco-nomic concerns water is the most commonly used solvent
Miscellaneous Coating Solution ComponentsSolid dosage form may be incorporated with several spe-cial materials such asFlavours and sweeteners are added to mask unpleasant
odours or to develop the taste eg fruit spirits (organicsolvent) aspartame water soluble pineapple flavourSurfactants are ancillary to stabilize immiscible or insol-
uble ingredients in the coating They facilitate substratewettability and promote coalescence of polymeric materialover the substratersquos surface eg Spans Tweens etcAntioxidants are incorporated to stabilize a dye system
to oxidation and colour change eg oximes phenols etcAntimicrobials are added to inhibit microbial growth
in the coating composition Various cellulosic materialsare mainly prone to microbial growth and they can notbe stored in solution form eg Carbamates alkylisothia-zloinone benzothiazoles etc
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Gaur et al Film Coating Technology Past Present and Future
CURRENT TRENDS IN FILM COATING ANDFUTURE DIRECTIONSOpadry formulations provided numerous advantages ver-sus the use of individual raw materials including thereduction of the number of raw materials for Qualitycontrol testing reduced preparation time reliable colour-matched formulations tremendous appearance and excel-lent mechanical parameters However opadry dispersionsolids must be stored as 10ndash15 ww aqueous solution toattain workable 300ndash600 centipoises viscosityOpadry II category consisting HPMC and polysaccha-
rides was introduced to increase productivity The mostsignificant recent advances in the development of fully for-mulated aqueous film coatings have been the introductionof new film coatings based on polyvinyl alcohol (PVA)and sodium carboxymethylcellulose (NaCMC) PVA-basedfilms are known to have relatively low permeability formoisture vapour and oxygen whereas NaCMC-based coat-ings are glossy and have low oxygen permeability andrelatively high permeability for water vapourOpadry aqueous moisture barrier (AMB) and Opadry II
85 series are two proprietary families of PVA-based prod-ucts that were commercialized in the mid to-late 1990sThe Opadry AMB formulation were optimized to providethe lowest moisture vapour transmission rate Opadry II85 products give moisture vapour transmission rate almostas low as Opadry AMB but can be applied at significantlyhigher spray ratesFilm coatings based on PVA and NaCMC offer various
advantages Now moisture-sensitive drugs can be coatedin an aqueous coating process by PVA-based coatingsNaCMC based coatings provide demonstrable oxygenbarrier properties and excellent aesthetic characteristics(Porter and Felton 2010)
Supercelltrade Coating TechnologyThe ldquostandardrdquo practice of tablet coating often delivers anon-homogenous product Because the tablets are loadedin large rotating pans and vented for hot air drying edgesof tablets can get grounded off and intagliation can getfilled in by coating material leading to uneven coating onedgescorners and tablet faces This inaccuracy limits theuse of modified release coatings In a laboratory it is nec-essary to coat several kilograms of tablets at one timemaking RampD of a tablet dosage form costly and difficultFurther extremely hygroscopic as well as flat or other
oddly shaped tablets cannot be coated using present tech-nology so SCT (Niro Pharma Systems) technology uses asmall modular design that accurately deposits controlledamounts of coating materials on friable and extremelyhygroscopic tablets SCTrsquos continuous small-batch capablecoating process is predictable and efficient In SCT thetablets are coated in batches ranging from 30 to 120 gramswhich linearly scale up to production capacity In this tech-nique the tablets are covered with the polymer spray in
the same direction as the hot air resulting in an efficientprocess Due to SCTrsquos unique air distribution plate designthe tablets move very quickly and predictably through thespray zone receiving only a small amount of coating perpass and therefore achieving higher coating accuracy Theprocess time is short in seconds or in minutes as opposedto hours and therefore gentler on the tablets (Systems2012)Supercelltrade Coating Technology may also be used for
coating of flat or highly oblong tablets or friable tabletsIn this process drying is very fast making it possible tocoat extremely hygroscopic tablets The deposition accu-racy is sufficiently high to layer API onto tablets and uni-form layers of taste masking or modified release coatingscan be applied consecutively within a single continuousbatchUnique features of super cell coating technology are
(1) Continuous coating(2) Short processing time(3) Flexible modular design(4) No scale-up to parameters(5) Batch size for RampD (Minimum size sim30 grams)(6) Enhancing technology(7) Multi-layer coating(8) Low humidity process suitable for moisture sensitivematerials
Syloidreg FP Silicas inPharmaceutical Film CoatingsRecently film coatings have also shown encouragingresults to enable the oral delivery of peptide therapeuticsSyloidreg FP silicas have been used as excipients in manypharmaceutical formulations due to their unique morphol-ogy The combined adsorption capacity porosity particlesize and greater surface area allow them to provide severalbenefits simultaneously which can expedite manufacturingand improve efficacy of the final dosage form Syloidreg FPsilica can be used in polymeric coating systems in combi-nation of vinylcellulose or acrylic polymers (13 Septem-ber 2010)In standard concentrationsmdashAddition of Syloidreg 244FP
silica to film coating provides following advantages-Improved spray propertiesElimination of the need for talcImprovement of suspension propertiesPrevention of valve cloggingMinimal settling in spray linesSmoothen tablet surfaceReduction of adhesionApplications Anti-tacking agent Oral peptide deliveryODT formulations Enteric coatings Sustained releasecoatings Controlled release coatings (Grace Discovery)In recent years there has been a growing focus on
conducting fundamental studies through the applicationof appropriate modelling techniques and novel analytical
J Pharm Sci Pharmacol 1 57ndash67 2014 65
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Film Coating Technology Past Present and Future Gaur et al
technologies In addition recent trends are directed towardimprovements in processing as well as development ofnovel release functionality The following section providesa review to some of these areas
PROCESS MODELLING SYSTEMS ANDTHEIR APPLICATIONSFilm coating process comprises various steps which canbe direct or indirect Direct parameters include air pres-sure and flow temperature of coating spray and tabletcore and spray rate The indirect parameters take accountof droplet size distribution and viscosity coating unifor-mity and thickness So different modelling systems havebeen proposed eg Digital video imaging Discrete ele-ment methodologies (DEM) Computational fluid dynam-ics (CFD)Discrete element method embodies different techniques
implying on a large number of small particles to figure outthe movement and their interaction In film coating pro-cedure DEM is used for estimating movement of tabletsand predicting the coating uniformity Computational fluiddynamics applies the principles of fluid mechanics for filmcoating process (Felton and Porter 2013 Felton 2007)The major application of process analytical technique is
that it is amenable to automation So it can be applied formonitoring and controlling various unit operations It canbe applied for product moisture content amount of coatingapplied endpoint of the process and properties of coatingeg porosity and densityHowever adaptation of PAT for coating process requires
positioning of sensors in unsuitable conditions whichcan have a bearing on sensor sensitivity So varioussophisticated analytical processes eg terahertz refractiveindex (TRI) and pulse imaging (TPI) near-infrared andraman spectroscopy (NIR) laser-induced breakdown spec-troscopy (LIBS) and confocal laser techniques can beapplied offline All of these techniques can also be usedonline since these are non-destructive except LIBSNIR methods can be employed for determining the coat-
ing amount to predict drug release rate in combinationwith multivariate analysis NIR spectroscopy can be usedto estimate an API in a coated tablet with plusmn 4 targetvalue in comparison to HPLC Major advantage of NIRspectroscopy is its non-invasiveness and rapidity Howeverit cannot be used with drugs in hydrate form Raman spec-troscopy is less sensitive to hydrates TPI technique can beused to determine the amount of coating in a side-ventedpan (Felton 2007 Felton and Porter 2013)
CONCLUSIONBased on the facts regarding film coating process we canemphasize that various recent trends may drive the indus-try closer to large scale adoption of dry powder coatingtechnologies for oral delivery First the current changes
in global austerity have pushed many pharmaceutical andbiotechnology companies to seriously examine manufac-turing costs The lower cost associated with dry powdercoating technology makes it attractive for both brand andgeneric companies seeking to reduce operating expensesAnother major driver in the future will be the needs of
advanced drug products specifically focused in the area ofcounterfeit resistance and amorphous formulation supportCounterfeit drugs are a major problem facing global phar-maceutical companies with steps being taken to protectthe supply chain and also develop visually differentiatedproducts Dry powder coating particularly electrostatic drypowder coating can be used to prepare novel identificationmarks onto drug products in a rapid cost effective mannerleading to enhanced brand identificationBeyond this the potential to eliminate the need for sol-
vents allows for more effective application of coatings tomoisture sensitive products This opens up unique oppor-tunities in the drug product design of amorphous systemsand may potentially play a role in future product designsGiven the potential of the technology academic researchwill continue in earnest as the pharmaceutical industrycontinues the adoption of the technology Over time anddriven by a number of different factors dry powder coatingappears poised to become a major pharmaceutical coatingtechnology in the future
Acknowledgment The authors wish to express thegratitude towards administrative authorities at ITSParamedical (Pharmacy) College Muradnagar Ghaziabadfor providing necessary support during collection of data
REFERENCESAulton M (ed) (1995) Mechanical properties of film coats Tay-lorampFrancis London
Bodmeier R and Paeratakul O (1994) Mechanical properties of dry andwet cellulosic and acrylic films prepared from aqueous colloidal polymerdispersions used in the coating of solid dosage forms PharmaceuticalResearch 11 882ndash88
Chen W Chang S-Y Kiang S Early W Paruchuri S and DesaiD (2008) The measurement of spray quality for pan coating processJ Pharm Innov 3 3ndash14
Chen W Chang S Y Kiang S Marchut A Lynberg O Wang JRao V Desai D Stamato H and Early W (2010) Modeling of pancoating process Prediction of tablet content uniformity and determinationof critical process parameters J Pharm Sci 99 3213ndash24
Cole G (1998) Pharmaceutical Coating Technology Taylor and FrancisLondon
Dillon R E Matheson L A and Bradford E B (1951) Sintering ofsynthetic latex particles Journal of Colloid Science 6 108ndash17
Felton L A (2007) Characterization of coating systems AAPS PharmSci Tech 8 112
Felton L A and Porter S C (2013) An update on pharmaceutical filmcoating for drug delivery Expert Opinion on Drug Delivery 10 421ndash35
Franz R and Doonan G (1983) Measuring the surface temperature oftablet beds using infrared thermometry Pharm Technol 7 55ndash67
66 J Pharm Sci Pharmacol 1 57ndash67 2014
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Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
Harris M R and Sellassie G (eds) (1997) Aqueous Polymeric Coat-ing for Modified Release Oral Dosage forms Marcel Dekker Inc NeyYork
Hogan J (1998) Pharmaceutical Coating Technology Taylor and FrancisLtd London
Lachman L Lieberman H A and Joseph L K (1989) The Theoryand Practice of Industrial Pharmacy vol 3 Varghese Publishing HouseMumbai
Lehmann K (ed) (1994) Coating of multiparticulates using polymericsolutions Formulation and process considerations Marcel Dekker IncNew York
Libermen H and Lachman L (2003) Pharmaceutical Dosage FormsTablets Marcel Dekker Inc NY Vols 1ndash3
Lipper R D Desai D and Kiang S (September 11ndash12 2006) CaseStudy Implementation of Design Space Concepts in Development of anActive-Coated Tablet In Real World Applications of PAT and QbD inDrug Process Development and Approval Bristol-Myers Squibb Pharma-ceutical Research Institute Arlington Virginia USA
Lippold B C and Monells P P (2001) Film formation reproducibilityof production and curing with respect to release stability of functionalcoatings from aqueous polymer dispersions Pharmazie 56 5ndash17
Malm C J and Waring C E (1937) Cellulose esters containing dicar-boxylic acid groups and process of making the same
Mazer T B Meyer G A Hwang S M Candler E L Drayer LR and Daab-Krzykowski A (1992) System for delivering an activesubstance for sustained release
Narang A K M Castoro J Varia S and Desai D (2011) Effect ofPro- and Anti-Oxidants on the Formation of Formyl Species in PVA- andPEG-Based Tablet Coating Material AAPS Washington D C USA
Narang A S Desai D and Badawy S (2012) Impact of excipientinteractions on solid dosage form stability Pharm Res 29 2660ndash83
Ogaji I and Nnoli O (2010) Film coating potential of okra gum usingparacetamol tablets as a model drug Asian J Pharm 4 130ndash34
Ogaji I J and Hoag S W (2011) Effect of grewia gum as a suspend-ing agent on ibuprofen pediatric formulation AAPS PharmSciTech 12507ndash13
Ogaji I J Okafor I S and Hoag S W (2013) Grewia gum as a poten-tial aqueous film coating agent I Some physicochemical characteristicsof fractions of grewia gum J Pharm Bioall Sci 5 53ndash60
Okutgen E Jordan M Hogan J E and Aulton M E (1991) Effectsof tablet core dimensional instability on the generation of internal stresses
within film coats part II Temperature and relative humidity variationwithin a tablet bed during aqueous film coating in an accela-cota DrugDevelopment and Industrial Pharmacy 17 1191ndash99
Opadryreg Complete Film Coating System Coating ParametersndashAqueous Formulas Colorcon Inc North America BPSI HoldingsLLC
Porter C (1990) Coating of Pharmaceutical Solid Dosage Forms MackPublishing Company Easton Pennsylvania
Porter S C (ed) (2011) Scale-Up of Film Coating Informa HealthcareNew York
Porter S C and Felton L A (2010) Techniques to assess film coat-ings and evaluate film-coated products Drug Development and IndustrialPharmacy 36 128ndash42
Rekhi G S Porter S C and Jambhekar S S (1995) Factors affectingthe release of propranolol hydrochloride from beads coated with aque-ous polymeric dispresions Drug Development and Industrial Pharmacy21 709ndash29
Sadeghi F Ford J L Rubinstein M and Rajabi-Siahboomi A R(2001) Study of drug release from pellets coated with surelease con-taining hydroxypropyl methylcellulose Drug Development and IndustrialPharmacy 27 419ndash30
Savage G V and Rhodes C T (1995) The sustained release coating ofsolid dosage forms A historical review Drug Development and Indus-trial Pharmacy 21 93ndash118
Seitz J A Swarbrick J and Boylan J C (1988) Aqueous film coat-ing Encyclopedia of Pharmaceutical Technology Marcel Dekker NewYork pp 337ndash49
Singh P Solanky T K Mudryya R Pfefferc R and Davea R (2001)Estimation of coating time in the magnetically assisted impaction coatingprocess Powder Technology 121 159ndash67
Syloidreg FP silica excipientsmdashmore than just Silica (Belgium Fred Mon-suur Grace Davison Discovery Sciences) (13 September 2010)
Systems GNP (2012) SUPERCELLtrade Tablet Coating Technology (SCT)Niro Inc 9165 Rumsey Road Columbia MD 21045 USA
Wu C and McGinity J W (2001) Influence of Ibuprofen as a solid-state plasticizer in Eudragit RS 30D on the physicochemical propertiesof coated beads AAPS PharmSciTech 2 1ndash9
Zheng W and McGinity J W (2003) Influence of Eudragit NE 30 Dblended with Eudragit L 30 D-55 on the release of phenylpropanolaminehydrochloride from coated pellets Drug Development and IndustrialPharmacy 29 357ndash66
J Pharm Sci Pharmacol 1 57ndash67 2014 67
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Gaur et al Film Coating Technology Past Present and Future
Figure 2 Types of film coating
water loss goes along with a deformation of the particlesforming a denser array (Cole 1998) Dry sintering andcapillary forces are considered as possible mechanisms forthe particle deformation Finally in the last stage of film
formation the individual particles lose their identity afterthe diffusion of polymer chains through the boundary andformation of a continuous film with adequate mechanicalproperties occurs The performance of the resulting film ishighly affected by the temperature during film formationIf the temperature remains above the boiling temperatureof water the vapour pressure during film-formation maybe sufficient to burst the surface film layer causing voidsand pinholes These imperfections may be responsible forhigher water vapour permeability or enhanced drug release(Harris and Sellassie 1997)
Redispersible PowdersThese systems were originally developed for enteric poly-mers which were esters prone to hydrolysis in aque-ous media (Porter 1990) eg Aquateric the commercialredispersible powder of cellulose acetate phthalate (CAP)or redispersible Eudragit L enteric variant of methacrylicacid copolymer (Bodmeier and Paeratakul 1994) Addi-tional advantages of redispersible powder formulations areless propensity for flocculation when exposed to high shearforces or temperature changes reduced storage and ship-ping cost and enhanced microbiological stability Redis-persible polymer powders are usually prepared throughfreeze- or spray drying of polymer dispersions But it isimportant that the properties of the original polymer dis-persions are regained after the redispersion of the polymerpowder especially the original particle size distributionsince an increase in the particle size can affect the filmformation negativelyThe film formation from aqueous dispersion occurs by
coalescence of particles in a continuous film (Fig 3) Thecoalescence of aqueous polymer dispersion is initiated bywater evaporation which pushes dispersed polymer parti-cles into a closely packed ordered array with water filledvoids After the polymer particles come into contact witheach other they deform and fuse in order to coalesce intoa film Coalescence occurs when the promoting forces aregreater than the resistive forces of the particles Film forma-tion ie coalescence is a complex process and depends oncoating and storage conditions coating polymer polymer
Water vaporization
Water vaporization
Aqueous dispersion of coating material depositedon the surface of the tablet
Compaction and deformation of coating materialon the surface of the tablet
Coalescence of coating material on the surface ofthe tabletand form a film
Figure 3 Mechanism of aqueous polymer film formationprocess
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Film Coating Technology Past Present and Future Gaur et al
molecular weight and particle size coating liquid con-stituents and properties like viscosity and surface Sincecoalescence occurs above a minimum film formation tem-perature (MFT) temperature and rate of water evaporationare major process-related factors affecting the properties ofcoatings Usually a thermal after-treatment (curing) is doneto remove the film defects (Aulton 1995 Lachman et al1989)
Process ParametersThe spraying rate affects the moisture content which inturn affects quality and uniformity of the film A low sprayrate will give a brittle film due to incomplete coalescencedue to inadequate wetting and a high spray rate causesover wetting resulting in picking and sticking The sprayrate also interacts with tablet temperature and a low tablettemperature with high spray rate can produce cracks inthe film Increase in pressure reduces the surface rough-ness by producing thin dense film however excessive pres-sure forms very fine droplets which spray dries beforegetting to tablet bed causing spray loss The inlet air tem-perature impacts the drying process and coating unifor-mity High temperature enhances the drying efficiency anddecreases the water penetration however too much air tem-perature can cause premature drying and reduces the effi-ciency Since water is less volatile than organic solventsand requires higher drying capacity resulting in higherenergy cost of the entire coating process Ideal Cures PvtLtd has developed some products (INSTACOAT rangefor example Instacoat EHP 250 Instacoat EMB InstacoatEEN Instacoat EHA Instacoat Aqua Instacoat Aqua IIInstacoat Aqua III and Instacoat P4) which dries faster andthe whole coating process can be completed in the sameor sometimes little less time as compared to organic sol-vent based coatings The increase in rotating speed canimprove the mixing but to a certain level An increase inthe pan speed reduces variation in thickness and enhancesthe coating uniformity however a excessively high speedcan lead to undesired breakage
Air Pressure of AtomisationUsually the drug should be stable to withstand all the pro-cessing parameters as per the specification however it isimportant to consider the properties of the drug There is astrong potential of interaction that can occur between thedrug and polymeric material or any other additive Poly-meric material after atomisation can possibly dissolve theouter layer of the substrate and the components of the lat-ter may also migrate eg migration and subsequent recrys-tallization of propranolol HCl in Eudragit NE 30D filmsso sub-coating is done to overcome this problem as it pre-vents interactions and it is suitable when enteric coatingis being done on an acid-labile drug as enteric coatingpolymers are acidic in nature (Rekhi et al 1995)Size and shape of the substrate is also of consider-
able importance as its movement within the equipment is
deeply influenced A biconvex round tablet is preferred asflat tablets tend to agglomerate during the process Thereare possibilities of shallow convex tablets undergoing abra-sion due to its sharp edges and thus sub-coating becomesessentialSurface wettability is important as wetting and spread-
ing of the polymer material is related to the smoothness ofthe film and adhesion to the substrate Coated multipartic-ulate systems offer several advantages over larger singleunit dosage forms especially when applied to modified-release coatings due to greater uniformity in GI transittime and a reduced potential for premature release Thesecoated particles can be filled into capsules or compressedinto tablets When compressing coated particles the forceused during the tabletting process and the mechanicalstrength of the coating are critical Faster drug release mayoccur if the film cracks or fractures during compactionwhile slower drug release has been reported when the coat-ings fuse together to form a matrix Excipients such asmicrocrystalline cellulose minimize direct contact of thecoated pellets and dissipate the compression forces to pre-vent film fracturePolymeric films adhere to the substrate surface using
two major forces namely the strength of the interfa-cial bonds and the internal stresses within the film Theprimary type of interfacial bonding is hydrogen bond for-mation although dipole and dipole-induced dipole interac-tions also occur Substrate considerations such as surfaceroughness tablet hardness and substrate hydrophobicitycan affect the strength of interfacial bonding In contrastinternal stresses which arise from forces due to shrinkageof the film upon solvent evaporation thermal stress due tothe differences in thermal expansion of the film and thesubstrate and volumetric stress due to swelling during stor-age tend to weaken adhesion Use of excipients with ther-mal expansion coefficients similar to that of the polymercan reduce internal stresses and improve polymer adhesion(Lippold and Monells 2001 Okutgen et al 1991 Franzand Doonan 1983)
Dry CoatingThere are several disadvantages of using the solventswhether aqueous or organic eg drying time and microbi-ological stability for aqueous coating whereas safety andenvironment hazards for organic solvents These issueshave led to the adoption of dry powder coating techniquesin a number of other industries Among these are technolo-gies which range from the atomization of molten materialscommonly known as melt coating to softened powder lay-ering and electrostatic adhesion Types of Dry Coating areas follows (Felton and Porter 2013)
Electrostatic Dry CoatingThis novel coating technique is an alternative to aqueousor solvent based coating process is widely useful in foodtechnology paint technology metal coatings coating of
60 J Pharm Sci Pharmacol 1 57ndash67 2014
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Gaur et al Film Coating Technology Past Present and Future
living cells and coating of tablets as well as capsules Theprinciple of electrostatic powder coating states that spray-ing of a mixture of finely grounded particles and polymersonto a substrate surface without using any solvent and thenheating the substrate for curing in oven until the powdermixture is fused into filmAccording to the charging mechanism there are two
types of spraying units namely(a) Corona charging(b) Tribo charging
Magnetically Assisted Impaction CoatingIn this technique the particles are assumed to stay in afluidized state where the distribution of velocities is aMaxwellndashBoltzmann type It is assumed that the collisionsoccurring among the particles are important for impingingthe guest particles onto the surface of host particles therebymaking a transient surface on the host particles The coatingtime depends on various parameters eg properties of thehost and guest particles number of host particles height ofthe fluidized bed and ratio of the host and guest particlesdiameters For a particular coating time the bed height andparticle size should be optimum (Singh et al 2001)
Film Formation Mechanisms inDry Powder CoatingFilm formation takes place by a process of evaporationcoalescence and sintering which are influenced by pro-cess and formulation considerations During the dry pow-der coating process the substrates are often heated abovethe glass transition temperature of the layering materialsso that the coating materials soften and adhere to the sub-strate For conventional film coating spreading and adher-ence is not limited by mobility however powder systemsmay become limited by mobility particularly when liquidlevels are reduced to the point where solid particle defor-mation becomes rate limiting This introduces a series ofconstraints related to mechanical and thermal propertiesof the coating formulation Coalescence and film forma-tion are therefore dependent on these properties as wellAs such glass transition temperature and plastic deforma-tion characteristics of the coating materials are paramountto the success of the process Many pharmaceutical coat-ing materials are amorphous polymers exhibiting a glasstransition temperature related to the change from a glassto a super cooled liquid On transition which occurs at aspecific temperature mobility of the system increases sig-nificantly The greater mobility allows for molecular rear-rangement and alters the plastic deformation characteristicsof the materialsThe mechanism of film formation of the powders lay-
ered onto the solid cores ismdashsummarized as (Felton andPorter 2013 Felton 2007)(i) Coalescence and sintering of the particles of the poly-meric materials in a process that involves the partial fusionof the polymer
(ii) Levelling of the coating material includes densifica-tion of the layer with reduction of the empty spaces andsmoothening of the surface(iii) Cooling of the layer and hardening of the coating
Based on FunctionProtective CoatingsThin films of water soluble polymers are often appliedfor taste or odour masking or to improve the stabilityof moisture sensitive products or for better mechanicalresistance of the product during handling Such protectivecoatings need to remain intact for the short time of swal-lowing and after that they should immediately dissolve toensure immediate drug release These polymers are water-soluble eg cellulose ethers (eg hydroxypropyl methyl-cellulose (HPMC)) polyvinyl acetate (PVA) or polyvinylpyrrolidone (PVP) Eudragitreg E is a methacrylic copoly-mer insoluble in saliva but rapidly dissolves in the acidicpH of the stomach Sometimes enteric polymers eg shel-lac can also be applied at very low concentration whichgives very low film thickness insufficient to provide gastricresistance and disintegrates in the stomach within 30 min(Lehmann 1994 Porter 1990 Porter 2011)
Functional CoatingsFilm coatings which are applied to achieve a desiredrelease profile are usually termed modified-release orfunctional coatings Those intended to protect the drugfrom the acidic environment of the stomach are entericcoatings Extended release coatings in contrast areintended to control the release of the drug over a prolongedperiod of time (Porter 1990)Enteric Coatings Enteric coatings are prepared from
gastric resistant polymers which remain intact in stom-ach but immediately dissolve in small intestine Themost effective enteric polymers contain many carboxylicgroups with a pKa of 3ndash5 Therefore they will dissoci-ate and dissolve only when the pH rises above this value(Porter 2011 Lehmann 1994) Before the synthetic poly-mers were introduced to the market shellac a naturalpolymer was one of the main polymer used for this pur-pose Cellulose acetate phthalate (CAP) was the first syn-thetic polymer described in 1937 which soon gained highpopularity as a gastric resistant polymer Later polyvinylacetate phthalate (PVAP) and hydroxypropyl methylcel-lulose phthalate (HPMCP) were preferred due to theirlower permeability in the gastric fluid and improved sta-bility against hydrolysis Today methacrylate copolymersEudragitreg L and S are two of the most widely used poly-mers for this purpose (Malm and Waring 1937 Zheng andMcGinity 2003)Extended Release Coatings The patient compliance is
usually inversely proportional with the frequency of drugadministration especially when multiple daily administra-tions are necessary to maintain constant blood levels of the
J Pharm Sci Pharmacol 1 57ndash67 2014 61
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Film Coating Technology Past Present and Future Gaur et al
drug Therefore extended release polymers were devel-oped which are able to provide a sustained action by acontrolled release over time Waxes and some natural poly-mers were already discovered earlier to be useful to pro-long the drug release if coated onto the solid dosage formsMostly their mechanism of performance is based on slowdegradation or erosion Polymers for extended release arein general insoluble in water over the entire pH range Thedrug release is thus controlled by diffusion through thehydrated polymer or through cracks or water-filled poresThere are still only few polymers available on the mar-ket for extended release eg cellulose acetate ethylcel-lulose or the methacrylic acid copolymers Eudragitreg RSRL and NE Combinations of ethylcellulose with waxeswater-soluble or enteric polymers were investigated toachieve extended drug release for drug with varying oreven pH-dependent solubilities Synthetic polymers how-ever do not fit into the overall product concept of phyto-pharmaceutical products or as for nutraceuticals they arenot approved Therefore several attempts were undertakento achieve sustained drug release by using only naturalpolymers The drug release from silk fibroin coated tabletsafter cross-linking with a carbodiimide was extended toseveral hours (Savage and Rhodes 1995) Shellac is alsoable to provide prolonged drug release at higher coatinglevels or as matrix forming material However there is nodrug release for such systems in the gastric medium due tothe enteric property of shellac Zein as a water-insolublenatural polymer is an alternative for extended drug releaseespecially in combination with an additional enteric top-coat (Mazer et al 1992)
Active CoatingIn it the drug is embedded into the coat to formulate afixed dose combination or to modify the release profileThe beadlets are then filled into capsules however the vol-ume limitation of capsules makes it an unsuitable approachfor higher dose drugs (Seitz et al 1988)This is particularly useful for the drugs unstable at
high mechanical stress In an active coating process com-mon pharmaceutical operations can be avoided Drugs thatundergo acid or base catalysed degradation have been sta-bilized by this technique It gives relatively high drug toexcipient ratio than encapsulating such molecules in thetablet core Fixed dose combinations can be formulated bythis approach (Hogan 1998)The primary concerns of an active coating process
are end-point content uniformity efficiency and stabilitywhich are either directly or indirectly affected by pro-cess parameters such as rate of spraying inlet air temper-ature residual moisture pan speed atomisation pressureand drug properties The end point is estimated by the gainin tablet weight or quantity of coating suspension sprayedPeriodically tablets are sampled and analysed for the drugamount (Lipper et al September 11ndash12 2006) Severalmathematical models have been proposed to ascertain a
correlation between coating parameters and content unifor-mity but the model proposed by Cheng et al has confirmedto be most robust (Chen et al 2010 Chen et al 2008)Coating time is also an important parameter since a
longer coating time results in better content uniformity butit makes the process not amenable for a high volume prod-uct On the other hand too short coating time can lead toincomplete coating process Spray zone width should notbe too narrow or too wide If the tablet bed has not beenappropriately covered then there will be either unsprayedsubstrate or unused deposit of coating solutionCoating process should yield the tablets having required
polymorphic forms and the coating suspension shouldcrystallise after drying The stability is adversely affectedif the coating stays in amorphous state The polymor-phism also depends on coating excipients eg plasticisers(Narang et al 2011 Narang et al 2012 Chen et al 2010Chen et al 2008)Effectiveness of the Active Coating Process The coat-
ing efficiency improves significantly when the droplet sizeis smaller than 10 m By appropriate selection of atomiz-ing and pattern air volume the fraction of droplets smallerthan 10 microns can be reduced to improve the overallefficiency of the coating process Factors governing themsuch as high ratios of the suspension spray rate to atom-ization air flow rate suspension spray rate to pattern airflow rate or atomization air flow rate to pattern air flowrate can improve the coating efficiency
FILM COATING FORMULATIONCOMPONENTSPolymersA polymer is a large molecules made up of many identicalsubunits of monomers (Table I)
Immediate Release Coating PolymersCellulose Derivates The most widely used cellulosic
polymers is Hydroxypropyl Methyl Cellulose (HPMC)which is readily soluble in aqueous medium and forms flex-ible strong films which adhere to the core Other examplesMC (Methyl Cellulose) and HPC (Hydroxypropyl Cellu-lose) (Hogan 1998 Lachman et al 1989 Lehmann 1994)Vinyl Derivates The most widely used vinyl polymer
is Poly Vinyl Pyrrolidone (PVP) however it has inherenttackiness For better film coating its copolymer with vinylacetate is used
Modified Release Coating PolymersExtended Release Coating Polymers They are dis-
solved in organic solvent or dispersed in aqueous mediumeg highly substituted cellulose making them water-insoluble example Ethyl Cellulose (EC)Enteric Coating Polymers
(a) Methacrylic Acid The presence of carboxylic acidgroups renders this class to be insoluble in water at low pH
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Gaur et al Film Coating Technology Past Present and Future
Table I Film coatings are available based on the following polymeric materials
pH Independent polymer for rapidly disintegrating film coating
1 Neutral co-polymer Film coat E30D For film coating of tabletspellets granules powders
Natural polymer
1 Xanthan gum Film coating of tablets2 Pectin Film coating of tablets3 Chitosan Film coating of tablets4 Okra gum Film coating of tablets5 Grewia gum Film coating of tablets
(stomach) but as the pH rises towards neutrality in upperpart of the small intestine the coating gradually dissolvesExample Eudragit(b) Phthalate esters These polymers contain free car-boxylic acid making them acid insoluble however in intes-tine they become deprotonated and dissolves in basicmedia They are also called enteric coating polymers egCellulose acetate phthalate (CAP) Enteric coating poly-mers can be classified into 3 groups based on chemicalcompositions as listed below
The solubility of the polymers depend on the numberof carboxylic acid groups Enteric formulations shouldhave less than 10 drug release in 2 hours during acidstage The completion of the drug release in the continu-ation testing in the buffer stage should take place within45 min Classification of Polymers Based on Derivatives(Lehmann 1994 Libermen and Lachman 2003 Malm
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Film Coating Technology Past Present and Future Gaur et al
and Waring 1937 Sadeghi et al 2001 Ogaji and Nnoli2010 Ogaji and Hoag 2011 Ogaji et al 2013)
PlasticizersPlasticizers are relatively low molecular weight materialswhich are used as additives in pharmaceutical coating for-mulations to reduce the brittleness and increase the flex-ibility of the resulting film They act by weakening intermolecular attraction between polymer chains and facili-tating coalescence of discrete polymer spheres of aque-ous dispersed systems during film formation Adhesive andmechanical properties of the coating and subsequent drugrelease are dependent on the concentration of plasticizersto a great extent Plasticizers are non volatile componentsand therefore are responsible for the weight gain of dosageforms during coating A plasticizer has to be miscible andfulfil all the compatibility parameters with the polymerbeing usedAn important consideration is the content of plasticizer
as it can affect the glass transition temperature (Tg) soit should be experimentally determined by evaluating thechanges in Tg of polymer as the plasticizer content isincreased Tg is the temperature for amorphous polymersat which the behaviour of the film changes from hard andbrittle to soft and elastic An effective plasticizing agentis one which exhibits a greater decrease in the Tg of thefilm Changes in the mechanical properties of the poly-meric film are an indication of plasticizer efficacy (Seitzet al 1988 Wu and McGinity 2001)Plasticizers are classified into three groups
Anti-AdherentsAnti-adherents are used as additives to avoid agglomera-tion of the substrates during both the coating process andon subsequent storage One of the most common anti-adherents used in pharmaceutical coatings is talc but sinceit has to be used at high concentration it creates pro-cessing challenges including clogging of the spray noz-zle during coating and particle sedimentation It tends todecrease water vapour permeability and also the dissolu-tion rate of drugs due to its hydrophobic nature It alsoaffects the mechanical and adhesive properties of polymerfilms so now Glyceryl monostearate has been found as analternative to talc
Opacifying AgentsColorantsPigments deliver elegance and stability enhancement tothe solid dosage form Water-insoluble lakes and the iron
oxides are most commonly used pigments Colour migra-tion and stability issues have diminished the use of thewater-soluble dyes in film coating Pigments can signifi-cantly affect the mechanical and permeability properties ofthe film An inverse relation-ship between film-tablet adhe-sion and the particle size of the pigment has been reportedStudies have shown that the shape of the pigment par-ticle and the extent of polymer-particle interaction influ-ence the elastic modulus of polymeric films and surfacepolarity of pigments influences drug release In additionchemical incompatibilities between the pigment and thepolymer have also been reported predominantly relatedto the size and surface charge of the components andthe pH of the medium One important concept relevantto pigments is the critical pigment volume concentration(CPVC) this is the maximum concentration (based on vol-ume) of the insoluble material that can be incorporated intoa film without compromising film properties If the CPVCis exceeded insufficient polymer is present to surroundall the insoluble particles resulting in marked changes indifferent properties of the film Colorants are mainly clas-sified in to three types(i) Organic dyes and their lakes eg Erythrosine tar-trazine Sunset yellow(ii) Inorganic colours eg Iron oxide yellow red andblack titanium dioxide talc(iii) Natural colours eg Riboflavin Anthocyanins andCarmine
SolventsVehiclesThe key function of a solvent system is to dissolve ordisperse the polymers and other additivesThe major classes of solvents being used are aqueous
(Water) and Nonaqueous (Alcohols Ketones Esters Chlo-rinated hydrocarbons) Because of environmental and eco-nomic concerns water is the most commonly used solvent
Miscellaneous Coating Solution ComponentsSolid dosage form may be incorporated with several spe-cial materials such asFlavours and sweeteners are added to mask unpleasant
odours or to develop the taste eg fruit spirits (organicsolvent) aspartame water soluble pineapple flavourSurfactants are ancillary to stabilize immiscible or insol-
uble ingredients in the coating They facilitate substratewettability and promote coalescence of polymeric materialover the substratersquos surface eg Spans Tweens etcAntioxidants are incorporated to stabilize a dye system
to oxidation and colour change eg oximes phenols etcAntimicrobials are added to inhibit microbial growth
in the coating composition Various cellulosic materialsare mainly prone to microbial growth and they can notbe stored in solution form eg Carbamates alkylisothia-zloinone benzothiazoles etc
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Gaur et al Film Coating Technology Past Present and Future
CURRENT TRENDS IN FILM COATING ANDFUTURE DIRECTIONSOpadry formulations provided numerous advantages ver-sus the use of individual raw materials including thereduction of the number of raw materials for Qualitycontrol testing reduced preparation time reliable colour-matched formulations tremendous appearance and excel-lent mechanical parameters However opadry dispersionsolids must be stored as 10ndash15 ww aqueous solution toattain workable 300ndash600 centipoises viscosityOpadry II category consisting HPMC and polysaccha-
rides was introduced to increase productivity The mostsignificant recent advances in the development of fully for-mulated aqueous film coatings have been the introductionof new film coatings based on polyvinyl alcohol (PVA)and sodium carboxymethylcellulose (NaCMC) PVA-basedfilms are known to have relatively low permeability formoisture vapour and oxygen whereas NaCMC-based coat-ings are glossy and have low oxygen permeability andrelatively high permeability for water vapourOpadry aqueous moisture barrier (AMB) and Opadry II
85 series are two proprietary families of PVA-based prod-ucts that were commercialized in the mid to-late 1990sThe Opadry AMB formulation were optimized to providethe lowest moisture vapour transmission rate Opadry II85 products give moisture vapour transmission rate almostas low as Opadry AMB but can be applied at significantlyhigher spray ratesFilm coatings based on PVA and NaCMC offer various
advantages Now moisture-sensitive drugs can be coatedin an aqueous coating process by PVA-based coatingsNaCMC based coatings provide demonstrable oxygenbarrier properties and excellent aesthetic characteristics(Porter and Felton 2010)
Supercelltrade Coating TechnologyThe ldquostandardrdquo practice of tablet coating often delivers anon-homogenous product Because the tablets are loadedin large rotating pans and vented for hot air drying edgesof tablets can get grounded off and intagliation can getfilled in by coating material leading to uneven coating onedgescorners and tablet faces This inaccuracy limits theuse of modified release coatings In a laboratory it is nec-essary to coat several kilograms of tablets at one timemaking RampD of a tablet dosage form costly and difficultFurther extremely hygroscopic as well as flat or other
oddly shaped tablets cannot be coated using present tech-nology so SCT (Niro Pharma Systems) technology uses asmall modular design that accurately deposits controlledamounts of coating materials on friable and extremelyhygroscopic tablets SCTrsquos continuous small-batch capablecoating process is predictable and efficient In SCT thetablets are coated in batches ranging from 30 to 120 gramswhich linearly scale up to production capacity In this tech-nique the tablets are covered with the polymer spray in
the same direction as the hot air resulting in an efficientprocess Due to SCTrsquos unique air distribution plate designthe tablets move very quickly and predictably through thespray zone receiving only a small amount of coating perpass and therefore achieving higher coating accuracy Theprocess time is short in seconds or in minutes as opposedto hours and therefore gentler on the tablets (Systems2012)Supercelltrade Coating Technology may also be used for
coating of flat or highly oblong tablets or friable tabletsIn this process drying is very fast making it possible tocoat extremely hygroscopic tablets The deposition accu-racy is sufficiently high to layer API onto tablets and uni-form layers of taste masking or modified release coatingscan be applied consecutively within a single continuousbatchUnique features of super cell coating technology are
(1) Continuous coating(2) Short processing time(3) Flexible modular design(4) No scale-up to parameters(5) Batch size for RampD (Minimum size sim30 grams)(6) Enhancing technology(7) Multi-layer coating(8) Low humidity process suitable for moisture sensitivematerials
Syloidreg FP Silicas inPharmaceutical Film CoatingsRecently film coatings have also shown encouragingresults to enable the oral delivery of peptide therapeuticsSyloidreg FP silicas have been used as excipients in manypharmaceutical formulations due to their unique morphol-ogy The combined adsorption capacity porosity particlesize and greater surface area allow them to provide severalbenefits simultaneously which can expedite manufacturingand improve efficacy of the final dosage form Syloidreg FPsilica can be used in polymeric coating systems in combi-nation of vinylcellulose or acrylic polymers (13 Septem-ber 2010)In standard concentrationsmdashAddition of Syloidreg 244FP
silica to film coating provides following advantages-Improved spray propertiesElimination of the need for talcImprovement of suspension propertiesPrevention of valve cloggingMinimal settling in spray linesSmoothen tablet surfaceReduction of adhesionApplications Anti-tacking agent Oral peptide deliveryODT formulations Enteric coatings Sustained releasecoatings Controlled release coatings (Grace Discovery)In recent years there has been a growing focus on
conducting fundamental studies through the applicationof appropriate modelling techniques and novel analytical
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Film Coating Technology Past Present and Future Gaur et al
technologies In addition recent trends are directed towardimprovements in processing as well as development ofnovel release functionality The following section providesa review to some of these areas
PROCESS MODELLING SYSTEMS ANDTHEIR APPLICATIONSFilm coating process comprises various steps which canbe direct or indirect Direct parameters include air pres-sure and flow temperature of coating spray and tabletcore and spray rate The indirect parameters take accountof droplet size distribution and viscosity coating unifor-mity and thickness So different modelling systems havebeen proposed eg Digital video imaging Discrete ele-ment methodologies (DEM) Computational fluid dynam-ics (CFD)Discrete element method embodies different techniques
implying on a large number of small particles to figure outthe movement and their interaction In film coating pro-cedure DEM is used for estimating movement of tabletsand predicting the coating uniformity Computational fluiddynamics applies the principles of fluid mechanics for filmcoating process (Felton and Porter 2013 Felton 2007)The major application of process analytical technique is
that it is amenable to automation So it can be applied formonitoring and controlling various unit operations It canbe applied for product moisture content amount of coatingapplied endpoint of the process and properties of coatingeg porosity and densityHowever adaptation of PAT for coating process requires
positioning of sensors in unsuitable conditions whichcan have a bearing on sensor sensitivity So varioussophisticated analytical processes eg terahertz refractiveindex (TRI) and pulse imaging (TPI) near-infrared andraman spectroscopy (NIR) laser-induced breakdown spec-troscopy (LIBS) and confocal laser techniques can beapplied offline All of these techniques can also be usedonline since these are non-destructive except LIBSNIR methods can be employed for determining the coat-
ing amount to predict drug release rate in combinationwith multivariate analysis NIR spectroscopy can be usedto estimate an API in a coated tablet with plusmn 4 targetvalue in comparison to HPLC Major advantage of NIRspectroscopy is its non-invasiveness and rapidity Howeverit cannot be used with drugs in hydrate form Raman spec-troscopy is less sensitive to hydrates TPI technique can beused to determine the amount of coating in a side-ventedpan (Felton 2007 Felton and Porter 2013)
CONCLUSIONBased on the facts regarding film coating process we canemphasize that various recent trends may drive the indus-try closer to large scale adoption of dry powder coatingtechnologies for oral delivery First the current changes
in global austerity have pushed many pharmaceutical andbiotechnology companies to seriously examine manufac-turing costs The lower cost associated with dry powdercoating technology makes it attractive for both brand andgeneric companies seeking to reduce operating expensesAnother major driver in the future will be the needs of
advanced drug products specifically focused in the area ofcounterfeit resistance and amorphous formulation supportCounterfeit drugs are a major problem facing global phar-maceutical companies with steps being taken to protectthe supply chain and also develop visually differentiatedproducts Dry powder coating particularly electrostatic drypowder coating can be used to prepare novel identificationmarks onto drug products in a rapid cost effective mannerleading to enhanced brand identificationBeyond this the potential to eliminate the need for sol-
vents allows for more effective application of coatings tomoisture sensitive products This opens up unique oppor-tunities in the drug product design of amorphous systemsand may potentially play a role in future product designsGiven the potential of the technology academic researchwill continue in earnest as the pharmaceutical industrycontinues the adoption of the technology Over time anddriven by a number of different factors dry powder coatingappears poised to become a major pharmaceutical coatingtechnology in the future
Acknowledgment The authors wish to express thegratitude towards administrative authorities at ITSParamedical (Pharmacy) College Muradnagar Ghaziabadfor providing necessary support during collection of data
REFERENCESAulton M (ed) (1995) Mechanical properties of film coats Tay-lorampFrancis London
Bodmeier R and Paeratakul O (1994) Mechanical properties of dry andwet cellulosic and acrylic films prepared from aqueous colloidal polymerdispersions used in the coating of solid dosage forms PharmaceuticalResearch 11 882ndash88
Chen W Chang S-Y Kiang S Early W Paruchuri S and DesaiD (2008) The measurement of spray quality for pan coating processJ Pharm Innov 3 3ndash14
Chen W Chang S Y Kiang S Marchut A Lynberg O Wang JRao V Desai D Stamato H and Early W (2010) Modeling of pancoating process Prediction of tablet content uniformity and determinationof critical process parameters J Pharm Sci 99 3213ndash24
Cole G (1998) Pharmaceutical Coating Technology Taylor and FrancisLondon
Dillon R E Matheson L A and Bradford E B (1951) Sintering ofsynthetic latex particles Journal of Colloid Science 6 108ndash17
Felton L A (2007) Characterization of coating systems AAPS PharmSci Tech 8 112
Felton L A and Porter S C (2013) An update on pharmaceutical filmcoating for drug delivery Expert Opinion on Drug Delivery 10 421ndash35
Franz R and Doonan G (1983) Measuring the surface temperature oftablet beds using infrared thermometry Pharm Technol 7 55ndash67
66 J Pharm Sci Pharmacol 1 57ndash67 2014
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Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
Harris M R and Sellassie G (eds) (1997) Aqueous Polymeric Coat-ing for Modified Release Oral Dosage forms Marcel Dekker Inc NeyYork
Hogan J (1998) Pharmaceutical Coating Technology Taylor and FrancisLtd London
Lachman L Lieberman H A and Joseph L K (1989) The Theoryand Practice of Industrial Pharmacy vol 3 Varghese Publishing HouseMumbai
Lehmann K (ed) (1994) Coating of multiparticulates using polymericsolutions Formulation and process considerations Marcel Dekker IncNew York
Libermen H and Lachman L (2003) Pharmaceutical Dosage FormsTablets Marcel Dekker Inc NY Vols 1ndash3
Lipper R D Desai D and Kiang S (September 11ndash12 2006) CaseStudy Implementation of Design Space Concepts in Development of anActive-Coated Tablet In Real World Applications of PAT and QbD inDrug Process Development and Approval Bristol-Myers Squibb Pharma-ceutical Research Institute Arlington Virginia USA
Lippold B C and Monells P P (2001) Film formation reproducibilityof production and curing with respect to release stability of functionalcoatings from aqueous polymer dispersions Pharmazie 56 5ndash17
Malm C J and Waring C E (1937) Cellulose esters containing dicar-boxylic acid groups and process of making the same
Mazer T B Meyer G A Hwang S M Candler E L Drayer LR and Daab-Krzykowski A (1992) System for delivering an activesubstance for sustained release
Narang A K M Castoro J Varia S and Desai D (2011) Effect ofPro- and Anti-Oxidants on the Formation of Formyl Species in PVA- andPEG-Based Tablet Coating Material AAPS Washington D C USA
Narang A S Desai D and Badawy S (2012) Impact of excipientinteractions on solid dosage form stability Pharm Res 29 2660ndash83
Ogaji I and Nnoli O (2010) Film coating potential of okra gum usingparacetamol tablets as a model drug Asian J Pharm 4 130ndash34
Ogaji I J and Hoag S W (2011) Effect of grewia gum as a suspend-ing agent on ibuprofen pediatric formulation AAPS PharmSciTech 12507ndash13
Ogaji I J Okafor I S and Hoag S W (2013) Grewia gum as a poten-tial aqueous film coating agent I Some physicochemical characteristicsof fractions of grewia gum J Pharm Bioall Sci 5 53ndash60
Okutgen E Jordan M Hogan J E and Aulton M E (1991) Effectsof tablet core dimensional instability on the generation of internal stresses
within film coats part II Temperature and relative humidity variationwithin a tablet bed during aqueous film coating in an accela-cota DrugDevelopment and Industrial Pharmacy 17 1191ndash99
Opadryreg Complete Film Coating System Coating ParametersndashAqueous Formulas Colorcon Inc North America BPSI HoldingsLLC
Porter C (1990) Coating of Pharmaceutical Solid Dosage Forms MackPublishing Company Easton Pennsylvania
Porter S C (ed) (2011) Scale-Up of Film Coating Informa HealthcareNew York
Porter S C and Felton L A (2010) Techniques to assess film coat-ings and evaluate film-coated products Drug Development and IndustrialPharmacy 36 128ndash42
Rekhi G S Porter S C and Jambhekar S S (1995) Factors affectingthe release of propranolol hydrochloride from beads coated with aque-ous polymeric dispresions Drug Development and Industrial Pharmacy21 709ndash29
Sadeghi F Ford J L Rubinstein M and Rajabi-Siahboomi A R(2001) Study of drug release from pellets coated with surelease con-taining hydroxypropyl methylcellulose Drug Development and IndustrialPharmacy 27 419ndash30
Savage G V and Rhodes C T (1995) The sustained release coating ofsolid dosage forms A historical review Drug Development and Indus-trial Pharmacy 21 93ndash118
Seitz J A Swarbrick J and Boylan J C (1988) Aqueous film coat-ing Encyclopedia of Pharmaceutical Technology Marcel Dekker NewYork pp 337ndash49
Singh P Solanky T K Mudryya R Pfefferc R and Davea R (2001)Estimation of coating time in the magnetically assisted impaction coatingprocess Powder Technology 121 159ndash67
Syloidreg FP silica excipientsmdashmore than just Silica (Belgium Fred Mon-suur Grace Davison Discovery Sciences) (13 September 2010)
Systems GNP (2012) SUPERCELLtrade Tablet Coating Technology (SCT)Niro Inc 9165 Rumsey Road Columbia MD 21045 USA
Wu C and McGinity J W (2001) Influence of Ibuprofen as a solid-state plasticizer in Eudragit RS 30D on the physicochemical propertiesof coated beads AAPS PharmSciTech 2 1ndash9
Zheng W and McGinity J W (2003) Influence of Eudragit NE 30 Dblended with Eudragit L 30 D-55 on the release of phenylpropanolaminehydrochloride from coated pellets Drug Development and IndustrialPharmacy 29 357ndash66
J Pharm Sci Pharmacol 1 57ndash67 2014 67
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Film Coating Technology Past Present and Future Gaur et al
molecular weight and particle size coating liquid con-stituents and properties like viscosity and surface Sincecoalescence occurs above a minimum film formation tem-perature (MFT) temperature and rate of water evaporationare major process-related factors affecting the properties ofcoatings Usually a thermal after-treatment (curing) is doneto remove the film defects (Aulton 1995 Lachman et al1989)
Process ParametersThe spraying rate affects the moisture content which inturn affects quality and uniformity of the film A low sprayrate will give a brittle film due to incomplete coalescencedue to inadequate wetting and a high spray rate causesover wetting resulting in picking and sticking The sprayrate also interacts with tablet temperature and a low tablettemperature with high spray rate can produce cracks inthe film Increase in pressure reduces the surface rough-ness by producing thin dense film however excessive pres-sure forms very fine droplets which spray dries beforegetting to tablet bed causing spray loss The inlet air tem-perature impacts the drying process and coating unifor-mity High temperature enhances the drying efficiency anddecreases the water penetration however too much air tem-perature can cause premature drying and reduces the effi-ciency Since water is less volatile than organic solventsand requires higher drying capacity resulting in higherenergy cost of the entire coating process Ideal Cures PvtLtd has developed some products (INSTACOAT rangefor example Instacoat EHP 250 Instacoat EMB InstacoatEEN Instacoat EHA Instacoat Aqua Instacoat Aqua IIInstacoat Aqua III and Instacoat P4) which dries faster andthe whole coating process can be completed in the sameor sometimes little less time as compared to organic sol-vent based coatings The increase in rotating speed canimprove the mixing but to a certain level An increase inthe pan speed reduces variation in thickness and enhancesthe coating uniformity however a excessively high speedcan lead to undesired breakage
Air Pressure of AtomisationUsually the drug should be stable to withstand all the pro-cessing parameters as per the specification however it isimportant to consider the properties of the drug There is astrong potential of interaction that can occur between thedrug and polymeric material or any other additive Poly-meric material after atomisation can possibly dissolve theouter layer of the substrate and the components of the lat-ter may also migrate eg migration and subsequent recrys-tallization of propranolol HCl in Eudragit NE 30D filmsso sub-coating is done to overcome this problem as it pre-vents interactions and it is suitable when enteric coatingis being done on an acid-labile drug as enteric coatingpolymers are acidic in nature (Rekhi et al 1995)Size and shape of the substrate is also of consider-
able importance as its movement within the equipment is
deeply influenced A biconvex round tablet is preferred asflat tablets tend to agglomerate during the process Thereare possibilities of shallow convex tablets undergoing abra-sion due to its sharp edges and thus sub-coating becomesessentialSurface wettability is important as wetting and spread-
ing of the polymer material is related to the smoothness ofthe film and adhesion to the substrate Coated multipartic-ulate systems offer several advantages over larger singleunit dosage forms especially when applied to modified-release coatings due to greater uniformity in GI transittime and a reduced potential for premature release Thesecoated particles can be filled into capsules or compressedinto tablets When compressing coated particles the forceused during the tabletting process and the mechanicalstrength of the coating are critical Faster drug release mayoccur if the film cracks or fractures during compactionwhile slower drug release has been reported when the coat-ings fuse together to form a matrix Excipients such asmicrocrystalline cellulose minimize direct contact of thecoated pellets and dissipate the compression forces to pre-vent film fracturePolymeric films adhere to the substrate surface using
two major forces namely the strength of the interfa-cial bonds and the internal stresses within the film Theprimary type of interfacial bonding is hydrogen bond for-mation although dipole and dipole-induced dipole interac-tions also occur Substrate considerations such as surfaceroughness tablet hardness and substrate hydrophobicitycan affect the strength of interfacial bonding In contrastinternal stresses which arise from forces due to shrinkageof the film upon solvent evaporation thermal stress due tothe differences in thermal expansion of the film and thesubstrate and volumetric stress due to swelling during stor-age tend to weaken adhesion Use of excipients with ther-mal expansion coefficients similar to that of the polymercan reduce internal stresses and improve polymer adhesion(Lippold and Monells 2001 Okutgen et al 1991 Franzand Doonan 1983)
Dry CoatingThere are several disadvantages of using the solventswhether aqueous or organic eg drying time and microbi-ological stability for aqueous coating whereas safety andenvironment hazards for organic solvents These issueshave led to the adoption of dry powder coating techniquesin a number of other industries Among these are technolo-gies which range from the atomization of molten materialscommonly known as melt coating to softened powder lay-ering and electrostatic adhesion Types of Dry Coating areas follows (Felton and Porter 2013)
Electrostatic Dry CoatingThis novel coating technique is an alternative to aqueousor solvent based coating process is widely useful in foodtechnology paint technology metal coatings coating of
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Gaur et al Film Coating Technology Past Present and Future
living cells and coating of tablets as well as capsules Theprinciple of electrostatic powder coating states that spray-ing of a mixture of finely grounded particles and polymersonto a substrate surface without using any solvent and thenheating the substrate for curing in oven until the powdermixture is fused into filmAccording to the charging mechanism there are two
types of spraying units namely(a) Corona charging(b) Tribo charging
Magnetically Assisted Impaction CoatingIn this technique the particles are assumed to stay in afluidized state where the distribution of velocities is aMaxwellndashBoltzmann type It is assumed that the collisionsoccurring among the particles are important for impingingthe guest particles onto the surface of host particles therebymaking a transient surface on the host particles The coatingtime depends on various parameters eg properties of thehost and guest particles number of host particles height ofthe fluidized bed and ratio of the host and guest particlesdiameters For a particular coating time the bed height andparticle size should be optimum (Singh et al 2001)
Film Formation Mechanisms inDry Powder CoatingFilm formation takes place by a process of evaporationcoalescence and sintering which are influenced by pro-cess and formulation considerations During the dry pow-der coating process the substrates are often heated abovethe glass transition temperature of the layering materialsso that the coating materials soften and adhere to the sub-strate For conventional film coating spreading and adher-ence is not limited by mobility however powder systemsmay become limited by mobility particularly when liquidlevels are reduced to the point where solid particle defor-mation becomes rate limiting This introduces a series ofconstraints related to mechanical and thermal propertiesof the coating formulation Coalescence and film forma-tion are therefore dependent on these properties as wellAs such glass transition temperature and plastic deforma-tion characteristics of the coating materials are paramountto the success of the process Many pharmaceutical coat-ing materials are amorphous polymers exhibiting a glasstransition temperature related to the change from a glassto a super cooled liquid On transition which occurs at aspecific temperature mobility of the system increases sig-nificantly The greater mobility allows for molecular rear-rangement and alters the plastic deformation characteristicsof the materialsThe mechanism of film formation of the powders lay-
ered onto the solid cores ismdashsummarized as (Felton andPorter 2013 Felton 2007)(i) Coalescence and sintering of the particles of the poly-meric materials in a process that involves the partial fusionof the polymer
(ii) Levelling of the coating material includes densifica-tion of the layer with reduction of the empty spaces andsmoothening of the surface(iii) Cooling of the layer and hardening of the coating
Based on FunctionProtective CoatingsThin films of water soluble polymers are often appliedfor taste or odour masking or to improve the stabilityof moisture sensitive products or for better mechanicalresistance of the product during handling Such protectivecoatings need to remain intact for the short time of swal-lowing and after that they should immediately dissolve toensure immediate drug release These polymers are water-soluble eg cellulose ethers (eg hydroxypropyl methyl-cellulose (HPMC)) polyvinyl acetate (PVA) or polyvinylpyrrolidone (PVP) Eudragitreg E is a methacrylic copoly-mer insoluble in saliva but rapidly dissolves in the acidicpH of the stomach Sometimes enteric polymers eg shel-lac can also be applied at very low concentration whichgives very low film thickness insufficient to provide gastricresistance and disintegrates in the stomach within 30 min(Lehmann 1994 Porter 1990 Porter 2011)
Functional CoatingsFilm coatings which are applied to achieve a desiredrelease profile are usually termed modified-release orfunctional coatings Those intended to protect the drugfrom the acidic environment of the stomach are entericcoatings Extended release coatings in contrast areintended to control the release of the drug over a prolongedperiod of time (Porter 1990)Enteric Coatings Enteric coatings are prepared from
gastric resistant polymers which remain intact in stom-ach but immediately dissolve in small intestine Themost effective enteric polymers contain many carboxylicgroups with a pKa of 3ndash5 Therefore they will dissoci-ate and dissolve only when the pH rises above this value(Porter 2011 Lehmann 1994) Before the synthetic poly-mers were introduced to the market shellac a naturalpolymer was one of the main polymer used for this pur-pose Cellulose acetate phthalate (CAP) was the first syn-thetic polymer described in 1937 which soon gained highpopularity as a gastric resistant polymer Later polyvinylacetate phthalate (PVAP) and hydroxypropyl methylcel-lulose phthalate (HPMCP) were preferred due to theirlower permeability in the gastric fluid and improved sta-bility against hydrolysis Today methacrylate copolymersEudragitreg L and S are two of the most widely used poly-mers for this purpose (Malm and Waring 1937 Zheng andMcGinity 2003)Extended Release Coatings The patient compliance is
usually inversely proportional with the frequency of drugadministration especially when multiple daily administra-tions are necessary to maintain constant blood levels of the
J Pharm Sci Pharmacol 1 57ndash67 2014 61
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Film Coating Technology Past Present and Future Gaur et al
drug Therefore extended release polymers were devel-oped which are able to provide a sustained action by acontrolled release over time Waxes and some natural poly-mers were already discovered earlier to be useful to pro-long the drug release if coated onto the solid dosage formsMostly their mechanism of performance is based on slowdegradation or erosion Polymers for extended release arein general insoluble in water over the entire pH range Thedrug release is thus controlled by diffusion through thehydrated polymer or through cracks or water-filled poresThere are still only few polymers available on the mar-ket for extended release eg cellulose acetate ethylcel-lulose or the methacrylic acid copolymers Eudragitreg RSRL and NE Combinations of ethylcellulose with waxeswater-soluble or enteric polymers were investigated toachieve extended drug release for drug with varying oreven pH-dependent solubilities Synthetic polymers how-ever do not fit into the overall product concept of phyto-pharmaceutical products or as for nutraceuticals they arenot approved Therefore several attempts were undertakento achieve sustained drug release by using only naturalpolymers The drug release from silk fibroin coated tabletsafter cross-linking with a carbodiimide was extended toseveral hours (Savage and Rhodes 1995) Shellac is alsoable to provide prolonged drug release at higher coatinglevels or as matrix forming material However there is nodrug release for such systems in the gastric medium due tothe enteric property of shellac Zein as a water-insolublenatural polymer is an alternative for extended drug releaseespecially in combination with an additional enteric top-coat (Mazer et al 1992)
Active CoatingIn it the drug is embedded into the coat to formulate afixed dose combination or to modify the release profileThe beadlets are then filled into capsules however the vol-ume limitation of capsules makes it an unsuitable approachfor higher dose drugs (Seitz et al 1988)This is particularly useful for the drugs unstable at
high mechanical stress In an active coating process com-mon pharmaceutical operations can be avoided Drugs thatundergo acid or base catalysed degradation have been sta-bilized by this technique It gives relatively high drug toexcipient ratio than encapsulating such molecules in thetablet core Fixed dose combinations can be formulated bythis approach (Hogan 1998)The primary concerns of an active coating process
are end-point content uniformity efficiency and stabilitywhich are either directly or indirectly affected by pro-cess parameters such as rate of spraying inlet air temper-ature residual moisture pan speed atomisation pressureand drug properties The end point is estimated by the gainin tablet weight or quantity of coating suspension sprayedPeriodically tablets are sampled and analysed for the drugamount (Lipper et al September 11ndash12 2006) Severalmathematical models have been proposed to ascertain a
correlation between coating parameters and content unifor-mity but the model proposed by Cheng et al has confirmedto be most robust (Chen et al 2010 Chen et al 2008)Coating time is also an important parameter since a
longer coating time results in better content uniformity butit makes the process not amenable for a high volume prod-uct On the other hand too short coating time can lead toincomplete coating process Spray zone width should notbe too narrow or too wide If the tablet bed has not beenappropriately covered then there will be either unsprayedsubstrate or unused deposit of coating solutionCoating process should yield the tablets having required
polymorphic forms and the coating suspension shouldcrystallise after drying The stability is adversely affectedif the coating stays in amorphous state The polymor-phism also depends on coating excipients eg plasticisers(Narang et al 2011 Narang et al 2012 Chen et al 2010Chen et al 2008)Effectiveness of the Active Coating Process The coat-
ing efficiency improves significantly when the droplet sizeis smaller than 10 m By appropriate selection of atomiz-ing and pattern air volume the fraction of droplets smallerthan 10 microns can be reduced to improve the overallefficiency of the coating process Factors governing themsuch as high ratios of the suspension spray rate to atom-ization air flow rate suspension spray rate to pattern airflow rate or atomization air flow rate to pattern air flowrate can improve the coating efficiency
FILM COATING FORMULATIONCOMPONENTSPolymersA polymer is a large molecules made up of many identicalsubunits of monomers (Table I)
Immediate Release Coating PolymersCellulose Derivates The most widely used cellulosic
polymers is Hydroxypropyl Methyl Cellulose (HPMC)which is readily soluble in aqueous medium and forms flex-ible strong films which adhere to the core Other examplesMC (Methyl Cellulose) and HPC (Hydroxypropyl Cellu-lose) (Hogan 1998 Lachman et al 1989 Lehmann 1994)Vinyl Derivates The most widely used vinyl polymer
is Poly Vinyl Pyrrolidone (PVP) however it has inherenttackiness For better film coating its copolymer with vinylacetate is used
Modified Release Coating PolymersExtended Release Coating Polymers They are dis-
solved in organic solvent or dispersed in aqueous mediumeg highly substituted cellulose making them water-insoluble example Ethyl Cellulose (EC)Enteric Coating Polymers
(a) Methacrylic Acid The presence of carboxylic acidgroups renders this class to be insoluble in water at low pH
62 J Pharm Sci Pharmacol 1 57ndash67 2014
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Gaur et al Film Coating Technology Past Present and Future
Table I Film coatings are available based on the following polymeric materials
pH Independent polymer for rapidly disintegrating film coating
1 Neutral co-polymer Film coat E30D For film coating of tabletspellets granules powders
Natural polymer
1 Xanthan gum Film coating of tablets2 Pectin Film coating of tablets3 Chitosan Film coating of tablets4 Okra gum Film coating of tablets5 Grewia gum Film coating of tablets
(stomach) but as the pH rises towards neutrality in upperpart of the small intestine the coating gradually dissolvesExample Eudragit(b) Phthalate esters These polymers contain free car-boxylic acid making them acid insoluble however in intes-tine they become deprotonated and dissolves in basicmedia They are also called enteric coating polymers egCellulose acetate phthalate (CAP) Enteric coating poly-mers can be classified into 3 groups based on chemicalcompositions as listed below
The solubility of the polymers depend on the numberof carboxylic acid groups Enteric formulations shouldhave less than 10 drug release in 2 hours during acidstage The completion of the drug release in the continu-ation testing in the buffer stage should take place within45 min Classification of Polymers Based on Derivatives(Lehmann 1994 Libermen and Lachman 2003 Malm
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Copyright American Scientific Publishers
Film Coating Technology Past Present and Future Gaur et al
and Waring 1937 Sadeghi et al 2001 Ogaji and Nnoli2010 Ogaji and Hoag 2011 Ogaji et al 2013)
PlasticizersPlasticizers are relatively low molecular weight materialswhich are used as additives in pharmaceutical coating for-mulations to reduce the brittleness and increase the flex-ibility of the resulting film They act by weakening intermolecular attraction between polymer chains and facili-tating coalescence of discrete polymer spheres of aque-ous dispersed systems during film formation Adhesive andmechanical properties of the coating and subsequent drugrelease are dependent on the concentration of plasticizersto a great extent Plasticizers are non volatile componentsand therefore are responsible for the weight gain of dosageforms during coating A plasticizer has to be miscible andfulfil all the compatibility parameters with the polymerbeing usedAn important consideration is the content of plasticizer
as it can affect the glass transition temperature (Tg) soit should be experimentally determined by evaluating thechanges in Tg of polymer as the plasticizer content isincreased Tg is the temperature for amorphous polymersat which the behaviour of the film changes from hard andbrittle to soft and elastic An effective plasticizing agentis one which exhibits a greater decrease in the Tg of thefilm Changes in the mechanical properties of the poly-meric film are an indication of plasticizer efficacy (Seitzet al 1988 Wu and McGinity 2001)Plasticizers are classified into three groups
Anti-AdherentsAnti-adherents are used as additives to avoid agglomera-tion of the substrates during both the coating process andon subsequent storage One of the most common anti-adherents used in pharmaceutical coatings is talc but sinceit has to be used at high concentration it creates pro-cessing challenges including clogging of the spray noz-zle during coating and particle sedimentation It tends todecrease water vapour permeability and also the dissolu-tion rate of drugs due to its hydrophobic nature It alsoaffects the mechanical and adhesive properties of polymerfilms so now Glyceryl monostearate has been found as analternative to talc
Opacifying AgentsColorantsPigments deliver elegance and stability enhancement tothe solid dosage form Water-insoluble lakes and the iron
oxides are most commonly used pigments Colour migra-tion and stability issues have diminished the use of thewater-soluble dyes in film coating Pigments can signifi-cantly affect the mechanical and permeability properties ofthe film An inverse relation-ship between film-tablet adhe-sion and the particle size of the pigment has been reportedStudies have shown that the shape of the pigment par-ticle and the extent of polymer-particle interaction influ-ence the elastic modulus of polymeric films and surfacepolarity of pigments influences drug release In additionchemical incompatibilities between the pigment and thepolymer have also been reported predominantly relatedto the size and surface charge of the components andthe pH of the medium One important concept relevantto pigments is the critical pigment volume concentration(CPVC) this is the maximum concentration (based on vol-ume) of the insoluble material that can be incorporated intoa film without compromising film properties If the CPVCis exceeded insufficient polymer is present to surroundall the insoluble particles resulting in marked changes indifferent properties of the film Colorants are mainly clas-sified in to three types(i) Organic dyes and their lakes eg Erythrosine tar-trazine Sunset yellow(ii) Inorganic colours eg Iron oxide yellow red andblack titanium dioxide talc(iii) Natural colours eg Riboflavin Anthocyanins andCarmine
SolventsVehiclesThe key function of a solvent system is to dissolve ordisperse the polymers and other additivesThe major classes of solvents being used are aqueous
(Water) and Nonaqueous (Alcohols Ketones Esters Chlo-rinated hydrocarbons) Because of environmental and eco-nomic concerns water is the most commonly used solvent
Miscellaneous Coating Solution ComponentsSolid dosage form may be incorporated with several spe-cial materials such asFlavours and sweeteners are added to mask unpleasant
odours or to develop the taste eg fruit spirits (organicsolvent) aspartame water soluble pineapple flavourSurfactants are ancillary to stabilize immiscible or insol-
uble ingredients in the coating They facilitate substratewettability and promote coalescence of polymeric materialover the substratersquos surface eg Spans Tweens etcAntioxidants are incorporated to stabilize a dye system
to oxidation and colour change eg oximes phenols etcAntimicrobials are added to inhibit microbial growth
in the coating composition Various cellulosic materialsare mainly prone to microbial growth and they can notbe stored in solution form eg Carbamates alkylisothia-zloinone benzothiazoles etc
64 J Pharm Sci Pharmacol 1 57ndash67 2014
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Gaur et al Film Coating Technology Past Present and Future
CURRENT TRENDS IN FILM COATING ANDFUTURE DIRECTIONSOpadry formulations provided numerous advantages ver-sus the use of individual raw materials including thereduction of the number of raw materials for Qualitycontrol testing reduced preparation time reliable colour-matched formulations tremendous appearance and excel-lent mechanical parameters However opadry dispersionsolids must be stored as 10ndash15 ww aqueous solution toattain workable 300ndash600 centipoises viscosityOpadry II category consisting HPMC and polysaccha-
rides was introduced to increase productivity The mostsignificant recent advances in the development of fully for-mulated aqueous film coatings have been the introductionof new film coatings based on polyvinyl alcohol (PVA)and sodium carboxymethylcellulose (NaCMC) PVA-basedfilms are known to have relatively low permeability formoisture vapour and oxygen whereas NaCMC-based coat-ings are glossy and have low oxygen permeability andrelatively high permeability for water vapourOpadry aqueous moisture barrier (AMB) and Opadry II
85 series are two proprietary families of PVA-based prod-ucts that were commercialized in the mid to-late 1990sThe Opadry AMB formulation were optimized to providethe lowest moisture vapour transmission rate Opadry II85 products give moisture vapour transmission rate almostas low as Opadry AMB but can be applied at significantlyhigher spray ratesFilm coatings based on PVA and NaCMC offer various
advantages Now moisture-sensitive drugs can be coatedin an aqueous coating process by PVA-based coatingsNaCMC based coatings provide demonstrable oxygenbarrier properties and excellent aesthetic characteristics(Porter and Felton 2010)
Supercelltrade Coating TechnologyThe ldquostandardrdquo practice of tablet coating often delivers anon-homogenous product Because the tablets are loadedin large rotating pans and vented for hot air drying edgesof tablets can get grounded off and intagliation can getfilled in by coating material leading to uneven coating onedgescorners and tablet faces This inaccuracy limits theuse of modified release coatings In a laboratory it is nec-essary to coat several kilograms of tablets at one timemaking RampD of a tablet dosage form costly and difficultFurther extremely hygroscopic as well as flat or other
oddly shaped tablets cannot be coated using present tech-nology so SCT (Niro Pharma Systems) technology uses asmall modular design that accurately deposits controlledamounts of coating materials on friable and extremelyhygroscopic tablets SCTrsquos continuous small-batch capablecoating process is predictable and efficient In SCT thetablets are coated in batches ranging from 30 to 120 gramswhich linearly scale up to production capacity In this tech-nique the tablets are covered with the polymer spray in
the same direction as the hot air resulting in an efficientprocess Due to SCTrsquos unique air distribution plate designthe tablets move very quickly and predictably through thespray zone receiving only a small amount of coating perpass and therefore achieving higher coating accuracy Theprocess time is short in seconds or in minutes as opposedto hours and therefore gentler on the tablets (Systems2012)Supercelltrade Coating Technology may also be used for
coating of flat or highly oblong tablets or friable tabletsIn this process drying is very fast making it possible tocoat extremely hygroscopic tablets The deposition accu-racy is sufficiently high to layer API onto tablets and uni-form layers of taste masking or modified release coatingscan be applied consecutively within a single continuousbatchUnique features of super cell coating technology are
(1) Continuous coating(2) Short processing time(3) Flexible modular design(4) No scale-up to parameters(5) Batch size for RampD (Minimum size sim30 grams)(6) Enhancing technology(7) Multi-layer coating(8) Low humidity process suitable for moisture sensitivematerials
Syloidreg FP Silicas inPharmaceutical Film CoatingsRecently film coatings have also shown encouragingresults to enable the oral delivery of peptide therapeuticsSyloidreg FP silicas have been used as excipients in manypharmaceutical formulations due to their unique morphol-ogy The combined adsorption capacity porosity particlesize and greater surface area allow them to provide severalbenefits simultaneously which can expedite manufacturingand improve efficacy of the final dosage form Syloidreg FPsilica can be used in polymeric coating systems in combi-nation of vinylcellulose or acrylic polymers (13 Septem-ber 2010)In standard concentrationsmdashAddition of Syloidreg 244FP
silica to film coating provides following advantages-Improved spray propertiesElimination of the need for talcImprovement of suspension propertiesPrevention of valve cloggingMinimal settling in spray linesSmoothen tablet surfaceReduction of adhesionApplications Anti-tacking agent Oral peptide deliveryODT formulations Enteric coatings Sustained releasecoatings Controlled release coatings (Grace Discovery)In recent years there has been a growing focus on
conducting fundamental studies through the applicationof appropriate modelling techniques and novel analytical
J Pharm Sci Pharmacol 1 57ndash67 2014 65
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Film Coating Technology Past Present and Future Gaur et al
technologies In addition recent trends are directed towardimprovements in processing as well as development ofnovel release functionality The following section providesa review to some of these areas
PROCESS MODELLING SYSTEMS ANDTHEIR APPLICATIONSFilm coating process comprises various steps which canbe direct or indirect Direct parameters include air pres-sure and flow temperature of coating spray and tabletcore and spray rate The indirect parameters take accountof droplet size distribution and viscosity coating unifor-mity and thickness So different modelling systems havebeen proposed eg Digital video imaging Discrete ele-ment methodologies (DEM) Computational fluid dynam-ics (CFD)Discrete element method embodies different techniques
implying on a large number of small particles to figure outthe movement and their interaction In film coating pro-cedure DEM is used for estimating movement of tabletsand predicting the coating uniformity Computational fluiddynamics applies the principles of fluid mechanics for filmcoating process (Felton and Porter 2013 Felton 2007)The major application of process analytical technique is
that it is amenable to automation So it can be applied formonitoring and controlling various unit operations It canbe applied for product moisture content amount of coatingapplied endpoint of the process and properties of coatingeg porosity and densityHowever adaptation of PAT for coating process requires
positioning of sensors in unsuitable conditions whichcan have a bearing on sensor sensitivity So varioussophisticated analytical processes eg terahertz refractiveindex (TRI) and pulse imaging (TPI) near-infrared andraman spectroscopy (NIR) laser-induced breakdown spec-troscopy (LIBS) and confocal laser techniques can beapplied offline All of these techniques can also be usedonline since these are non-destructive except LIBSNIR methods can be employed for determining the coat-
ing amount to predict drug release rate in combinationwith multivariate analysis NIR spectroscopy can be usedto estimate an API in a coated tablet with plusmn 4 targetvalue in comparison to HPLC Major advantage of NIRspectroscopy is its non-invasiveness and rapidity Howeverit cannot be used with drugs in hydrate form Raman spec-troscopy is less sensitive to hydrates TPI technique can beused to determine the amount of coating in a side-ventedpan (Felton 2007 Felton and Porter 2013)
CONCLUSIONBased on the facts regarding film coating process we canemphasize that various recent trends may drive the indus-try closer to large scale adoption of dry powder coatingtechnologies for oral delivery First the current changes
in global austerity have pushed many pharmaceutical andbiotechnology companies to seriously examine manufac-turing costs The lower cost associated with dry powdercoating technology makes it attractive for both brand andgeneric companies seeking to reduce operating expensesAnother major driver in the future will be the needs of
advanced drug products specifically focused in the area ofcounterfeit resistance and amorphous formulation supportCounterfeit drugs are a major problem facing global phar-maceutical companies with steps being taken to protectthe supply chain and also develop visually differentiatedproducts Dry powder coating particularly electrostatic drypowder coating can be used to prepare novel identificationmarks onto drug products in a rapid cost effective mannerleading to enhanced brand identificationBeyond this the potential to eliminate the need for sol-
vents allows for more effective application of coatings tomoisture sensitive products This opens up unique oppor-tunities in the drug product design of amorphous systemsand may potentially play a role in future product designsGiven the potential of the technology academic researchwill continue in earnest as the pharmaceutical industrycontinues the adoption of the technology Over time anddriven by a number of different factors dry powder coatingappears poised to become a major pharmaceutical coatingtechnology in the future
Acknowledgment The authors wish to express thegratitude towards administrative authorities at ITSParamedical (Pharmacy) College Muradnagar Ghaziabadfor providing necessary support during collection of data
REFERENCESAulton M (ed) (1995) Mechanical properties of film coats Tay-lorampFrancis London
Bodmeier R and Paeratakul O (1994) Mechanical properties of dry andwet cellulosic and acrylic films prepared from aqueous colloidal polymerdispersions used in the coating of solid dosage forms PharmaceuticalResearch 11 882ndash88
Chen W Chang S-Y Kiang S Early W Paruchuri S and DesaiD (2008) The measurement of spray quality for pan coating processJ Pharm Innov 3 3ndash14
Chen W Chang S Y Kiang S Marchut A Lynberg O Wang JRao V Desai D Stamato H and Early W (2010) Modeling of pancoating process Prediction of tablet content uniformity and determinationof critical process parameters J Pharm Sci 99 3213ndash24
Cole G (1998) Pharmaceutical Coating Technology Taylor and FrancisLondon
Dillon R E Matheson L A and Bradford E B (1951) Sintering ofsynthetic latex particles Journal of Colloid Science 6 108ndash17
Felton L A (2007) Characterization of coating systems AAPS PharmSci Tech 8 112
Felton L A and Porter S C (2013) An update on pharmaceutical filmcoating for drug delivery Expert Opinion on Drug Delivery 10 421ndash35
Franz R and Doonan G (1983) Measuring the surface temperature oftablet beds using infrared thermometry Pharm Technol 7 55ndash67
66 J Pharm Sci Pharmacol 1 57ndash67 2014
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Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
Harris M R and Sellassie G (eds) (1997) Aqueous Polymeric Coat-ing for Modified Release Oral Dosage forms Marcel Dekker Inc NeyYork
Hogan J (1998) Pharmaceutical Coating Technology Taylor and FrancisLtd London
Lachman L Lieberman H A and Joseph L K (1989) The Theoryand Practice of Industrial Pharmacy vol 3 Varghese Publishing HouseMumbai
Lehmann K (ed) (1994) Coating of multiparticulates using polymericsolutions Formulation and process considerations Marcel Dekker IncNew York
Libermen H and Lachman L (2003) Pharmaceutical Dosage FormsTablets Marcel Dekker Inc NY Vols 1ndash3
Lipper R D Desai D and Kiang S (September 11ndash12 2006) CaseStudy Implementation of Design Space Concepts in Development of anActive-Coated Tablet In Real World Applications of PAT and QbD inDrug Process Development and Approval Bristol-Myers Squibb Pharma-ceutical Research Institute Arlington Virginia USA
Lippold B C and Monells P P (2001) Film formation reproducibilityof production and curing with respect to release stability of functionalcoatings from aqueous polymer dispersions Pharmazie 56 5ndash17
Malm C J and Waring C E (1937) Cellulose esters containing dicar-boxylic acid groups and process of making the same
Mazer T B Meyer G A Hwang S M Candler E L Drayer LR and Daab-Krzykowski A (1992) System for delivering an activesubstance for sustained release
Narang A K M Castoro J Varia S and Desai D (2011) Effect ofPro- and Anti-Oxidants on the Formation of Formyl Species in PVA- andPEG-Based Tablet Coating Material AAPS Washington D C USA
Narang A S Desai D and Badawy S (2012) Impact of excipientinteractions on solid dosage form stability Pharm Res 29 2660ndash83
Ogaji I and Nnoli O (2010) Film coating potential of okra gum usingparacetamol tablets as a model drug Asian J Pharm 4 130ndash34
Ogaji I J and Hoag S W (2011) Effect of grewia gum as a suspend-ing agent on ibuprofen pediatric formulation AAPS PharmSciTech 12507ndash13
Ogaji I J Okafor I S and Hoag S W (2013) Grewia gum as a poten-tial aqueous film coating agent I Some physicochemical characteristicsof fractions of grewia gum J Pharm Bioall Sci 5 53ndash60
Okutgen E Jordan M Hogan J E and Aulton M E (1991) Effectsof tablet core dimensional instability on the generation of internal stresses
within film coats part II Temperature and relative humidity variationwithin a tablet bed during aqueous film coating in an accela-cota DrugDevelopment and Industrial Pharmacy 17 1191ndash99
Opadryreg Complete Film Coating System Coating ParametersndashAqueous Formulas Colorcon Inc North America BPSI HoldingsLLC
Porter C (1990) Coating of Pharmaceutical Solid Dosage Forms MackPublishing Company Easton Pennsylvania
Porter S C (ed) (2011) Scale-Up of Film Coating Informa HealthcareNew York
Porter S C and Felton L A (2010) Techniques to assess film coat-ings and evaluate film-coated products Drug Development and IndustrialPharmacy 36 128ndash42
Rekhi G S Porter S C and Jambhekar S S (1995) Factors affectingthe release of propranolol hydrochloride from beads coated with aque-ous polymeric dispresions Drug Development and Industrial Pharmacy21 709ndash29
Sadeghi F Ford J L Rubinstein M and Rajabi-Siahboomi A R(2001) Study of drug release from pellets coated with surelease con-taining hydroxypropyl methylcellulose Drug Development and IndustrialPharmacy 27 419ndash30
Savage G V and Rhodes C T (1995) The sustained release coating ofsolid dosage forms A historical review Drug Development and Indus-trial Pharmacy 21 93ndash118
Seitz J A Swarbrick J and Boylan J C (1988) Aqueous film coat-ing Encyclopedia of Pharmaceutical Technology Marcel Dekker NewYork pp 337ndash49
Singh P Solanky T K Mudryya R Pfefferc R and Davea R (2001)Estimation of coating time in the magnetically assisted impaction coatingprocess Powder Technology 121 159ndash67
Syloidreg FP silica excipientsmdashmore than just Silica (Belgium Fred Mon-suur Grace Davison Discovery Sciences) (13 September 2010)
Systems GNP (2012) SUPERCELLtrade Tablet Coating Technology (SCT)Niro Inc 9165 Rumsey Road Columbia MD 21045 USA
Wu C and McGinity J W (2001) Influence of Ibuprofen as a solid-state plasticizer in Eudragit RS 30D on the physicochemical propertiesof coated beads AAPS PharmSciTech 2 1ndash9
Zheng W and McGinity J W (2003) Influence of Eudragit NE 30 Dblended with Eudragit L 30 D-55 on the release of phenylpropanolaminehydrochloride from coated pellets Drug Development and IndustrialPharmacy 29 357ndash66
J Pharm Sci Pharmacol 1 57ndash67 2014 67
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Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
living cells and coating of tablets as well as capsules Theprinciple of electrostatic powder coating states that spray-ing of a mixture of finely grounded particles and polymersonto a substrate surface without using any solvent and thenheating the substrate for curing in oven until the powdermixture is fused into filmAccording to the charging mechanism there are two
types of spraying units namely(a) Corona charging(b) Tribo charging
Magnetically Assisted Impaction CoatingIn this technique the particles are assumed to stay in afluidized state where the distribution of velocities is aMaxwellndashBoltzmann type It is assumed that the collisionsoccurring among the particles are important for impingingthe guest particles onto the surface of host particles therebymaking a transient surface on the host particles The coatingtime depends on various parameters eg properties of thehost and guest particles number of host particles height ofthe fluidized bed and ratio of the host and guest particlesdiameters For a particular coating time the bed height andparticle size should be optimum (Singh et al 2001)
Film Formation Mechanisms inDry Powder CoatingFilm formation takes place by a process of evaporationcoalescence and sintering which are influenced by pro-cess and formulation considerations During the dry pow-der coating process the substrates are often heated abovethe glass transition temperature of the layering materialsso that the coating materials soften and adhere to the sub-strate For conventional film coating spreading and adher-ence is not limited by mobility however powder systemsmay become limited by mobility particularly when liquidlevels are reduced to the point where solid particle defor-mation becomes rate limiting This introduces a series ofconstraints related to mechanical and thermal propertiesof the coating formulation Coalescence and film forma-tion are therefore dependent on these properties as wellAs such glass transition temperature and plastic deforma-tion characteristics of the coating materials are paramountto the success of the process Many pharmaceutical coat-ing materials are amorphous polymers exhibiting a glasstransition temperature related to the change from a glassto a super cooled liquid On transition which occurs at aspecific temperature mobility of the system increases sig-nificantly The greater mobility allows for molecular rear-rangement and alters the plastic deformation characteristicsof the materialsThe mechanism of film formation of the powders lay-
ered onto the solid cores ismdashsummarized as (Felton andPorter 2013 Felton 2007)(i) Coalescence and sintering of the particles of the poly-meric materials in a process that involves the partial fusionof the polymer
(ii) Levelling of the coating material includes densifica-tion of the layer with reduction of the empty spaces andsmoothening of the surface(iii) Cooling of the layer and hardening of the coating
Based on FunctionProtective CoatingsThin films of water soluble polymers are often appliedfor taste or odour masking or to improve the stabilityof moisture sensitive products or for better mechanicalresistance of the product during handling Such protectivecoatings need to remain intact for the short time of swal-lowing and after that they should immediately dissolve toensure immediate drug release These polymers are water-soluble eg cellulose ethers (eg hydroxypropyl methyl-cellulose (HPMC)) polyvinyl acetate (PVA) or polyvinylpyrrolidone (PVP) Eudragitreg E is a methacrylic copoly-mer insoluble in saliva but rapidly dissolves in the acidicpH of the stomach Sometimes enteric polymers eg shel-lac can also be applied at very low concentration whichgives very low film thickness insufficient to provide gastricresistance and disintegrates in the stomach within 30 min(Lehmann 1994 Porter 1990 Porter 2011)
Functional CoatingsFilm coatings which are applied to achieve a desiredrelease profile are usually termed modified-release orfunctional coatings Those intended to protect the drugfrom the acidic environment of the stomach are entericcoatings Extended release coatings in contrast areintended to control the release of the drug over a prolongedperiod of time (Porter 1990)Enteric Coatings Enteric coatings are prepared from
gastric resistant polymers which remain intact in stom-ach but immediately dissolve in small intestine Themost effective enteric polymers contain many carboxylicgroups with a pKa of 3ndash5 Therefore they will dissoci-ate and dissolve only when the pH rises above this value(Porter 2011 Lehmann 1994) Before the synthetic poly-mers were introduced to the market shellac a naturalpolymer was one of the main polymer used for this pur-pose Cellulose acetate phthalate (CAP) was the first syn-thetic polymer described in 1937 which soon gained highpopularity as a gastric resistant polymer Later polyvinylacetate phthalate (PVAP) and hydroxypropyl methylcel-lulose phthalate (HPMCP) were preferred due to theirlower permeability in the gastric fluid and improved sta-bility against hydrolysis Today methacrylate copolymersEudragitreg L and S are two of the most widely used poly-mers for this purpose (Malm and Waring 1937 Zheng andMcGinity 2003)Extended Release Coatings The patient compliance is
usually inversely proportional with the frequency of drugadministration especially when multiple daily administra-tions are necessary to maintain constant blood levels of the
J Pharm Sci Pharmacol 1 57ndash67 2014 61
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Film Coating Technology Past Present and Future Gaur et al
drug Therefore extended release polymers were devel-oped which are able to provide a sustained action by acontrolled release over time Waxes and some natural poly-mers were already discovered earlier to be useful to pro-long the drug release if coated onto the solid dosage formsMostly their mechanism of performance is based on slowdegradation or erosion Polymers for extended release arein general insoluble in water over the entire pH range Thedrug release is thus controlled by diffusion through thehydrated polymer or through cracks or water-filled poresThere are still only few polymers available on the mar-ket for extended release eg cellulose acetate ethylcel-lulose or the methacrylic acid copolymers Eudragitreg RSRL and NE Combinations of ethylcellulose with waxeswater-soluble or enteric polymers were investigated toachieve extended drug release for drug with varying oreven pH-dependent solubilities Synthetic polymers how-ever do not fit into the overall product concept of phyto-pharmaceutical products or as for nutraceuticals they arenot approved Therefore several attempts were undertakento achieve sustained drug release by using only naturalpolymers The drug release from silk fibroin coated tabletsafter cross-linking with a carbodiimide was extended toseveral hours (Savage and Rhodes 1995) Shellac is alsoable to provide prolonged drug release at higher coatinglevels or as matrix forming material However there is nodrug release for such systems in the gastric medium due tothe enteric property of shellac Zein as a water-insolublenatural polymer is an alternative for extended drug releaseespecially in combination with an additional enteric top-coat (Mazer et al 1992)
Active CoatingIn it the drug is embedded into the coat to formulate afixed dose combination or to modify the release profileThe beadlets are then filled into capsules however the vol-ume limitation of capsules makes it an unsuitable approachfor higher dose drugs (Seitz et al 1988)This is particularly useful for the drugs unstable at
high mechanical stress In an active coating process com-mon pharmaceutical operations can be avoided Drugs thatundergo acid or base catalysed degradation have been sta-bilized by this technique It gives relatively high drug toexcipient ratio than encapsulating such molecules in thetablet core Fixed dose combinations can be formulated bythis approach (Hogan 1998)The primary concerns of an active coating process
are end-point content uniformity efficiency and stabilitywhich are either directly or indirectly affected by pro-cess parameters such as rate of spraying inlet air temper-ature residual moisture pan speed atomisation pressureand drug properties The end point is estimated by the gainin tablet weight or quantity of coating suspension sprayedPeriodically tablets are sampled and analysed for the drugamount (Lipper et al September 11ndash12 2006) Severalmathematical models have been proposed to ascertain a
correlation between coating parameters and content unifor-mity but the model proposed by Cheng et al has confirmedto be most robust (Chen et al 2010 Chen et al 2008)Coating time is also an important parameter since a
longer coating time results in better content uniformity butit makes the process not amenable for a high volume prod-uct On the other hand too short coating time can lead toincomplete coating process Spray zone width should notbe too narrow or too wide If the tablet bed has not beenappropriately covered then there will be either unsprayedsubstrate or unused deposit of coating solutionCoating process should yield the tablets having required
polymorphic forms and the coating suspension shouldcrystallise after drying The stability is adversely affectedif the coating stays in amorphous state The polymor-phism also depends on coating excipients eg plasticisers(Narang et al 2011 Narang et al 2012 Chen et al 2010Chen et al 2008)Effectiveness of the Active Coating Process The coat-
ing efficiency improves significantly when the droplet sizeis smaller than 10 m By appropriate selection of atomiz-ing and pattern air volume the fraction of droplets smallerthan 10 microns can be reduced to improve the overallefficiency of the coating process Factors governing themsuch as high ratios of the suspension spray rate to atom-ization air flow rate suspension spray rate to pattern airflow rate or atomization air flow rate to pattern air flowrate can improve the coating efficiency
FILM COATING FORMULATIONCOMPONENTSPolymersA polymer is a large molecules made up of many identicalsubunits of monomers (Table I)
Immediate Release Coating PolymersCellulose Derivates The most widely used cellulosic
polymers is Hydroxypropyl Methyl Cellulose (HPMC)which is readily soluble in aqueous medium and forms flex-ible strong films which adhere to the core Other examplesMC (Methyl Cellulose) and HPC (Hydroxypropyl Cellu-lose) (Hogan 1998 Lachman et al 1989 Lehmann 1994)Vinyl Derivates The most widely used vinyl polymer
is Poly Vinyl Pyrrolidone (PVP) however it has inherenttackiness For better film coating its copolymer with vinylacetate is used
Modified Release Coating PolymersExtended Release Coating Polymers They are dis-
solved in organic solvent or dispersed in aqueous mediumeg highly substituted cellulose making them water-insoluble example Ethyl Cellulose (EC)Enteric Coating Polymers
(a) Methacrylic Acid The presence of carboxylic acidgroups renders this class to be insoluble in water at low pH
62 J Pharm Sci Pharmacol 1 57ndash67 2014
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Gaur et al Film Coating Technology Past Present and Future
Table I Film coatings are available based on the following polymeric materials
pH Independent polymer for rapidly disintegrating film coating
1 Neutral co-polymer Film coat E30D For film coating of tabletspellets granules powders
Natural polymer
1 Xanthan gum Film coating of tablets2 Pectin Film coating of tablets3 Chitosan Film coating of tablets4 Okra gum Film coating of tablets5 Grewia gum Film coating of tablets
(stomach) but as the pH rises towards neutrality in upperpart of the small intestine the coating gradually dissolvesExample Eudragit(b) Phthalate esters These polymers contain free car-boxylic acid making them acid insoluble however in intes-tine they become deprotonated and dissolves in basicmedia They are also called enteric coating polymers egCellulose acetate phthalate (CAP) Enteric coating poly-mers can be classified into 3 groups based on chemicalcompositions as listed below
The solubility of the polymers depend on the numberof carboxylic acid groups Enteric formulations shouldhave less than 10 drug release in 2 hours during acidstage The completion of the drug release in the continu-ation testing in the buffer stage should take place within45 min Classification of Polymers Based on Derivatives(Lehmann 1994 Libermen and Lachman 2003 Malm
J Pharm Sci Pharmacol 1 57ndash67 2014 63
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Copyright American Scientific Publishers
Film Coating Technology Past Present and Future Gaur et al
and Waring 1937 Sadeghi et al 2001 Ogaji and Nnoli2010 Ogaji and Hoag 2011 Ogaji et al 2013)
PlasticizersPlasticizers are relatively low molecular weight materialswhich are used as additives in pharmaceutical coating for-mulations to reduce the brittleness and increase the flex-ibility of the resulting film They act by weakening intermolecular attraction between polymer chains and facili-tating coalescence of discrete polymer spheres of aque-ous dispersed systems during film formation Adhesive andmechanical properties of the coating and subsequent drugrelease are dependent on the concentration of plasticizersto a great extent Plasticizers are non volatile componentsand therefore are responsible for the weight gain of dosageforms during coating A plasticizer has to be miscible andfulfil all the compatibility parameters with the polymerbeing usedAn important consideration is the content of plasticizer
as it can affect the glass transition temperature (Tg) soit should be experimentally determined by evaluating thechanges in Tg of polymer as the plasticizer content isincreased Tg is the temperature for amorphous polymersat which the behaviour of the film changes from hard andbrittle to soft and elastic An effective plasticizing agentis one which exhibits a greater decrease in the Tg of thefilm Changes in the mechanical properties of the poly-meric film are an indication of plasticizer efficacy (Seitzet al 1988 Wu and McGinity 2001)Plasticizers are classified into three groups
Anti-AdherentsAnti-adherents are used as additives to avoid agglomera-tion of the substrates during both the coating process andon subsequent storage One of the most common anti-adherents used in pharmaceutical coatings is talc but sinceit has to be used at high concentration it creates pro-cessing challenges including clogging of the spray noz-zle during coating and particle sedimentation It tends todecrease water vapour permeability and also the dissolu-tion rate of drugs due to its hydrophobic nature It alsoaffects the mechanical and adhesive properties of polymerfilms so now Glyceryl monostearate has been found as analternative to talc
Opacifying AgentsColorantsPigments deliver elegance and stability enhancement tothe solid dosage form Water-insoluble lakes and the iron
oxides are most commonly used pigments Colour migra-tion and stability issues have diminished the use of thewater-soluble dyes in film coating Pigments can signifi-cantly affect the mechanical and permeability properties ofthe film An inverse relation-ship between film-tablet adhe-sion and the particle size of the pigment has been reportedStudies have shown that the shape of the pigment par-ticle and the extent of polymer-particle interaction influ-ence the elastic modulus of polymeric films and surfacepolarity of pigments influences drug release In additionchemical incompatibilities between the pigment and thepolymer have also been reported predominantly relatedto the size and surface charge of the components andthe pH of the medium One important concept relevantto pigments is the critical pigment volume concentration(CPVC) this is the maximum concentration (based on vol-ume) of the insoluble material that can be incorporated intoa film without compromising film properties If the CPVCis exceeded insufficient polymer is present to surroundall the insoluble particles resulting in marked changes indifferent properties of the film Colorants are mainly clas-sified in to three types(i) Organic dyes and their lakes eg Erythrosine tar-trazine Sunset yellow(ii) Inorganic colours eg Iron oxide yellow red andblack titanium dioxide talc(iii) Natural colours eg Riboflavin Anthocyanins andCarmine
SolventsVehiclesThe key function of a solvent system is to dissolve ordisperse the polymers and other additivesThe major classes of solvents being used are aqueous
(Water) and Nonaqueous (Alcohols Ketones Esters Chlo-rinated hydrocarbons) Because of environmental and eco-nomic concerns water is the most commonly used solvent
Miscellaneous Coating Solution ComponentsSolid dosage form may be incorporated with several spe-cial materials such asFlavours and sweeteners are added to mask unpleasant
odours or to develop the taste eg fruit spirits (organicsolvent) aspartame water soluble pineapple flavourSurfactants are ancillary to stabilize immiscible or insol-
uble ingredients in the coating They facilitate substratewettability and promote coalescence of polymeric materialover the substratersquos surface eg Spans Tweens etcAntioxidants are incorporated to stabilize a dye system
to oxidation and colour change eg oximes phenols etcAntimicrobials are added to inhibit microbial growth
in the coating composition Various cellulosic materialsare mainly prone to microbial growth and they can notbe stored in solution form eg Carbamates alkylisothia-zloinone benzothiazoles etc
64 J Pharm Sci Pharmacol 1 57ndash67 2014
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Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
CURRENT TRENDS IN FILM COATING ANDFUTURE DIRECTIONSOpadry formulations provided numerous advantages ver-sus the use of individual raw materials including thereduction of the number of raw materials for Qualitycontrol testing reduced preparation time reliable colour-matched formulations tremendous appearance and excel-lent mechanical parameters However opadry dispersionsolids must be stored as 10ndash15 ww aqueous solution toattain workable 300ndash600 centipoises viscosityOpadry II category consisting HPMC and polysaccha-
rides was introduced to increase productivity The mostsignificant recent advances in the development of fully for-mulated aqueous film coatings have been the introductionof new film coatings based on polyvinyl alcohol (PVA)and sodium carboxymethylcellulose (NaCMC) PVA-basedfilms are known to have relatively low permeability formoisture vapour and oxygen whereas NaCMC-based coat-ings are glossy and have low oxygen permeability andrelatively high permeability for water vapourOpadry aqueous moisture barrier (AMB) and Opadry II
85 series are two proprietary families of PVA-based prod-ucts that were commercialized in the mid to-late 1990sThe Opadry AMB formulation were optimized to providethe lowest moisture vapour transmission rate Opadry II85 products give moisture vapour transmission rate almostas low as Opadry AMB but can be applied at significantlyhigher spray ratesFilm coatings based on PVA and NaCMC offer various
advantages Now moisture-sensitive drugs can be coatedin an aqueous coating process by PVA-based coatingsNaCMC based coatings provide demonstrable oxygenbarrier properties and excellent aesthetic characteristics(Porter and Felton 2010)
Supercelltrade Coating TechnologyThe ldquostandardrdquo practice of tablet coating often delivers anon-homogenous product Because the tablets are loadedin large rotating pans and vented for hot air drying edgesof tablets can get grounded off and intagliation can getfilled in by coating material leading to uneven coating onedgescorners and tablet faces This inaccuracy limits theuse of modified release coatings In a laboratory it is nec-essary to coat several kilograms of tablets at one timemaking RampD of a tablet dosage form costly and difficultFurther extremely hygroscopic as well as flat or other
oddly shaped tablets cannot be coated using present tech-nology so SCT (Niro Pharma Systems) technology uses asmall modular design that accurately deposits controlledamounts of coating materials on friable and extremelyhygroscopic tablets SCTrsquos continuous small-batch capablecoating process is predictable and efficient In SCT thetablets are coated in batches ranging from 30 to 120 gramswhich linearly scale up to production capacity In this tech-nique the tablets are covered with the polymer spray in
the same direction as the hot air resulting in an efficientprocess Due to SCTrsquos unique air distribution plate designthe tablets move very quickly and predictably through thespray zone receiving only a small amount of coating perpass and therefore achieving higher coating accuracy Theprocess time is short in seconds or in minutes as opposedto hours and therefore gentler on the tablets (Systems2012)Supercelltrade Coating Technology may also be used for
coating of flat or highly oblong tablets or friable tabletsIn this process drying is very fast making it possible tocoat extremely hygroscopic tablets The deposition accu-racy is sufficiently high to layer API onto tablets and uni-form layers of taste masking or modified release coatingscan be applied consecutively within a single continuousbatchUnique features of super cell coating technology are
(1) Continuous coating(2) Short processing time(3) Flexible modular design(4) No scale-up to parameters(5) Batch size for RampD (Minimum size sim30 grams)(6) Enhancing technology(7) Multi-layer coating(8) Low humidity process suitable for moisture sensitivematerials
Syloidreg FP Silicas inPharmaceutical Film CoatingsRecently film coatings have also shown encouragingresults to enable the oral delivery of peptide therapeuticsSyloidreg FP silicas have been used as excipients in manypharmaceutical formulations due to their unique morphol-ogy The combined adsorption capacity porosity particlesize and greater surface area allow them to provide severalbenefits simultaneously which can expedite manufacturingand improve efficacy of the final dosage form Syloidreg FPsilica can be used in polymeric coating systems in combi-nation of vinylcellulose or acrylic polymers (13 Septem-ber 2010)In standard concentrationsmdashAddition of Syloidreg 244FP
silica to film coating provides following advantages-Improved spray propertiesElimination of the need for talcImprovement of suspension propertiesPrevention of valve cloggingMinimal settling in spray linesSmoothen tablet surfaceReduction of adhesionApplications Anti-tacking agent Oral peptide deliveryODT formulations Enteric coatings Sustained releasecoatings Controlled release coatings (Grace Discovery)In recent years there has been a growing focus on
conducting fundamental studies through the applicationof appropriate modelling techniques and novel analytical
J Pharm Sci Pharmacol 1 57ndash67 2014 65
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Film Coating Technology Past Present and Future Gaur et al
technologies In addition recent trends are directed towardimprovements in processing as well as development ofnovel release functionality The following section providesa review to some of these areas
PROCESS MODELLING SYSTEMS ANDTHEIR APPLICATIONSFilm coating process comprises various steps which canbe direct or indirect Direct parameters include air pres-sure and flow temperature of coating spray and tabletcore and spray rate The indirect parameters take accountof droplet size distribution and viscosity coating unifor-mity and thickness So different modelling systems havebeen proposed eg Digital video imaging Discrete ele-ment methodologies (DEM) Computational fluid dynam-ics (CFD)Discrete element method embodies different techniques
implying on a large number of small particles to figure outthe movement and their interaction In film coating pro-cedure DEM is used for estimating movement of tabletsand predicting the coating uniformity Computational fluiddynamics applies the principles of fluid mechanics for filmcoating process (Felton and Porter 2013 Felton 2007)The major application of process analytical technique is
that it is amenable to automation So it can be applied formonitoring and controlling various unit operations It canbe applied for product moisture content amount of coatingapplied endpoint of the process and properties of coatingeg porosity and densityHowever adaptation of PAT for coating process requires
positioning of sensors in unsuitable conditions whichcan have a bearing on sensor sensitivity So varioussophisticated analytical processes eg terahertz refractiveindex (TRI) and pulse imaging (TPI) near-infrared andraman spectroscopy (NIR) laser-induced breakdown spec-troscopy (LIBS) and confocal laser techniques can beapplied offline All of these techniques can also be usedonline since these are non-destructive except LIBSNIR methods can be employed for determining the coat-
ing amount to predict drug release rate in combinationwith multivariate analysis NIR spectroscopy can be usedto estimate an API in a coated tablet with plusmn 4 targetvalue in comparison to HPLC Major advantage of NIRspectroscopy is its non-invasiveness and rapidity Howeverit cannot be used with drugs in hydrate form Raman spec-troscopy is less sensitive to hydrates TPI technique can beused to determine the amount of coating in a side-ventedpan (Felton 2007 Felton and Porter 2013)
CONCLUSIONBased on the facts regarding film coating process we canemphasize that various recent trends may drive the indus-try closer to large scale adoption of dry powder coatingtechnologies for oral delivery First the current changes
in global austerity have pushed many pharmaceutical andbiotechnology companies to seriously examine manufac-turing costs The lower cost associated with dry powdercoating technology makes it attractive for both brand andgeneric companies seeking to reduce operating expensesAnother major driver in the future will be the needs of
advanced drug products specifically focused in the area ofcounterfeit resistance and amorphous formulation supportCounterfeit drugs are a major problem facing global phar-maceutical companies with steps being taken to protectthe supply chain and also develop visually differentiatedproducts Dry powder coating particularly electrostatic drypowder coating can be used to prepare novel identificationmarks onto drug products in a rapid cost effective mannerleading to enhanced brand identificationBeyond this the potential to eliminate the need for sol-
vents allows for more effective application of coatings tomoisture sensitive products This opens up unique oppor-tunities in the drug product design of amorphous systemsand may potentially play a role in future product designsGiven the potential of the technology academic researchwill continue in earnest as the pharmaceutical industrycontinues the adoption of the technology Over time anddriven by a number of different factors dry powder coatingappears poised to become a major pharmaceutical coatingtechnology in the future
Acknowledgment The authors wish to express thegratitude towards administrative authorities at ITSParamedical (Pharmacy) College Muradnagar Ghaziabadfor providing necessary support during collection of data
REFERENCESAulton M (ed) (1995) Mechanical properties of film coats Tay-lorampFrancis London
Bodmeier R and Paeratakul O (1994) Mechanical properties of dry andwet cellulosic and acrylic films prepared from aqueous colloidal polymerdispersions used in the coating of solid dosage forms PharmaceuticalResearch 11 882ndash88
Chen W Chang S-Y Kiang S Early W Paruchuri S and DesaiD (2008) The measurement of spray quality for pan coating processJ Pharm Innov 3 3ndash14
Chen W Chang S Y Kiang S Marchut A Lynberg O Wang JRao V Desai D Stamato H and Early W (2010) Modeling of pancoating process Prediction of tablet content uniformity and determinationof critical process parameters J Pharm Sci 99 3213ndash24
Cole G (1998) Pharmaceutical Coating Technology Taylor and FrancisLondon
Dillon R E Matheson L A and Bradford E B (1951) Sintering ofsynthetic latex particles Journal of Colloid Science 6 108ndash17
Felton L A (2007) Characterization of coating systems AAPS PharmSci Tech 8 112
Felton L A and Porter S C (2013) An update on pharmaceutical filmcoating for drug delivery Expert Opinion on Drug Delivery 10 421ndash35
Franz R and Doonan G (1983) Measuring the surface temperature oftablet beds using infrared thermometry Pharm Technol 7 55ndash67
66 J Pharm Sci Pharmacol 1 57ndash67 2014
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
Harris M R and Sellassie G (eds) (1997) Aqueous Polymeric Coat-ing for Modified Release Oral Dosage forms Marcel Dekker Inc NeyYork
Hogan J (1998) Pharmaceutical Coating Technology Taylor and FrancisLtd London
Lachman L Lieberman H A and Joseph L K (1989) The Theoryand Practice of Industrial Pharmacy vol 3 Varghese Publishing HouseMumbai
Lehmann K (ed) (1994) Coating of multiparticulates using polymericsolutions Formulation and process considerations Marcel Dekker IncNew York
Libermen H and Lachman L (2003) Pharmaceutical Dosage FormsTablets Marcel Dekker Inc NY Vols 1ndash3
Lipper R D Desai D and Kiang S (September 11ndash12 2006) CaseStudy Implementation of Design Space Concepts in Development of anActive-Coated Tablet In Real World Applications of PAT and QbD inDrug Process Development and Approval Bristol-Myers Squibb Pharma-ceutical Research Institute Arlington Virginia USA
Lippold B C and Monells P P (2001) Film formation reproducibilityof production and curing with respect to release stability of functionalcoatings from aqueous polymer dispersions Pharmazie 56 5ndash17
Malm C J and Waring C E (1937) Cellulose esters containing dicar-boxylic acid groups and process of making the same
Mazer T B Meyer G A Hwang S M Candler E L Drayer LR and Daab-Krzykowski A (1992) System for delivering an activesubstance for sustained release
Narang A K M Castoro J Varia S and Desai D (2011) Effect ofPro- and Anti-Oxidants on the Formation of Formyl Species in PVA- andPEG-Based Tablet Coating Material AAPS Washington D C USA
Narang A S Desai D and Badawy S (2012) Impact of excipientinteractions on solid dosage form stability Pharm Res 29 2660ndash83
Ogaji I and Nnoli O (2010) Film coating potential of okra gum usingparacetamol tablets as a model drug Asian J Pharm 4 130ndash34
Ogaji I J and Hoag S W (2011) Effect of grewia gum as a suspend-ing agent on ibuprofen pediatric formulation AAPS PharmSciTech 12507ndash13
Ogaji I J Okafor I S and Hoag S W (2013) Grewia gum as a poten-tial aqueous film coating agent I Some physicochemical characteristicsof fractions of grewia gum J Pharm Bioall Sci 5 53ndash60
Okutgen E Jordan M Hogan J E and Aulton M E (1991) Effectsof tablet core dimensional instability on the generation of internal stresses
within film coats part II Temperature and relative humidity variationwithin a tablet bed during aqueous film coating in an accela-cota DrugDevelopment and Industrial Pharmacy 17 1191ndash99
Opadryreg Complete Film Coating System Coating ParametersndashAqueous Formulas Colorcon Inc North America BPSI HoldingsLLC
Porter C (1990) Coating of Pharmaceutical Solid Dosage Forms MackPublishing Company Easton Pennsylvania
Porter S C (ed) (2011) Scale-Up of Film Coating Informa HealthcareNew York
Porter S C and Felton L A (2010) Techniques to assess film coat-ings and evaluate film-coated products Drug Development and IndustrialPharmacy 36 128ndash42
Rekhi G S Porter S C and Jambhekar S S (1995) Factors affectingthe release of propranolol hydrochloride from beads coated with aque-ous polymeric dispresions Drug Development and Industrial Pharmacy21 709ndash29
Sadeghi F Ford J L Rubinstein M and Rajabi-Siahboomi A R(2001) Study of drug release from pellets coated with surelease con-taining hydroxypropyl methylcellulose Drug Development and IndustrialPharmacy 27 419ndash30
Savage G V and Rhodes C T (1995) The sustained release coating ofsolid dosage forms A historical review Drug Development and Indus-trial Pharmacy 21 93ndash118
Seitz J A Swarbrick J and Boylan J C (1988) Aqueous film coat-ing Encyclopedia of Pharmaceutical Technology Marcel Dekker NewYork pp 337ndash49
Singh P Solanky T K Mudryya R Pfefferc R and Davea R (2001)Estimation of coating time in the magnetically assisted impaction coatingprocess Powder Technology 121 159ndash67
Syloidreg FP silica excipientsmdashmore than just Silica (Belgium Fred Mon-suur Grace Davison Discovery Sciences) (13 September 2010)
Systems GNP (2012) SUPERCELLtrade Tablet Coating Technology (SCT)Niro Inc 9165 Rumsey Road Columbia MD 21045 USA
Wu C and McGinity J W (2001) Influence of Ibuprofen as a solid-state plasticizer in Eudragit RS 30D on the physicochemical propertiesof coated beads AAPS PharmSciTech 2 1ndash9
Zheng W and McGinity J W (2003) Influence of Eudragit NE 30 Dblended with Eudragit L 30 D-55 on the release of phenylpropanolaminehydrochloride from coated pellets Drug Development and IndustrialPharmacy 29 357ndash66
J Pharm Sci Pharmacol 1 57ndash67 2014 67
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Film Coating Technology Past Present and Future Gaur et al
drug Therefore extended release polymers were devel-oped which are able to provide a sustained action by acontrolled release over time Waxes and some natural poly-mers were already discovered earlier to be useful to pro-long the drug release if coated onto the solid dosage formsMostly their mechanism of performance is based on slowdegradation or erosion Polymers for extended release arein general insoluble in water over the entire pH range Thedrug release is thus controlled by diffusion through thehydrated polymer or through cracks or water-filled poresThere are still only few polymers available on the mar-ket for extended release eg cellulose acetate ethylcel-lulose or the methacrylic acid copolymers Eudragitreg RSRL and NE Combinations of ethylcellulose with waxeswater-soluble or enteric polymers were investigated toachieve extended drug release for drug with varying oreven pH-dependent solubilities Synthetic polymers how-ever do not fit into the overall product concept of phyto-pharmaceutical products or as for nutraceuticals they arenot approved Therefore several attempts were undertakento achieve sustained drug release by using only naturalpolymers The drug release from silk fibroin coated tabletsafter cross-linking with a carbodiimide was extended toseveral hours (Savage and Rhodes 1995) Shellac is alsoable to provide prolonged drug release at higher coatinglevels or as matrix forming material However there is nodrug release for such systems in the gastric medium due tothe enteric property of shellac Zein as a water-insolublenatural polymer is an alternative for extended drug releaseespecially in combination with an additional enteric top-coat (Mazer et al 1992)
Active CoatingIn it the drug is embedded into the coat to formulate afixed dose combination or to modify the release profileThe beadlets are then filled into capsules however the vol-ume limitation of capsules makes it an unsuitable approachfor higher dose drugs (Seitz et al 1988)This is particularly useful for the drugs unstable at
high mechanical stress In an active coating process com-mon pharmaceutical operations can be avoided Drugs thatundergo acid or base catalysed degradation have been sta-bilized by this technique It gives relatively high drug toexcipient ratio than encapsulating such molecules in thetablet core Fixed dose combinations can be formulated bythis approach (Hogan 1998)The primary concerns of an active coating process
are end-point content uniformity efficiency and stabilitywhich are either directly or indirectly affected by pro-cess parameters such as rate of spraying inlet air temper-ature residual moisture pan speed atomisation pressureand drug properties The end point is estimated by the gainin tablet weight or quantity of coating suspension sprayedPeriodically tablets are sampled and analysed for the drugamount (Lipper et al September 11ndash12 2006) Severalmathematical models have been proposed to ascertain a
correlation between coating parameters and content unifor-mity but the model proposed by Cheng et al has confirmedto be most robust (Chen et al 2010 Chen et al 2008)Coating time is also an important parameter since a
longer coating time results in better content uniformity butit makes the process not amenable for a high volume prod-uct On the other hand too short coating time can lead toincomplete coating process Spray zone width should notbe too narrow or too wide If the tablet bed has not beenappropriately covered then there will be either unsprayedsubstrate or unused deposit of coating solutionCoating process should yield the tablets having required
polymorphic forms and the coating suspension shouldcrystallise after drying The stability is adversely affectedif the coating stays in amorphous state The polymor-phism also depends on coating excipients eg plasticisers(Narang et al 2011 Narang et al 2012 Chen et al 2010Chen et al 2008)Effectiveness of the Active Coating Process The coat-
ing efficiency improves significantly when the droplet sizeis smaller than 10 m By appropriate selection of atomiz-ing and pattern air volume the fraction of droplets smallerthan 10 microns can be reduced to improve the overallefficiency of the coating process Factors governing themsuch as high ratios of the suspension spray rate to atom-ization air flow rate suspension spray rate to pattern airflow rate or atomization air flow rate to pattern air flowrate can improve the coating efficiency
FILM COATING FORMULATIONCOMPONENTSPolymersA polymer is a large molecules made up of many identicalsubunits of monomers (Table I)
Immediate Release Coating PolymersCellulose Derivates The most widely used cellulosic
polymers is Hydroxypropyl Methyl Cellulose (HPMC)which is readily soluble in aqueous medium and forms flex-ible strong films which adhere to the core Other examplesMC (Methyl Cellulose) and HPC (Hydroxypropyl Cellu-lose) (Hogan 1998 Lachman et al 1989 Lehmann 1994)Vinyl Derivates The most widely used vinyl polymer
is Poly Vinyl Pyrrolidone (PVP) however it has inherenttackiness For better film coating its copolymer with vinylacetate is used
Modified Release Coating PolymersExtended Release Coating Polymers They are dis-
solved in organic solvent or dispersed in aqueous mediumeg highly substituted cellulose making them water-insoluble example Ethyl Cellulose (EC)Enteric Coating Polymers
(a) Methacrylic Acid The presence of carboxylic acidgroups renders this class to be insoluble in water at low pH
62 J Pharm Sci Pharmacol 1 57ndash67 2014
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
Table I Film coatings are available based on the following polymeric materials
pH Independent polymer for rapidly disintegrating film coating
1 Neutral co-polymer Film coat E30D For film coating of tabletspellets granules powders
Natural polymer
1 Xanthan gum Film coating of tablets2 Pectin Film coating of tablets3 Chitosan Film coating of tablets4 Okra gum Film coating of tablets5 Grewia gum Film coating of tablets
(stomach) but as the pH rises towards neutrality in upperpart of the small intestine the coating gradually dissolvesExample Eudragit(b) Phthalate esters These polymers contain free car-boxylic acid making them acid insoluble however in intes-tine they become deprotonated and dissolves in basicmedia They are also called enteric coating polymers egCellulose acetate phthalate (CAP) Enteric coating poly-mers can be classified into 3 groups based on chemicalcompositions as listed below
The solubility of the polymers depend on the numberof carboxylic acid groups Enteric formulations shouldhave less than 10 drug release in 2 hours during acidstage The completion of the drug release in the continu-ation testing in the buffer stage should take place within45 min Classification of Polymers Based on Derivatives(Lehmann 1994 Libermen and Lachman 2003 Malm
J Pharm Sci Pharmacol 1 57ndash67 2014 63
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Copyright American Scientific Publishers
Film Coating Technology Past Present and Future Gaur et al
and Waring 1937 Sadeghi et al 2001 Ogaji and Nnoli2010 Ogaji and Hoag 2011 Ogaji et al 2013)
PlasticizersPlasticizers are relatively low molecular weight materialswhich are used as additives in pharmaceutical coating for-mulations to reduce the brittleness and increase the flex-ibility of the resulting film They act by weakening intermolecular attraction between polymer chains and facili-tating coalescence of discrete polymer spheres of aque-ous dispersed systems during film formation Adhesive andmechanical properties of the coating and subsequent drugrelease are dependent on the concentration of plasticizersto a great extent Plasticizers are non volatile componentsand therefore are responsible for the weight gain of dosageforms during coating A plasticizer has to be miscible andfulfil all the compatibility parameters with the polymerbeing usedAn important consideration is the content of plasticizer
as it can affect the glass transition temperature (Tg) soit should be experimentally determined by evaluating thechanges in Tg of polymer as the plasticizer content isincreased Tg is the temperature for amorphous polymersat which the behaviour of the film changes from hard andbrittle to soft and elastic An effective plasticizing agentis one which exhibits a greater decrease in the Tg of thefilm Changes in the mechanical properties of the poly-meric film are an indication of plasticizer efficacy (Seitzet al 1988 Wu and McGinity 2001)Plasticizers are classified into three groups
Anti-AdherentsAnti-adherents are used as additives to avoid agglomera-tion of the substrates during both the coating process andon subsequent storage One of the most common anti-adherents used in pharmaceutical coatings is talc but sinceit has to be used at high concentration it creates pro-cessing challenges including clogging of the spray noz-zle during coating and particle sedimentation It tends todecrease water vapour permeability and also the dissolu-tion rate of drugs due to its hydrophobic nature It alsoaffects the mechanical and adhesive properties of polymerfilms so now Glyceryl monostearate has been found as analternative to talc
Opacifying AgentsColorantsPigments deliver elegance and stability enhancement tothe solid dosage form Water-insoluble lakes and the iron
oxides are most commonly used pigments Colour migra-tion and stability issues have diminished the use of thewater-soluble dyes in film coating Pigments can signifi-cantly affect the mechanical and permeability properties ofthe film An inverse relation-ship between film-tablet adhe-sion and the particle size of the pigment has been reportedStudies have shown that the shape of the pigment par-ticle and the extent of polymer-particle interaction influ-ence the elastic modulus of polymeric films and surfacepolarity of pigments influences drug release In additionchemical incompatibilities between the pigment and thepolymer have also been reported predominantly relatedto the size and surface charge of the components andthe pH of the medium One important concept relevantto pigments is the critical pigment volume concentration(CPVC) this is the maximum concentration (based on vol-ume) of the insoluble material that can be incorporated intoa film without compromising film properties If the CPVCis exceeded insufficient polymer is present to surroundall the insoluble particles resulting in marked changes indifferent properties of the film Colorants are mainly clas-sified in to three types(i) Organic dyes and their lakes eg Erythrosine tar-trazine Sunset yellow(ii) Inorganic colours eg Iron oxide yellow red andblack titanium dioxide talc(iii) Natural colours eg Riboflavin Anthocyanins andCarmine
SolventsVehiclesThe key function of a solvent system is to dissolve ordisperse the polymers and other additivesThe major classes of solvents being used are aqueous
(Water) and Nonaqueous (Alcohols Ketones Esters Chlo-rinated hydrocarbons) Because of environmental and eco-nomic concerns water is the most commonly used solvent
Miscellaneous Coating Solution ComponentsSolid dosage form may be incorporated with several spe-cial materials such asFlavours and sweeteners are added to mask unpleasant
odours or to develop the taste eg fruit spirits (organicsolvent) aspartame water soluble pineapple flavourSurfactants are ancillary to stabilize immiscible or insol-
uble ingredients in the coating They facilitate substratewettability and promote coalescence of polymeric materialover the substratersquos surface eg Spans Tweens etcAntioxidants are incorporated to stabilize a dye system
to oxidation and colour change eg oximes phenols etcAntimicrobials are added to inhibit microbial growth
in the coating composition Various cellulosic materialsare mainly prone to microbial growth and they can notbe stored in solution form eg Carbamates alkylisothia-zloinone benzothiazoles etc
64 J Pharm Sci Pharmacol 1 57ndash67 2014
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
CURRENT TRENDS IN FILM COATING ANDFUTURE DIRECTIONSOpadry formulations provided numerous advantages ver-sus the use of individual raw materials including thereduction of the number of raw materials for Qualitycontrol testing reduced preparation time reliable colour-matched formulations tremendous appearance and excel-lent mechanical parameters However opadry dispersionsolids must be stored as 10ndash15 ww aqueous solution toattain workable 300ndash600 centipoises viscosityOpadry II category consisting HPMC and polysaccha-
rides was introduced to increase productivity The mostsignificant recent advances in the development of fully for-mulated aqueous film coatings have been the introductionof new film coatings based on polyvinyl alcohol (PVA)and sodium carboxymethylcellulose (NaCMC) PVA-basedfilms are known to have relatively low permeability formoisture vapour and oxygen whereas NaCMC-based coat-ings are glossy and have low oxygen permeability andrelatively high permeability for water vapourOpadry aqueous moisture barrier (AMB) and Opadry II
85 series are two proprietary families of PVA-based prod-ucts that were commercialized in the mid to-late 1990sThe Opadry AMB formulation were optimized to providethe lowest moisture vapour transmission rate Opadry II85 products give moisture vapour transmission rate almostas low as Opadry AMB but can be applied at significantlyhigher spray ratesFilm coatings based on PVA and NaCMC offer various
advantages Now moisture-sensitive drugs can be coatedin an aqueous coating process by PVA-based coatingsNaCMC based coatings provide demonstrable oxygenbarrier properties and excellent aesthetic characteristics(Porter and Felton 2010)
Supercelltrade Coating TechnologyThe ldquostandardrdquo practice of tablet coating often delivers anon-homogenous product Because the tablets are loadedin large rotating pans and vented for hot air drying edgesof tablets can get grounded off and intagliation can getfilled in by coating material leading to uneven coating onedgescorners and tablet faces This inaccuracy limits theuse of modified release coatings In a laboratory it is nec-essary to coat several kilograms of tablets at one timemaking RampD of a tablet dosage form costly and difficultFurther extremely hygroscopic as well as flat or other
oddly shaped tablets cannot be coated using present tech-nology so SCT (Niro Pharma Systems) technology uses asmall modular design that accurately deposits controlledamounts of coating materials on friable and extremelyhygroscopic tablets SCTrsquos continuous small-batch capablecoating process is predictable and efficient In SCT thetablets are coated in batches ranging from 30 to 120 gramswhich linearly scale up to production capacity In this tech-nique the tablets are covered with the polymer spray in
the same direction as the hot air resulting in an efficientprocess Due to SCTrsquos unique air distribution plate designthe tablets move very quickly and predictably through thespray zone receiving only a small amount of coating perpass and therefore achieving higher coating accuracy Theprocess time is short in seconds or in minutes as opposedto hours and therefore gentler on the tablets (Systems2012)Supercelltrade Coating Technology may also be used for
coating of flat or highly oblong tablets or friable tabletsIn this process drying is very fast making it possible tocoat extremely hygroscopic tablets The deposition accu-racy is sufficiently high to layer API onto tablets and uni-form layers of taste masking or modified release coatingscan be applied consecutively within a single continuousbatchUnique features of super cell coating technology are
(1) Continuous coating(2) Short processing time(3) Flexible modular design(4) No scale-up to parameters(5) Batch size for RampD (Minimum size sim30 grams)(6) Enhancing technology(7) Multi-layer coating(8) Low humidity process suitable for moisture sensitivematerials
Syloidreg FP Silicas inPharmaceutical Film CoatingsRecently film coatings have also shown encouragingresults to enable the oral delivery of peptide therapeuticsSyloidreg FP silicas have been used as excipients in manypharmaceutical formulations due to their unique morphol-ogy The combined adsorption capacity porosity particlesize and greater surface area allow them to provide severalbenefits simultaneously which can expedite manufacturingand improve efficacy of the final dosage form Syloidreg FPsilica can be used in polymeric coating systems in combi-nation of vinylcellulose or acrylic polymers (13 Septem-ber 2010)In standard concentrationsmdashAddition of Syloidreg 244FP
silica to film coating provides following advantages-Improved spray propertiesElimination of the need for talcImprovement of suspension propertiesPrevention of valve cloggingMinimal settling in spray linesSmoothen tablet surfaceReduction of adhesionApplications Anti-tacking agent Oral peptide deliveryODT formulations Enteric coatings Sustained releasecoatings Controlled release coatings (Grace Discovery)In recent years there has been a growing focus on
conducting fundamental studies through the applicationof appropriate modelling techniques and novel analytical
J Pharm Sci Pharmacol 1 57ndash67 2014 65
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Copyright American Scientific Publishers
Film Coating Technology Past Present and Future Gaur et al
technologies In addition recent trends are directed towardimprovements in processing as well as development ofnovel release functionality The following section providesa review to some of these areas
PROCESS MODELLING SYSTEMS ANDTHEIR APPLICATIONSFilm coating process comprises various steps which canbe direct or indirect Direct parameters include air pres-sure and flow temperature of coating spray and tabletcore and spray rate The indirect parameters take accountof droplet size distribution and viscosity coating unifor-mity and thickness So different modelling systems havebeen proposed eg Digital video imaging Discrete ele-ment methodologies (DEM) Computational fluid dynam-ics (CFD)Discrete element method embodies different techniques
implying on a large number of small particles to figure outthe movement and their interaction In film coating pro-cedure DEM is used for estimating movement of tabletsand predicting the coating uniformity Computational fluiddynamics applies the principles of fluid mechanics for filmcoating process (Felton and Porter 2013 Felton 2007)The major application of process analytical technique is
that it is amenable to automation So it can be applied formonitoring and controlling various unit operations It canbe applied for product moisture content amount of coatingapplied endpoint of the process and properties of coatingeg porosity and densityHowever adaptation of PAT for coating process requires
positioning of sensors in unsuitable conditions whichcan have a bearing on sensor sensitivity So varioussophisticated analytical processes eg terahertz refractiveindex (TRI) and pulse imaging (TPI) near-infrared andraman spectroscopy (NIR) laser-induced breakdown spec-troscopy (LIBS) and confocal laser techniques can beapplied offline All of these techniques can also be usedonline since these are non-destructive except LIBSNIR methods can be employed for determining the coat-
ing amount to predict drug release rate in combinationwith multivariate analysis NIR spectroscopy can be usedto estimate an API in a coated tablet with plusmn 4 targetvalue in comparison to HPLC Major advantage of NIRspectroscopy is its non-invasiveness and rapidity Howeverit cannot be used with drugs in hydrate form Raman spec-troscopy is less sensitive to hydrates TPI technique can beused to determine the amount of coating in a side-ventedpan (Felton 2007 Felton and Porter 2013)
CONCLUSIONBased on the facts regarding film coating process we canemphasize that various recent trends may drive the indus-try closer to large scale adoption of dry powder coatingtechnologies for oral delivery First the current changes
in global austerity have pushed many pharmaceutical andbiotechnology companies to seriously examine manufac-turing costs The lower cost associated with dry powdercoating technology makes it attractive for both brand andgeneric companies seeking to reduce operating expensesAnother major driver in the future will be the needs of
advanced drug products specifically focused in the area ofcounterfeit resistance and amorphous formulation supportCounterfeit drugs are a major problem facing global phar-maceutical companies with steps being taken to protectthe supply chain and also develop visually differentiatedproducts Dry powder coating particularly electrostatic drypowder coating can be used to prepare novel identificationmarks onto drug products in a rapid cost effective mannerleading to enhanced brand identificationBeyond this the potential to eliminate the need for sol-
vents allows for more effective application of coatings tomoisture sensitive products This opens up unique oppor-tunities in the drug product design of amorphous systemsand may potentially play a role in future product designsGiven the potential of the technology academic researchwill continue in earnest as the pharmaceutical industrycontinues the adoption of the technology Over time anddriven by a number of different factors dry powder coatingappears poised to become a major pharmaceutical coatingtechnology in the future
Acknowledgment The authors wish to express thegratitude towards administrative authorities at ITSParamedical (Pharmacy) College Muradnagar Ghaziabadfor providing necessary support during collection of data
REFERENCESAulton M (ed) (1995) Mechanical properties of film coats Tay-lorampFrancis London
Bodmeier R and Paeratakul O (1994) Mechanical properties of dry andwet cellulosic and acrylic films prepared from aqueous colloidal polymerdispersions used in the coating of solid dosage forms PharmaceuticalResearch 11 882ndash88
Chen W Chang S-Y Kiang S Early W Paruchuri S and DesaiD (2008) The measurement of spray quality for pan coating processJ Pharm Innov 3 3ndash14
Chen W Chang S Y Kiang S Marchut A Lynberg O Wang JRao V Desai D Stamato H and Early W (2010) Modeling of pancoating process Prediction of tablet content uniformity and determinationof critical process parameters J Pharm Sci 99 3213ndash24
Cole G (1998) Pharmaceutical Coating Technology Taylor and FrancisLondon
Dillon R E Matheson L A and Bradford E B (1951) Sintering ofsynthetic latex particles Journal of Colloid Science 6 108ndash17
Felton L A (2007) Characterization of coating systems AAPS PharmSci Tech 8 112
Felton L A and Porter S C (2013) An update on pharmaceutical filmcoating for drug delivery Expert Opinion on Drug Delivery 10 421ndash35
Franz R and Doonan G (1983) Measuring the surface temperature oftablet beds using infrared thermometry Pharm Technol 7 55ndash67
66 J Pharm Sci Pharmacol 1 57ndash67 2014
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
Harris M R and Sellassie G (eds) (1997) Aqueous Polymeric Coat-ing for Modified Release Oral Dosage forms Marcel Dekker Inc NeyYork
Hogan J (1998) Pharmaceutical Coating Technology Taylor and FrancisLtd London
Lachman L Lieberman H A and Joseph L K (1989) The Theoryand Practice of Industrial Pharmacy vol 3 Varghese Publishing HouseMumbai
Lehmann K (ed) (1994) Coating of multiparticulates using polymericsolutions Formulation and process considerations Marcel Dekker IncNew York
Libermen H and Lachman L (2003) Pharmaceutical Dosage FormsTablets Marcel Dekker Inc NY Vols 1ndash3
Lipper R D Desai D and Kiang S (September 11ndash12 2006) CaseStudy Implementation of Design Space Concepts in Development of anActive-Coated Tablet In Real World Applications of PAT and QbD inDrug Process Development and Approval Bristol-Myers Squibb Pharma-ceutical Research Institute Arlington Virginia USA
Lippold B C and Monells P P (2001) Film formation reproducibilityof production and curing with respect to release stability of functionalcoatings from aqueous polymer dispersions Pharmazie 56 5ndash17
Malm C J and Waring C E (1937) Cellulose esters containing dicar-boxylic acid groups and process of making the same
Mazer T B Meyer G A Hwang S M Candler E L Drayer LR and Daab-Krzykowski A (1992) System for delivering an activesubstance for sustained release
Narang A K M Castoro J Varia S and Desai D (2011) Effect ofPro- and Anti-Oxidants on the Formation of Formyl Species in PVA- andPEG-Based Tablet Coating Material AAPS Washington D C USA
Narang A S Desai D and Badawy S (2012) Impact of excipientinteractions on solid dosage form stability Pharm Res 29 2660ndash83
Ogaji I and Nnoli O (2010) Film coating potential of okra gum usingparacetamol tablets as a model drug Asian J Pharm 4 130ndash34
Ogaji I J and Hoag S W (2011) Effect of grewia gum as a suspend-ing agent on ibuprofen pediatric formulation AAPS PharmSciTech 12507ndash13
Ogaji I J Okafor I S and Hoag S W (2013) Grewia gum as a poten-tial aqueous film coating agent I Some physicochemical characteristicsof fractions of grewia gum J Pharm Bioall Sci 5 53ndash60
Okutgen E Jordan M Hogan J E and Aulton M E (1991) Effectsof tablet core dimensional instability on the generation of internal stresses
within film coats part II Temperature and relative humidity variationwithin a tablet bed during aqueous film coating in an accela-cota DrugDevelopment and Industrial Pharmacy 17 1191ndash99
Opadryreg Complete Film Coating System Coating ParametersndashAqueous Formulas Colorcon Inc North America BPSI HoldingsLLC
Porter C (1990) Coating of Pharmaceutical Solid Dosage Forms MackPublishing Company Easton Pennsylvania
Porter S C (ed) (2011) Scale-Up of Film Coating Informa HealthcareNew York
Porter S C and Felton L A (2010) Techniques to assess film coat-ings and evaluate film-coated products Drug Development and IndustrialPharmacy 36 128ndash42
Rekhi G S Porter S C and Jambhekar S S (1995) Factors affectingthe release of propranolol hydrochloride from beads coated with aque-ous polymeric dispresions Drug Development and Industrial Pharmacy21 709ndash29
Sadeghi F Ford J L Rubinstein M and Rajabi-Siahboomi A R(2001) Study of drug release from pellets coated with surelease con-taining hydroxypropyl methylcellulose Drug Development and IndustrialPharmacy 27 419ndash30
Savage G V and Rhodes C T (1995) The sustained release coating ofsolid dosage forms A historical review Drug Development and Indus-trial Pharmacy 21 93ndash118
Seitz J A Swarbrick J and Boylan J C (1988) Aqueous film coat-ing Encyclopedia of Pharmaceutical Technology Marcel Dekker NewYork pp 337ndash49
Singh P Solanky T K Mudryya R Pfefferc R and Davea R (2001)Estimation of coating time in the magnetically assisted impaction coatingprocess Powder Technology 121 159ndash67
Syloidreg FP silica excipientsmdashmore than just Silica (Belgium Fred Mon-suur Grace Davison Discovery Sciences) (13 September 2010)
Systems GNP (2012) SUPERCELLtrade Tablet Coating Technology (SCT)Niro Inc 9165 Rumsey Road Columbia MD 21045 USA
Wu C and McGinity J W (2001) Influence of Ibuprofen as a solid-state plasticizer in Eudragit RS 30D on the physicochemical propertiesof coated beads AAPS PharmSciTech 2 1ndash9
Zheng W and McGinity J W (2003) Influence of Eudragit NE 30 Dblended with Eudragit L 30 D-55 on the release of phenylpropanolaminehydrochloride from coated pellets Drug Development and IndustrialPharmacy 29 357ndash66
J Pharm Sci Pharmacol 1 57ndash67 2014 67
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Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
Table I Film coatings are available based on the following polymeric materials
pH Independent polymer for rapidly disintegrating film coating
1 Neutral co-polymer Film coat E30D For film coating of tabletspellets granules powders
Natural polymer
1 Xanthan gum Film coating of tablets2 Pectin Film coating of tablets3 Chitosan Film coating of tablets4 Okra gum Film coating of tablets5 Grewia gum Film coating of tablets
(stomach) but as the pH rises towards neutrality in upperpart of the small intestine the coating gradually dissolvesExample Eudragit(b) Phthalate esters These polymers contain free car-boxylic acid making them acid insoluble however in intes-tine they become deprotonated and dissolves in basicmedia They are also called enteric coating polymers egCellulose acetate phthalate (CAP) Enteric coating poly-mers can be classified into 3 groups based on chemicalcompositions as listed below
The solubility of the polymers depend on the numberof carboxylic acid groups Enteric formulations shouldhave less than 10 drug release in 2 hours during acidstage The completion of the drug release in the continu-ation testing in the buffer stage should take place within45 min Classification of Polymers Based on Derivatives(Lehmann 1994 Libermen and Lachman 2003 Malm
J Pharm Sci Pharmacol 1 57ndash67 2014 63
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Copyright American Scientific Publishers
Film Coating Technology Past Present and Future Gaur et al
and Waring 1937 Sadeghi et al 2001 Ogaji and Nnoli2010 Ogaji and Hoag 2011 Ogaji et al 2013)
PlasticizersPlasticizers are relatively low molecular weight materialswhich are used as additives in pharmaceutical coating for-mulations to reduce the brittleness and increase the flex-ibility of the resulting film They act by weakening intermolecular attraction between polymer chains and facili-tating coalescence of discrete polymer spheres of aque-ous dispersed systems during film formation Adhesive andmechanical properties of the coating and subsequent drugrelease are dependent on the concentration of plasticizersto a great extent Plasticizers are non volatile componentsand therefore are responsible for the weight gain of dosageforms during coating A plasticizer has to be miscible andfulfil all the compatibility parameters with the polymerbeing usedAn important consideration is the content of plasticizer
as it can affect the glass transition temperature (Tg) soit should be experimentally determined by evaluating thechanges in Tg of polymer as the plasticizer content isincreased Tg is the temperature for amorphous polymersat which the behaviour of the film changes from hard andbrittle to soft and elastic An effective plasticizing agentis one which exhibits a greater decrease in the Tg of thefilm Changes in the mechanical properties of the poly-meric film are an indication of plasticizer efficacy (Seitzet al 1988 Wu and McGinity 2001)Plasticizers are classified into three groups
Anti-AdherentsAnti-adherents are used as additives to avoid agglomera-tion of the substrates during both the coating process andon subsequent storage One of the most common anti-adherents used in pharmaceutical coatings is talc but sinceit has to be used at high concentration it creates pro-cessing challenges including clogging of the spray noz-zle during coating and particle sedimentation It tends todecrease water vapour permeability and also the dissolu-tion rate of drugs due to its hydrophobic nature It alsoaffects the mechanical and adhesive properties of polymerfilms so now Glyceryl monostearate has been found as analternative to talc
Opacifying AgentsColorantsPigments deliver elegance and stability enhancement tothe solid dosage form Water-insoluble lakes and the iron
oxides are most commonly used pigments Colour migra-tion and stability issues have diminished the use of thewater-soluble dyes in film coating Pigments can signifi-cantly affect the mechanical and permeability properties ofthe film An inverse relation-ship between film-tablet adhe-sion and the particle size of the pigment has been reportedStudies have shown that the shape of the pigment par-ticle and the extent of polymer-particle interaction influ-ence the elastic modulus of polymeric films and surfacepolarity of pigments influences drug release In additionchemical incompatibilities between the pigment and thepolymer have also been reported predominantly relatedto the size and surface charge of the components andthe pH of the medium One important concept relevantto pigments is the critical pigment volume concentration(CPVC) this is the maximum concentration (based on vol-ume) of the insoluble material that can be incorporated intoa film without compromising film properties If the CPVCis exceeded insufficient polymer is present to surroundall the insoluble particles resulting in marked changes indifferent properties of the film Colorants are mainly clas-sified in to three types(i) Organic dyes and their lakes eg Erythrosine tar-trazine Sunset yellow(ii) Inorganic colours eg Iron oxide yellow red andblack titanium dioxide talc(iii) Natural colours eg Riboflavin Anthocyanins andCarmine
SolventsVehiclesThe key function of a solvent system is to dissolve ordisperse the polymers and other additivesThe major classes of solvents being used are aqueous
(Water) and Nonaqueous (Alcohols Ketones Esters Chlo-rinated hydrocarbons) Because of environmental and eco-nomic concerns water is the most commonly used solvent
Miscellaneous Coating Solution ComponentsSolid dosage form may be incorporated with several spe-cial materials such asFlavours and sweeteners are added to mask unpleasant
odours or to develop the taste eg fruit spirits (organicsolvent) aspartame water soluble pineapple flavourSurfactants are ancillary to stabilize immiscible or insol-
uble ingredients in the coating They facilitate substratewettability and promote coalescence of polymeric materialover the substratersquos surface eg Spans Tweens etcAntioxidants are incorporated to stabilize a dye system
to oxidation and colour change eg oximes phenols etcAntimicrobials are added to inhibit microbial growth
in the coating composition Various cellulosic materialsare mainly prone to microbial growth and they can notbe stored in solution form eg Carbamates alkylisothia-zloinone benzothiazoles etc
64 J Pharm Sci Pharmacol 1 57ndash67 2014
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
CURRENT TRENDS IN FILM COATING ANDFUTURE DIRECTIONSOpadry formulations provided numerous advantages ver-sus the use of individual raw materials including thereduction of the number of raw materials for Qualitycontrol testing reduced preparation time reliable colour-matched formulations tremendous appearance and excel-lent mechanical parameters However opadry dispersionsolids must be stored as 10ndash15 ww aqueous solution toattain workable 300ndash600 centipoises viscosityOpadry II category consisting HPMC and polysaccha-
rides was introduced to increase productivity The mostsignificant recent advances in the development of fully for-mulated aqueous film coatings have been the introductionof new film coatings based on polyvinyl alcohol (PVA)and sodium carboxymethylcellulose (NaCMC) PVA-basedfilms are known to have relatively low permeability formoisture vapour and oxygen whereas NaCMC-based coat-ings are glossy and have low oxygen permeability andrelatively high permeability for water vapourOpadry aqueous moisture barrier (AMB) and Opadry II
85 series are two proprietary families of PVA-based prod-ucts that were commercialized in the mid to-late 1990sThe Opadry AMB formulation were optimized to providethe lowest moisture vapour transmission rate Opadry II85 products give moisture vapour transmission rate almostas low as Opadry AMB but can be applied at significantlyhigher spray ratesFilm coatings based on PVA and NaCMC offer various
advantages Now moisture-sensitive drugs can be coatedin an aqueous coating process by PVA-based coatingsNaCMC based coatings provide demonstrable oxygenbarrier properties and excellent aesthetic characteristics(Porter and Felton 2010)
Supercelltrade Coating TechnologyThe ldquostandardrdquo practice of tablet coating often delivers anon-homogenous product Because the tablets are loadedin large rotating pans and vented for hot air drying edgesof tablets can get grounded off and intagliation can getfilled in by coating material leading to uneven coating onedgescorners and tablet faces This inaccuracy limits theuse of modified release coatings In a laboratory it is nec-essary to coat several kilograms of tablets at one timemaking RampD of a tablet dosage form costly and difficultFurther extremely hygroscopic as well as flat or other
oddly shaped tablets cannot be coated using present tech-nology so SCT (Niro Pharma Systems) technology uses asmall modular design that accurately deposits controlledamounts of coating materials on friable and extremelyhygroscopic tablets SCTrsquos continuous small-batch capablecoating process is predictable and efficient In SCT thetablets are coated in batches ranging from 30 to 120 gramswhich linearly scale up to production capacity In this tech-nique the tablets are covered with the polymer spray in
the same direction as the hot air resulting in an efficientprocess Due to SCTrsquos unique air distribution plate designthe tablets move very quickly and predictably through thespray zone receiving only a small amount of coating perpass and therefore achieving higher coating accuracy Theprocess time is short in seconds or in minutes as opposedto hours and therefore gentler on the tablets (Systems2012)Supercelltrade Coating Technology may also be used for
coating of flat or highly oblong tablets or friable tabletsIn this process drying is very fast making it possible tocoat extremely hygroscopic tablets The deposition accu-racy is sufficiently high to layer API onto tablets and uni-form layers of taste masking or modified release coatingscan be applied consecutively within a single continuousbatchUnique features of super cell coating technology are
(1) Continuous coating(2) Short processing time(3) Flexible modular design(4) No scale-up to parameters(5) Batch size for RampD (Minimum size sim30 grams)(6) Enhancing technology(7) Multi-layer coating(8) Low humidity process suitable for moisture sensitivematerials
Syloidreg FP Silicas inPharmaceutical Film CoatingsRecently film coatings have also shown encouragingresults to enable the oral delivery of peptide therapeuticsSyloidreg FP silicas have been used as excipients in manypharmaceutical formulations due to their unique morphol-ogy The combined adsorption capacity porosity particlesize and greater surface area allow them to provide severalbenefits simultaneously which can expedite manufacturingand improve efficacy of the final dosage form Syloidreg FPsilica can be used in polymeric coating systems in combi-nation of vinylcellulose or acrylic polymers (13 Septem-ber 2010)In standard concentrationsmdashAddition of Syloidreg 244FP
silica to film coating provides following advantages-Improved spray propertiesElimination of the need for talcImprovement of suspension propertiesPrevention of valve cloggingMinimal settling in spray linesSmoothen tablet surfaceReduction of adhesionApplications Anti-tacking agent Oral peptide deliveryODT formulations Enteric coatings Sustained releasecoatings Controlled release coatings (Grace Discovery)In recent years there has been a growing focus on
conducting fundamental studies through the applicationof appropriate modelling techniques and novel analytical
J Pharm Sci Pharmacol 1 57ndash67 2014 65
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Film Coating Technology Past Present and Future Gaur et al
technologies In addition recent trends are directed towardimprovements in processing as well as development ofnovel release functionality The following section providesa review to some of these areas
PROCESS MODELLING SYSTEMS ANDTHEIR APPLICATIONSFilm coating process comprises various steps which canbe direct or indirect Direct parameters include air pres-sure and flow temperature of coating spray and tabletcore and spray rate The indirect parameters take accountof droplet size distribution and viscosity coating unifor-mity and thickness So different modelling systems havebeen proposed eg Digital video imaging Discrete ele-ment methodologies (DEM) Computational fluid dynam-ics (CFD)Discrete element method embodies different techniques
implying on a large number of small particles to figure outthe movement and their interaction In film coating pro-cedure DEM is used for estimating movement of tabletsand predicting the coating uniformity Computational fluiddynamics applies the principles of fluid mechanics for filmcoating process (Felton and Porter 2013 Felton 2007)The major application of process analytical technique is
that it is amenable to automation So it can be applied formonitoring and controlling various unit operations It canbe applied for product moisture content amount of coatingapplied endpoint of the process and properties of coatingeg porosity and densityHowever adaptation of PAT for coating process requires
positioning of sensors in unsuitable conditions whichcan have a bearing on sensor sensitivity So varioussophisticated analytical processes eg terahertz refractiveindex (TRI) and pulse imaging (TPI) near-infrared andraman spectroscopy (NIR) laser-induced breakdown spec-troscopy (LIBS) and confocal laser techniques can beapplied offline All of these techniques can also be usedonline since these are non-destructive except LIBSNIR methods can be employed for determining the coat-
ing amount to predict drug release rate in combinationwith multivariate analysis NIR spectroscopy can be usedto estimate an API in a coated tablet with plusmn 4 targetvalue in comparison to HPLC Major advantage of NIRspectroscopy is its non-invasiveness and rapidity Howeverit cannot be used with drugs in hydrate form Raman spec-troscopy is less sensitive to hydrates TPI technique can beused to determine the amount of coating in a side-ventedpan (Felton 2007 Felton and Porter 2013)
CONCLUSIONBased on the facts regarding film coating process we canemphasize that various recent trends may drive the indus-try closer to large scale adoption of dry powder coatingtechnologies for oral delivery First the current changes
in global austerity have pushed many pharmaceutical andbiotechnology companies to seriously examine manufac-turing costs The lower cost associated with dry powdercoating technology makes it attractive for both brand andgeneric companies seeking to reduce operating expensesAnother major driver in the future will be the needs of
advanced drug products specifically focused in the area ofcounterfeit resistance and amorphous formulation supportCounterfeit drugs are a major problem facing global phar-maceutical companies with steps being taken to protectthe supply chain and also develop visually differentiatedproducts Dry powder coating particularly electrostatic drypowder coating can be used to prepare novel identificationmarks onto drug products in a rapid cost effective mannerleading to enhanced brand identificationBeyond this the potential to eliminate the need for sol-
vents allows for more effective application of coatings tomoisture sensitive products This opens up unique oppor-tunities in the drug product design of amorphous systemsand may potentially play a role in future product designsGiven the potential of the technology academic researchwill continue in earnest as the pharmaceutical industrycontinues the adoption of the technology Over time anddriven by a number of different factors dry powder coatingappears poised to become a major pharmaceutical coatingtechnology in the future
Acknowledgment The authors wish to express thegratitude towards administrative authorities at ITSParamedical (Pharmacy) College Muradnagar Ghaziabadfor providing necessary support during collection of data
REFERENCESAulton M (ed) (1995) Mechanical properties of film coats Tay-lorampFrancis London
Bodmeier R and Paeratakul O (1994) Mechanical properties of dry andwet cellulosic and acrylic films prepared from aqueous colloidal polymerdispersions used in the coating of solid dosage forms PharmaceuticalResearch 11 882ndash88
Chen W Chang S-Y Kiang S Early W Paruchuri S and DesaiD (2008) The measurement of spray quality for pan coating processJ Pharm Innov 3 3ndash14
Chen W Chang S Y Kiang S Marchut A Lynberg O Wang JRao V Desai D Stamato H and Early W (2010) Modeling of pancoating process Prediction of tablet content uniformity and determinationof critical process parameters J Pharm Sci 99 3213ndash24
Cole G (1998) Pharmaceutical Coating Technology Taylor and FrancisLondon
Dillon R E Matheson L A and Bradford E B (1951) Sintering ofsynthetic latex particles Journal of Colloid Science 6 108ndash17
Felton L A (2007) Characterization of coating systems AAPS PharmSci Tech 8 112
Felton L A and Porter S C (2013) An update on pharmaceutical filmcoating for drug delivery Expert Opinion on Drug Delivery 10 421ndash35
Franz R and Doonan G (1983) Measuring the surface temperature oftablet beds using infrared thermometry Pharm Technol 7 55ndash67
66 J Pharm Sci Pharmacol 1 57ndash67 2014
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
Harris M R and Sellassie G (eds) (1997) Aqueous Polymeric Coat-ing for Modified Release Oral Dosage forms Marcel Dekker Inc NeyYork
Hogan J (1998) Pharmaceutical Coating Technology Taylor and FrancisLtd London
Lachman L Lieberman H A and Joseph L K (1989) The Theoryand Practice of Industrial Pharmacy vol 3 Varghese Publishing HouseMumbai
Lehmann K (ed) (1994) Coating of multiparticulates using polymericsolutions Formulation and process considerations Marcel Dekker IncNew York
Libermen H and Lachman L (2003) Pharmaceutical Dosage FormsTablets Marcel Dekker Inc NY Vols 1ndash3
Lipper R D Desai D and Kiang S (September 11ndash12 2006) CaseStudy Implementation of Design Space Concepts in Development of anActive-Coated Tablet In Real World Applications of PAT and QbD inDrug Process Development and Approval Bristol-Myers Squibb Pharma-ceutical Research Institute Arlington Virginia USA
Lippold B C and Monells P P (2001) Film formation reproducibilityof production and curing with respect to release stability of functionalcoatings from aqueous polymer dispersions Pharmazie 56 5ndash17
Malm C J and Waring C E (1937) Cellulose esters containing dicar-boxylic acid groups and process of making the same
Mazer T B Meyer G A Hwang S M Candler E L Drayer LR and Daab-Krzykowski A (1992) System for delivering an activesubstance for sustained release
Narang A K M Castoro J Varia S and Desai D (2011) Effect ofPro- and Anti-Oxidants on the Formation of Formyl Species in PVA- andPEG-Based Tablet Coating Material AAPS Washington D C USA
Narang A S Desai D and Badawy S (2012) Impact of excipientinteractions on solid dosage form stability Pharm Res 29 2660ndash83
Ogaji I and Nnoli O (2010) Film coating potential of okra gum usingparacetamol tablets as a model drug Asian J Pharm 4 130ndash34
Ogaji I J and Hoag S W (2011) Effect of grewia gum as a suspend-ing agent on ibuprofen pediatric formulation AAPS PharmSciTech 12507ndash13
Ogaji I J Okafor I S and Hoag S W (2013) Grewia gum as a poten-tial aqueous film coating agent I Some physicochemical characteristicsof fractions of grewia gum J Pharm Bioall Sci 5 53ndash60
Okutgen E Jordan M Hogan J E and Aulton M E (1991) Effectsof tablet core dimensional instability on the generation of internal stresses
within film coats part II Temperature and relative humidity variationwithin a tablet bed during aqueous film coating in an accela-cota DrugDevelopment and Industrial Pharmacy 17 1191ndash99
Opadryreg Complete Film Coating System Coating ParametersndashAqueous Formulas Colorcon Inc North America BPSI HoldingsLLC
Porter C (1990) Coating of Pharmaceutical Solid Dosage Forms MackPublishing Company Easton Pennsylvania
Porter S C (ed) (2011) Scale-Up of Film Coating Informa HealthcareNew York
Porter S C and Felton L A (2010) Techniques to assess film coat-ings and evaluate film-coated products Drug Development and IndustrialPharmacy 36 128ndash42
Rekhi G S Porter S C and Jambhekar S S (1995) Factors affectingthe release of propranolol hydrochloride from beads coated with aque-ous polymeric dispresions Drug Development and Industrial Pharmacy21 709ndash29
Sadeghi F Ford J L Rubinstein M and Rajabi-Siahboomi A R(2001) Study of drug release from pellets coated with surelease con-taining hydroxypropyl methylcellulose Drug Development and IndustrialPharmacy 27 419ndash30
Savage G V and Rhodes C T (1995) The sustained release coating ofsolid dosage forms A historical review Drug Development and Indus-trial Pharmacy 21 93ndash118
Seitz J A Swarbrick J and Boylan J C (1988) Aqueous film coat-ing Encyclopedia of Pharmaceutical Technology Marcel Dekker NewYork pp 337ndash49
Singh P Solanky T K Mudryya R Pfefferc R and Davea R (2001)Estimation of coating time in the magnetically assisted impaction coatingprocess Powder Technology 121 159ndash67
Syloidreg FP silica excipientsmdashmore than just Silica (Belgium Fred Mon-suur Grace Davison Discovery Sciences) (13 September 2010)
Systems GNP (2012) SUPERCELLtrade Tablet Coating Technology (SCT)Niro Inc 9165 Rumsey Road Columbia MD 21045 USA
Wu C and McGinity J W (2001) Influence of Ibuprofen as a solid-state plasticizer in Eudragit RS 30D on the physicochemical propertiesof coated beads AAPS PharmSciTech 2 1ndash9
Zheng W and McGinity J W (2003) Influence of Eudragit NE 30 Dblended with Eudragit L 30 D-55 on the release of phenylpropanolaminehydrochloride from coated pellets Drug Development and IndustrialPharmacy 29 357ndash66
J Pharm Sci Pharmacol 1 57ndash67 2014 67
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Film Coating Technology Past Present and Future Gaur et al
and Waring 1937 Sadeghi et al 2001 Ogaji and Nnoli2010 Ogaji and Hoag 2011 Ogaji et al 2013)
PlasticizersPlasticizers are relatively low molecular weight materialswhich are used as additives in pharmaceutical coating for-mulations to reduce the brittleness and increase the flex-ibility of the resulting film They act by weakening intermolecular attraction between polymer chains and facili-tating coalescence of discrete polymer spheres of aque-ous dispersed systems during film formation Adhesive andmechanical properties of the coating and subsequent drugrelease are dependent on the concentration of plasticizersto a great extent Plasticizers are non volatile componentsand therefore are responsible for the weight gain of dosageforms during coating A plasticizer has to be miscible andfulfil all the compatibility parameters with the polymerbeing usedAn important consideration is the content of plasticizer
as it can affect the glass transition temperature (Tg) soit should be experimentally determined by evaluating thechanges in Tg of polymer as the plasticizer content isincreased Tg is the temperature for amorphous polymersat which the behaviour of the film changes from hard andbrittle to soft and elastic An effective plasticizing agentis one which exhibits a greater decrease in the Tg of thefilm Changes in the mechanical properties of the poly-meric film are an indication of plasticizer efficacy (Seitzet al 1988 Wu and McGinity 2001)Plasticizers are classified into three groups
Anti-AdherentsAnti-adherents are used as additives to avoid agglomera-tion of the substrates during both the coating process andon subsequent storage One of the most common anti-adherents used in pharmaceutical coatings is talc but sinceit has to be used at high concentration it creates pro-cessing challenges including clogging of the spray noz-zle during coating and particle sedimentation It tends todecrease water vapour permeability and also the dissolu-tion rate of drugs due to its hydrophobic nature It alsoaffects the mechanical and adhesive properties of polymerfilms so now Glyceryl monostearate has been found as analternative to talc
Opacifying AgentsColorantsPigments deliver elegance and stability enhancement tothe solid dosage form Water-insoluble lakes and the iron
oxides are most commonly used pigments Colour migra-tion and stability issues have diminished the use of thewater-soluble dyes in film coating Pigments can signifi-cantly affect the mechanical and permeability properties ofthe film An inverse relation-ship between film-tablet adhe-sion and the particle size of the pigment has been reportedStudies have shown that the shape of the pigment par-ticle and the extent of polymer-particle interaction influ-ence the elastic modulus of polymeric films and surfacepolarity of pigments influences drug release In additionchemical incompatibilities between the pigment and thepolymer have also been reported predominantly relatedto the size and surface charge of the components andthe pH of the medium One important concept relevantto pigments is the critical pigment volume concentration(CPVC) this is the maximum concentration (based on vol-ume) of the insoluble material that can be incorporated intoa film without compromising film properties If the CPVCis exceeded insufficient polymer is present to surroundall the insoluble particles resulting in marked changes indifferent properties of the film Colorants are mainly clas-sified in to three types(i) Organic dyes and their lakes eg Erythrosine tar-trazine Sunset yellow(ii) Inorganic colours eg Iron oxide yellow red andblack titanium dioxide talc(iii) Natural colours eg Riboflavin Anthocyanins andCarmine
SolventsVehiclesThe key function of a solvent system is to dissolve ordisperse the polymers and other additivesThe major classes of solvents being used are aqueous
(Water) and Nonaqueous (Alcohols Ketones Esters Chlo-rinated hydrocarbons) Because of environmental and eco-nomic concerns water is the most commonly used solvent
Miscellaneous Coating Solution ComponentsSolid dosage form may be incorporated with several spe-cial materials such asFlavours and sweeteners are added to mask unpleasant
odours or to develop the taste eg fruit spirits (organicsolvent) aspartame water soluble pineapple flavourSurfactants are ancillary to stabilize immiscible or insol-
uble ingredients in the coating They facilitate substratewettability and promote coalescence of polymeric materialover the substratersquos surface eg Spans Tweens etcAntioxidants are incorporated to stabilize a dye system
to oxidation and colour change eg oximes phenols etcAntimicrobials are added to inhibit microbial growth
in the coating composition Various cellulosic materialsare mainly prone to microbial growth and they can notbe stored in solution form eg Carbamates alkylisothia-zloinone benzothiazoles etc
64 J Pharm Sci Pharmacol 1 57ndash67 2014
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
CURRENT TRENDS IN FILM COATING ANDFUTURE DIRECTIONSOpadry formulations provided numerous advantages ver-sus the use of individual raw materials including thereduction of the number of raw materials for Qualitycontrol testing reduced preparation time reliable colour-matched formulations tremendous appearance and excel-lent mechanical parameters However opadry dispersionsolids must be stored as 10ndash15 ww aqueous solution toattain workable 300ndash600 centipoises viscosityOpadry II category consisting HPMC and polysaccha-
rides was introduced to increase productivity The mostsignificant recent advances in the development of fully for-mulated aqueous film coatings have been the introductionof new film coatings based on polyvinyl alcohol (PVA)and sodium carboxymethylcellulose (NaCMC) PVA-basedfilms are known to have relatively low permeability formoisture vapour and oxygen whereas NaCMC-based coat-ings are glossy and have low oxygen permeability andrelatively high permeability for water vapourOpadry aqueous moisture barrier (AMB) and Opadry II
85 series are two proprietary families of PVA-based prod-ucts that were commercialized in the mid to-late 1990sThe Opadry AMB formulation were optimized to providethe lowest moisture vapour transmission rate Opadry II85 products give moisture vapour transmission rate almostas low as Opadry AMB but can be applied at significantlyhigher spray ratesFilm coatings based on PVA and NaCMC offer various
advantages Now moisture-sensitive drugs can be coatedin an aqueous coating process by PVA-based coatingsNaCMC based coatings provide demonstrable oxygenbarrier properties and excellent aesthetic characteristics(Porter and Felton 2010)
Supercelltrade Coating TechnologyThe ldquostandardrdquo practice of tablet coating often delivers anon-homogenous product Because the tablets are loadedin large rotating pans and vented for hot air drying edgesof tablets can get grounded off and intagliation can getfilled in by coating material leading to uneven coating onedgescorners and tablet faces This inaccuracy limits theuse of modified release coatings In a laboratory it is nec-essary to coat several kilograms of tablets at one timemaking RampD of a tablet dosage form costly and difficultFurther extremely hygroscopic as well as flat or other
oddly shaped tablets cannot be coated using present tech-nology so SCT (Niro Pharma Systems) technology uses asmall modular design that accurately deposits controlledamounts of coating materials on friable and extremelyhygroscopic tablets SCTrsquos continuous small-batch capablecoating process is predictable and efficient In SCT thetablets are coated in batches ranging from 30 to 120 gramswhich linearly scale up to production capacity In this tech-nique the tablets are covered with the polymer spray in
the same direction as the hot air resulting in an efficientprocess Due to SCTrsquos unique air distribution plate designthe tablets move very quickly and predictably through thespray zone receiving only a small amount of coating perpass and therefore achieving higher coating accuracy Theprocess time is short in seconds or in minutes as opposedto hours and therefore gentler on the tablets (Systems2012)Supercelltrade Coating Technology may also be used for
coating of flat or highly oblong tablets or friable tabletsIn this process drying is very fast making it possible tocoat extremely hygroscopic tablets The deposition accu-racy is sufficiently high to layer API onto tablets and uni-form layers of taste masking or modified release coatingscan be applied consecutively within a single continuousbatchUnique features of super cell coating technology are
(1) Continuous coating(2) Short processing time(3) Flexible modular design(4) No scale-up to parameters(5) Batch size for RampD (Minimum size sim30 grams)(6) Enhancing technology(7) Multi-layer coating(8) Low humidity process suitable for moisture sensitivematerials
Syloidreg FP Silicas inPharmaceutical Film CoatingsRecently film coatings have also shown encouragingresults to enable the oral delivery of peptide therapeuticsSyloidreg FP silicas have been used as excipients in manypharmaceutical formulations due to their unique morphol-ogy The combined adsorption capacity porosity particlesize and greater surface area allow them to provide severalbenefits simultaneously which can expedite manufacturingand improve efficacy of the final dosage form Syloidreg FPsilica can be used in polymeric coating systems in combi-nation of vinylcellulose or acrylic polymers (13 Septem-ber 2010)In standard concentrationsmdashAddition of Syloidreg 244FP
silica to film coating provides following advantages-Improved spray propertiesElimination of the need for talcImprovement of suspension propertiesPrevention of valve cloggingMinimal settling in spray linesSmoothen tablet surfaceReduction of adhesionApplications Anti-tacking agent Oral peptide deliveryODT formulations Enteric coatings Sustained releasecoatings Controlled release coatings (Grace Discovery)In recent years there has been a growing focus on
conducting fundamental studies through the applicationof appropriate modelling techniques and novel analytical
J Pharm Sci Pharmacol 1 57ndash67 2014 65
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Film Coating Technology Past Present and Future Gaur et al
technologies In addition recent trends are directed towardimprovements in processing as well as development ofnovel release functionality The following section providesa review to some of these areas
PROCESS MODELLING SYSTEMS ANDTHEIR APPLICATIONSFilm coating process comprises various steps which canbe direct or indirect Direct parameters include air pres-sure and flow temperature of coating spray and tabletcore and spray rate The indirect parameters take accountof droplet size distribution and viscosity coating unifor-mity and thickness So different modelling systems havebeen proposed eg Digital video imaging Discrete ele-ment methodologies (DEM) Computational fluid dynam-ics (CFD)Discrete element method embodies different techniques
implying on a large number of small particles to figure outthe movement and their interaction In film coating pro-cedure DEM is used for estimating movement of tabletsand predicting the coating uniformity Computational fluiddynamics applies the principles of fluid mechanics for filmcoating process (Felton and Porter 2013 Felton 2007)The major application of process analytical technique is
that it is amenable to automation So it can be applied formonitoring and controlling various unit operations It canbe applied for product moisture content amount of coatingapplied endpoint of the process and properties of coatingeg porosity and densityHowever adaptation of PAT for coating process requires
positioning of sensors in unsuitable conditions whichcan have a bearing on sensor sensitivity So varioussophisticated analytical processes eg terahertz refractiveindex (TRI) and pulse imaging (TPI) near-infrared andraman spectroscopy (NIR) laser-induced breakdown spec-troscopy (LIBS) and confocal laser techniques can beapplied offline All of these techniques can also be usedonline since these are non-destructive except LIBSNIR methods can be employed for determining the coat-
ing amount to predict drug release rate in combinationwith multivariate analysis NIR spectroscopy can be usedto estimate an API in a coated tablet with plusmn 4 targetvalue in comparison to HPLC Major advantage of NIRspectroscopy is its non-invasiveness and rapidity Howeverit cannot be used with drugs in hydrate form Raman spec-troscopy is less sensitive to hydrates TPI technique can beused to determine the amount of coating in a side-ventedpan (Felton 2007 Felton and Porter 2013)
CONCLUSIONBased on the facts regarding film coating process we canemphasize that various recent trends may drive the indus-try closer to large scale adoption of dry powder coatingtechnologies for oral delivery First the current changes
in global austerity have pushed many pharmaceutical andbiotechnology companies to seriously examine manufac-turing costs The lower cost associated with dry powdercoating technology makes it attractive for both brand andgeneric companies seeking to reduce operating expensesAnother major driver in the future will be the needs of
advanced drug products specifically focused in the area ofcounterfeit resistance and amorphous formulation supportCounterfeit drugs are a major problem facing global phar-maceutical companies with steps being taken to protectthe supply chain and also develop visually differentiatedproducts Dry powder coating particularly electrostatic drypowder coating can be used to prepare novel identificationmarks onto drug products in a rapid cost effective mannerleading to enhanced brand identificationBeyond this the potential to eliminate the need for sol-
vents allows for more effective application of coatings tomoisture sensitive products This opens up unique oppor-tunities in the drug product design of amorphous systemsand may potentially play a role in future product designsGiven the potential of the technology academic researchwill continue in earnest as the pharmaceutical industrycontinues the adoption of the technology Over time anddriven by a number of different factors dry powder coatingappears poised to become a major pharmaceutical coatingtechnology in the future
Acknowledgment The authors wish to express thegratitude towards administrative authorities at ITSParamedical (Pharmacy) College Muradnagar Ghaziabadfor providing necessary support during collection of data
REFERENCESAulton M (ed) (1995) Mechanical properties of film coats Tay-lorampFrancis London
Bodmeier R and Paeratakul O (1994) Mechanical properties of dry andwet cellulosic and acrylic films prepared from aqueous colloidal polymerdispersions used in the coating of solid dosage forms PharmaceuticalResearch 11 882ndash88
Chen W Chang S-Y Kiang S Early W Paruchuri S and DesaiD (2008) The measurement of spray quality for pan coating processJ Pharm Innov 3 3ndash14
Chen W Chang S Y Kiang S Marchut A Lynberg O Wang JRao V Desai D Stamato H and Early W (2010) Modeling of pancoating process Prediction of tablet content uniformity and determinationof critical process parameters J Pharm Sci 99 3213ndash24
Cole G (1998) Pharmaceutical Coating Technology Taylor and FrancisLondon
Dillon R E Matheson L A and Bradford E B (1951) Sintering ofsynthetic latex particles Journal of Colloid Science 6 108ndash17
Felton L A (2007) Characterization of coating systems AAPS PharmSci Tech 8 112
Felton L A and Porter S C (2013) An update on pharmaceutical filmcoating for drug delivery Expert Opinion on Drug Delivery 10 421ndash35
Franz R and Doonan G (1983) Measuring the surface temperature oftablet beds using infrared thermometry Pharm Technol 7 55ndash67
66 J Pharm Sci Pharmacol 1 57ndash67 2014
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
Harris M R and Sellassie G (eds) (1997) Aqueous Polymeric Coat-ing for Modified Release Oral Dosage forms Marcel Dekker Inc NeyYork
Hogan J (1998) Pharmaceutical Coating Technology Taylor and FrancisLtd London
Lachman L Lieberman H A and Joseph L K (1989) The Theoryand Practice of Industrial Pharmacy vol 3 Varghese Publishing HouseMumbai
Lehmann K (ed) (1994) Coating of multiparticulates using polymericsolutions Formulation and process considerations Marcel Dekker IncNew York
Libermen H and Lachman L (2003) Pharmaceutical Dosage FormsTablets Marcel Dekker Inc NY Vols 1ndash3
Lipper R D Desai D and Kiang S (September 11ndash12 2006) CaseStudy Implementation of Design Space Concepts in Development of anActive-Coated Tablet In Real World Applications of PAT and QbD inDrug Process Development and Approval Bristol-Myers Squibb Pharma-ceutical Research Institute Arlington Virginia USA
Lippold B C and Monells P P (2001) Film formation reproducibilityof production and curing with respect to release stability of functionalcoatings from aqueous polymer dispersions Pharmazie 56 5ndash17
Malm C J and Waring C E (1937) Cellulose esters containing dicar-boxylic acid groups and process of making the same
Mazer T B Meyer G A Hwang S M Candler E L Drayer LR and Daab-Krzykowski A (1992) System for delivering an activesubstance for sustained release
Narang A K M Castoro J Varia S and Desai D (2011) Effect ofPro- and Anti-Oxidants on the Formation of Formyl Species in PVA- andPEG-Based Tablet Coating Material AAPS Washington D C USA
Narang A S Desai D and Badawy S (2012) Impact of excipientinteractions on solid dosage form stability Pharm Res 29 2660ndash83
Ogaji I and Nnoli O (2010) Film coating potential of okra gum usingparacetamol tablets as a model drug Asian J Pharm 4 130ndash34
Ogaji I J and Hoag S W (2011) Effect of grewia gum as a suspend-ing agent on ibuprofen pediatric formulation AAPS PharmSciTech 12507ndash13
Ogaji I J Okafor I S and Hoag S W (2013) Grewia gum as a poten-tial aqueous film coating agent I Some physicochemical characteristicsof fractions of grewia gum J Pharm Bioall Sci 5 53ndash60
Okutgen E Jordan M Hogan J E and Aulton M E (1991) Effectsof tablet core dimensional instability on the generation of internal stresses
within film coats part II Temperature and relative humidity variationwithin a tablet bed during aqueous film coating in an accela-cota DrugDevelopment and Industrial Pharmacy 17 1191ndash99
Opadryreg Complete Film Coating System Coating ParametersndashAqueous Formulas Colorcon Inc North America BPSI HoldingsLLC
Porter C (1990) Coating of Pharmaceutical Solid Dosage Forms MackPublishing Company Easton Pennsylvania
Porter S C (ed) (2011) Scale-Up of Film Coating Informa HealthcareNew York
Porter S C and Felton L A (2010) Techniques to assess film coat-ings and evaluate film-coated products Drug Development and IndustrialPharmacy 36 128ndash42
Rekhi G S Porter S C and Jambhekar S S (1995) Factors affectingthe release of propranolol hydrochloride from beads coated with aque-ous polymeric dispresions Drug Development and Industrial Pharmacy21 709ndash29
Sadeghi F Ford J L Rubinstein M and Rajabi-Siahboomi A R(2001) Study of drug release from pellets coated with surelease con-taining hydroxypropyl methylcellulose Drug Development and IndustrialPharmacy 27 419ndash30
Savage G V and Rhodes C T (1995) The sustained release coating ofsolid dosage forms A historical review Drug Development and Indus-trial Pharmacy 21 93ndash118
Seitz J A Swarbrick J and Boylan J C (1988) Aqueous film coat-ing Encyclopedia of Pharmaceutical Technology Marcel Dekker NewYork pp 337ndash49
Singh P Solanky T K Mudryya R Pfefferc R and Davea R (2001)Estimation of coating time in the magnetically assisted impaction coatingprocess Powder Technology 121 159ndash67
Syloidreg FP silica excipientsmdashmore than just Silica (Belgium Fred Mon-suur Grace Davison Discovery Sciences) (13 September 2010)
Systems GNP (2012) SUPERCELLtrade Tablet Coating Technology (SCT)Niro Inc 9165 Rumsey Road Columbia MD 21045 USA
Wu C and McGinity J W (2001) Influence of Ibuprofen as a solid-state plasticizer in Eudragit RS 30D on the physicochemical propertiesof coated beads AAPS PharmSciTech 2 1ndash9
Zheng W and McGinity J W (2003) Influence of Eudragit NE 30 Dblended with Eudragit L 30 D-55 on the release of phenylpropanolaminehydrochloride from coated pellets Drug Development and IndustrialPharmacy 29 357ndash66
J Pharm Sci Pharmacol 1 57ndash67 2014 67
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
CURRENT TRENDS IN FILM COATING ANDFUTURE DIRECTIONSOpadry formulations provided numerous advantages ver-sus the use of individual raw materials including thereduction of the number of raw materials for Qualitycontrol testing reduced preparation time reliable colour-matched formulations tremendous appearance and excel-lent mechanical parameters However opadry dispersionsolids must be stored as 10ndash15 ww aqueous solution toattain workable 300ndash600 centipoises viscosityOpadry II category consisting HPMC and polysaccha-
rides was introduced to increase productivity The mostsignificant recent advances in the development of fully for-mulated aqueous film coatings have been the introductionof new film coatings based on polyvinyl alcohol (PVA)and sodium carboxymethylcellulose (NaCMC) PVA-basedfilms are known to have relatively low permeability formoisture vapour and oxygen whereas NaCMC-based coat-ings are glossy and have low oxygen permeability andrelatively high permeability for water vapourOpadry aqueous moisture barrier (AMB) and Opadry II
85 series are two proprietary families of PVA-based prod-ucts that were commercialized in the mid to-late 1990sThe Opadry AMB formulation were optimized to providethe lowest moisture vapour transmission rate Opadry II85 products give moisture vapour transmission rate almostas low as Opadry AMB but can be applied at significantlyhigher spray ratesFilm coatings based on PVA and NaCMC offer various
advantages Now moisture-sensitive drugs can be coatedin an aqueous coating process by PVA-based coatingsNaCMC based coatings provide demonstrable oxygenbarrier properties and excellent aesthetic characteristics(Porter and Felton 2010)
Supercelltrade Coating TechnologyThe ldquostandardrdquo practice of tablet coating often delivers anon-homogenous product Because the tablets are loadedin large rotating pans and vented for hot air drying edgesof tablets can get grounded off and intagliation can getfilled in by coating material leading to uneven coating onedgescorners and tablet faces This inaccuracy limits theuse of modified release coatings In a laboratory it is nec-essary to coat several kilograms of tablets at one timemaking RampD of a tablet dosage form costly and difficultFurther extremely hygroscopic as well as flat or other
oddly shaped tablets cannot be coated using present tech-nology so SCT (Niro Pharma Systems) technology uses asmall modular design that accurately deposits controlledamounts of coating materials on friable and extremelyhygroscopic tablets SCTrsquos continuous small-batch capablecoating process is predictable and efficient In SCT thetablets are coated in batches ranging from 30 to 120 gramswhich linearly scale up to production capacity In this tech-nique the tablets are covered with the polymer spray in
the same direction as the hot air resulting in an efficientprocess Due to SCTrsquos unique air distribution plate designthe tablets move very quickly and predictably through thespray zone receiving only a small amount of coating perpass and therefore achieving higher coating accuracy Theprocess time is short in seconds or in minutes as opposedto hours and therefore gentler on the tablets (Systems2012)Supercelltrade Coating Technology may also be used for
coating of flat or highly oblong tablets or friable tabletsIn this process drying is very fast making it possible tocoat extremely hygroscopic tablets The deposition accu-racy is sufficiently high to layer API onto tablets and uni-form layers of taste masking or modified release coatingscan be applied consecutively within a single continuousbatchUnique features of super cell coating technology are
(1) Continuous coating(2) Short processing time(3) Flexible modular design(4) No scale-up to parameters(5) Batch size for RampD (Minimum size sim30 grams)(6) Enhancing technology(7) Multi-layer coating(8) Low humidity process suitable for moisture sensitivematerials
Syloidreg FP Silicas inPharmaceutical Film CoatingsRecently film coatings have also shown encouragingresults to enable the oral delivery of peptide therapeuticsSyloidreg FP silicas have been used as excipients in manypharmaceutical formulations due to their unique morphol-ogy The combined adsorption capacity porosity particlesize and greater surface area allow them to provide severalbenefits simultaneously which can expedite manufacturingand improve efficacy of the final dosage form Syloidreg FPsilica can be used in polymeric coating systems in combi-nation of vinylcellulose or acrylic polymers (13 Septem-ber 2010)In standard concentrationsmdashAddition of Syloidreg 244FP
silica to film coating provides following advantages-Improved spray propertiesElimination of the need for talcImprovement of suspension propertiesPrevention of valve cloggingMinimal settling in spray linesSmoothen tablet surfaceReduction of adhesionApplications Anti-tacking agent Oral peptide deliveryODT formulations Enteric coatings Sustained releasecoatings Controlled release coatings (Grace Discovery)In recent years there has been a growing focus on
conducting fundamental studies through the applicationof appropriate modelling techniques and novel analytical
J Pharm Sci Pharmacol 1 57ndash67 2014 65
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Film Coating Technology Past Present and Future Gaur et al
technologies In addition recent trends are directed towardimprovements in processing as well as development ofnovel release functionality The following section providesa review to some of these areas
PROCESS MODELLING SYSTEMS ANDTHEIR APPLICATIONSFilm coating process comprises various steps which canbe direct or indirect Direct parameters include air pres-sure and flow temperature of coating spray and tabletcore and spray rate The indirect parameters take accountof droplet size distribution and viscosity coating unifor-mity and thickness So different modelling systems havebeen proposed eg Digital video imaging Discrete ele-ment methodologies (DEM) Computational fluid dynam-ics (CFD)Discrete element method embodies different techniques
implying on a large number of small particles to figure outthe movement and their interaction In film coating pro-cedure DEM is used for estimating movement of tabletsand predicting the coating uniformity Computational fluiddynamics applies the principles of fluid mechanics for filmcoating process (Felton and Porter 2013 Felton 2007)The major application of process analytical technique is
that it is amenable to automation So it can be applied formonitoring and controlling various unit operations It canbe applied for product moisture content amount of coatingapplied endpoint of the process and properties of coatingeg porosity and densityHowever adaptation of PAT for coating process requires
positioning of sensors in unsuitable conditions whichcan have a bearing on sensor sensitivity So varioussophisticated analytical processes eg terahertz refractiveindex (TRI) and pulse imaging (TPI) near-infrared andraman spectroscopy (NIR) laser-induced breakdown spec-troscopy (LIBS) and confocal laser techniques can beapplied offline All of these techniques can also be usedonline since these are non-destructive except LIBSNIR methods can be employed for determining the coat-
ing amount to predict drug release rate in combinationwith multivariate analysis NIR spectroscopy can be usedto estimate an API in a coated tablet with plusmn 4 targetvalue in comparison to HPLC Major advantage of NIRspectroscopy is its non-invasiveness and rapidity Howeverit cannot be used with drugs in hydrate form Raman spec-troscopy is less sensitive to hydrates TPI technique can beused to determine the amount of coating in a side-ventedpan (Felton 2007 Felton and Porter 2013)
CONCLUSIONBased on the facts regarding film coating process we canemphasize that various recent trends may drive the indus-try closer to large scale adoption of dry powder coatingtechnologies for oral delivery First the current changes
in global austerity have pushed many pharmaceutical andbiotechnology companies to seriously examine manufac-turing costs The lower cost associated with dry powdercoating technology makes it attractive for both brand andgeneric companies seeking to reduce operating expensesAnother major driver in the future will be the needs of
advanced drug products specifically focused in the area ofcounterfeit resistance and amorphous formulation supportCounterfeit drugs are a major problem facing global phar-maceutical companies with steps being taken to protectthe supply chain and also develop visually differentiatedproducts Dry powder coating particularly electrostatic drypowder coating can be used to prepare novel identificationmarks onto drug products in a rapid cost effective mannerleading to enhanced brand identificationBeyond this the potential to eliminate the need for sol-
vents allows for more effective application of coatings tomoisture sensitive products This opens up unique oppor-tunities in the drug product design of amorphous systemsand may potentially play a role in future product designsGiven the potential of the technology academic researchwill continue in earnest as the pharmaceutical industrycontinues the adoption of the technology Over time anddriven by a number of different factors dry powder coatingappears poised to become a major pharmaceutical coatingtechnology in the future
Acknowledgment The authors wish to express thegratitude towards administrative authorities at ITSParamedical (Pharmacy) College Muradnagar Ghaziabadfor providing necessary support during collection of data
REFERENCESAulton M (ed) (1995) Mechanical properties of film coats Tay-lorampFrancis London
Bodmeier R and Paeratakul O (1994) Mechanical properties of dry andwet cellulosic and acrylic films prepared from aqueous colloidal polymerdispersions used in the coating of solid dosage forms PharmaceuticalResearch 11 882ndash88
Chen W Chang S-Y Kiang S Early W Paruchuri S and DesaiD (2008) The measurement of spray quality for pan coating processJ Pharm Innov 3 3ndash14
Chen W Chang S Y Kiang S Marchut A Lynberg O Wang JRao V Desai D Stamato H and Early W (2010) Modeling of pancoating process Prediction of tablet content uniformity and determinationof critical process parameters J Pharm Sci 99 3213ndash24
Cole G (1998) Pharmaceutical Coating Technology Taylor and FrancisLondon
Dillon R E Matheson L A and Bradford E B (1951) Sintering ofsynthetic latex particles Journal of Colloid Science 6 108ndash17
Felton L A (2007) Characterization of coating systems AAPS PharmSci Tech 8 112
Felton L A and Porter S C (2013) An update on pharmaceutical filmcoating for drug delivery Expert Opinion on Drug Delivery 10 421ndash35
Franz R and Doonan G (1983) Measuring the surface temperature oftablet beds using infrared thermometry Pharm Technol 7 55ndash67
66 J Pharm Sci Pharmacol 1 57ndash67 2014
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
Harris M R and Sellassie G (eds) (1997) Aqueous Polymeric Coat-ing for Modified Release Oral Dosage forms Marcel Dekker Inc NeyYork
Hogan J (1998) Pharmaceutical Coating Technology Taylor and FrancisLtd London
Lachman L Lieberman H A and Joseph L K (1989) The Theoryand Practice of Industrial Pharmacy vol 3 Varghese Publishing HouseMumbai
Lehmann K (ed) (1994) Coating of multiparticulates using polymericsolutions Formulation and process considerations Marcel Dekker IncNew York
Libermen H and Lachman L (2003) Pharmaceutical Dosage FormsTablets Marcel Dekker Inc NY Vols 1ndash3
Lipper R D Desai D and Kiang S (September 11ndash12 2006) CaseStudy Implementation of Design Space Concepts in Development of anActive-Coated Tablet In Real World Applications of PAT and QbD inDrug Process Development and Approval Bristol-Myers Squibb Pharma-ceutical Research Institute Arlington Virginia USA
Lippold B C and Monells P P (2001) Film formation reproducibilityof production and curing with respect to release stability of functionalcoatings from aqueous polymer dispersions Pharmazie 56 5ndash17
Malm C J and Waring C E (1937) Cellulose esters containing dicar-boxylic acid groups and process of making the same
Mazer T B Meyer G A Hwang S M Candler E L Drayer LR and Daab-Krzykowski A (1992) System for delivering an activesubstance for sustained release
Narang A K M Castoro J Varia S and Desai D (2011) Effect ofPro- and Anti-Oxidants on the Formation of Formyl Species in PVA- andPEG-Based Tablet Coating Material AAPS Washington D C USA
Narang A S Desai D and Badawy S (2012) Impact of excipientinteractions on solid dosage form stability Pharm Res 29 2660ndash83
Ogaji I and Nnoli O (2010) Film coating potential of okra gum usingparacetamol tablets as a model drug Asian J Pharm 4 130ndash34
Ogaji I J and Hoag S W (2011) Effect of grewia gum as a suspend-ing agent on ibuprofen pediatric formulation AAPS PharmSciTech 12507ndash13
Ogaji I J Okafor I S and Hoag S W (2013) Grewia gum as a poten-tial aqueous film coating agent I Some physicochemical characteristicsof fractions of grewia gum J Pharm Bioall Sci 5 53ndash60
Okutgen E Jordan M Hogan J E and Aulton M E (1991) Effectsof tablet core dimensional instability on the generation of internal stresses
within film coats part II Temperature and relative humidity variationwithin a tablet bed during aqueous film coating in an accela-cota DrugDevelopment and Industrial Pharmacy 17 1191ndash99
Opadryreg Complete Film Coating System Coating ParametersndashAqueous Formulas Colorcon Inc North America BPSI HoldingsLLC
Porter C (1990) Coating of Pharmaceutical Solid Dosage Forms MackPublishing Company Easton Pennsylvania
Porter S C (ed) (2011) Scale-Up of Film Coating Informa HealthcareNew York
Porter S C and Felton L A (2010) Techniques to assess film coat-ings and evaluate film-coated products Drug Development and IndustrialPharmacy 36 128ndash42
Rekhi G S Porter S C and Jambhekar S S (1995) Factors affectingthe release of propranolol hydrochloride from beads coated with aque-ous polymeric dispresions Drug Development and Industrial Pharmacy21 709ndash29
Sadeghi F Ford J L Rubinstein M and Rajabi-Siahboomi A R(2001) Study of drug release from pellets coated with surelease con-taining hydroxypropyl methylcellulose Drug Development and IndustrialPharmacy 27 419ndash30
Savage G V and Rhodes C T (1995) The sustained release coating ofsolid dosage forms A historical review Drug Development and Indus-trial Pharmacy 21 93ndash118
Seitz J A Swarbrick J and Boylan J C (1988) Aqueous film coat-ing Encyclopedia of Pharmaceutical Technology Marcel Dekker NewYork pp 337ndash49
Singh P Solanky T K Mudryya R Pfefferc R and Davea R (2001)Estimation of coating time in the magnetically assisted impaction coatingprocess Powder Technology 121 159ndash67
Syloidreg FP silica excipientsmdashmore than just Silica (Belgium Fred Mon-suur Grace Davison Discovery Sciences) (13 September 2010)
Systems GNP (2012) SUPERCELLtrade Tablet Coating Technology (SCT)Niro Inc 9165 Rumsey Road Columbia MD 21045 USA
Wu C and McGinity J W (2001) Influence of Ibuprofen as a solid-state plasticizer in Eudragit RS 30D on the physicochemical propertiesof coated beads AAPS PharmSciTech 2 1ndash9
Zheng W and McGinity J W (2003) Influence of Eudragit NE 30 Dblended with Eudragit L 30 D-55 on the release of phenylpropanolaminehydrochloride from coated pellets Drug Development and IndustrialPharmacy 29 357ndash66
J Pharm Sci Pharmacol 1 57ndash67 2014 67
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Film Coating Technology Past Present and Future Gaur et al
technologies In addition recent trends are directed towardimprovements in processing as well as development ofnovel release functionality The following section providesa review to some of these areas
PROCESS MODELLING SYSTEMS ANDTHEIR APPLICATIONSFilm coating process comprises various steps which canbe direct or indirect Direct parameters include air pres-sure and flow temperature of coating spray and tabletcore and spray rate The indirect parameters take accountof droplet size distribution and viscosity coating unifor-mity and thickness So different modelling systems havebeen proposed eg Digital video imaging Discrete ele-ment methodologies (DEM) Computational fluid dynam-ics (CFD)Discrete element method embodies different techniques
implying on a large number of small particles to figure outthe movement and their interaction In film coating pro-cedure DEM is used for estimating movement of tabletsand predicting the coating uniformity Computational fluiddynamics applies the principles of fluid mechanics for filmcoating process (Felton and Porter 2013 Felton 2007)The major application of process analytical technique is
that it is amenable to automation So it can be applied formonitoring and controlling various unit operations It canbe applied for product moisture content amount of coatingapplied endpoint of the process and properties of coatingeg porosity and densityHowever adaptation of PAT for coating process requires
positioning of sensors in unsuitable conditions whichcan have a bearing on sensor sensitivity So varioussophisticated analytical processes eg terahertz refractiveindex (TRI) and pulse imaging (TPI) near-infrared andraman spectroscopy (NIR) laser-induced breakdown spec-troscopy (LIBS) and confocal laser techniques can beapplied offline All of these techniques can also be usedonline since these are non-destructive except LIBSNIR methods can be employed for determining the coat-
ing amount to predict drug release rate in combinationwith multivariate analysis NIR spectroscopy can be usedto estimate an API in a coated tablet with plusmn 4 targetvalue in comparison to HPLC Major advantage of NIRspectroscopy is its non-invasiveness and rapidity Howeverit cannot be used with drugs in hydrate form Raman spec-troscopy is less sensitive to hydrates TPI technique can beused to determine the amount of coating in a side-ventedpan (Felton 2007 Felton and Porter 2013)
CONCLUSIONBased on the facts regarding film coating process we canemphasize that various recent trends may drive the indus-try closer to large scale adoption of dry powder coatingtechnologies for oral delivery First the current changes
in global austerity have pushed many pharmaceutical andbiotechnology companies to seriously examine manufac-turing costs The lower cost associated with dry powdercoating technology makes it attractive for both brand andgeneric companies seeking to reduce operating expensesAnother major driver in the future will be the needs of
advanced drug products specifically focused in the area ofcounterfeit resistance and amorphous formulation supportCounterfeit drugs are a major problem facing global phar-maceutical companies with steps being taken to protectthe supply chain and also develop visually differentiatedproducts Dry powder coating particularly electrostatic drypowder coating can be used to prepare novel identificationmarks onto drug products in a rapid cost effective mannerleading to enhanced brand identificationBeyond this the potential to eliminate the need for sol-
vents allows for more effective application of coatings tomoisture sensitive products This opens up unique oppor-tunities in the drug product design of amorphous systemsand may potentially play a role in future product designsGiven the potential of the technology academic researchwill continue in earnest as the pharmaceutical industrycontinues the adoption of the technology Over time anddriven by a number of different factors dry powder coatingappears poised to become a major pharmaceutical coatingtechnology in the future
Acknowledgment The authors wish to express thegratitude towards administrative authorities at ITSParamedical (Pharmacy) College Muradnagar Ghaziabadfor providing necessary support during collection of data
REFERENCESAulton M (ed) (1995) Mechanical properties of film coats Tay-lorampFrancis London
Bodmeier R and Paeratakul O (1994) Mechanical properties of dry andwet cellulosic and acrylic films prepared from aqueous colloidal polymerdispersions used in the coating of solid dosage forms PharmaceuticalResearch 11 882ndash88
Chen W Chang S-Y Kiang S Early W Paruchuri S and DesaiD (2008) The measurement of spray quality for pan coating processJ Pharm Innov 3 3ndash14
Chen W Chang S Y Kiang S Marchut A Lynberg O Wang JRao V Desai D Stamato H and Early W (2010) Modeling of pancoating process Prediction of tablet content uniformity and determinationof critical process parameters J Pharm Sci 99 3213ndash24
Cole G (1998) Pharmaceutical Coating Technology Taylor and FrancisLondon
Dillon R E Matheson L A and Bradford E B (1951) Sintering ofsynthetic latex particles Journal of Colloid Science 6 108ndash17
Felton L A (2007) Characterization of coating systems AAPS PharmSci Tech 8 112
Felton L A and Porter S C (2013) An update on pharmaceutical filmcoating for drug delivery Expert Opinion on Drug Delivery 10 421ndash35
Franz R and Doonan G (1983) Measuring the surface temperature oftablet beds using infrared thermometry Pharm Technol 7 55ndash67
66 J Pharm Sci Pharmacol 1 57ndash67 2014
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
Harris M R and Sellassie G (eds) (1997) Aqueous Polymeric Coat-ing for Modified Release Oral Dosage forms Marcel Dekker Inc NeyYork
Hogan J (1998) Pharmaceutical Coating Technology Taylor and FrancisLtd London
Lachman L Lieberman H A and Joseph L K (1989) The Theoryand Practice of Industrial Pharmacy vol 3 Varghese Publishing HouseMumbai
Lehmann K (ed) (1994) Coating of multiparticulates using polymericsolutions Formulation and process considerations Marcel Dekker IncNew York
Libermen H and Lachman L (2003) Pharmaceutical Dosage FormsTablets Marcel Dekker Inc NY Vols 1ndash3
Lipper R D Desai D and Kiang S (September 11ndash12 2006) CaseStudy Implementation of Design Space Concepts in Development of anActive-Coated Tablet In Real World Applications of PAT and QbD inDrug Process Development and Approval Bristol-Myers Squibb Pharma-ceutical Research Institute Arlington Virginia USA
Lippold B C and Monells P P (2001) Film formation reproducibilityof production and curing with respect to release stability of functionalcoatings from aqueous polymer dispersions Pharmazie 56 5ndash17
Malm C J and Waring C E (1937) Cellulose esters containing dicar-boxylic acid groups and process of making the same
Mazer T B Meyer G A Hwang S M Candler E L Drayer LR and Daab-Krzykowski A (1992) System for delivering an activesubstance for sustained release
Narang A K M Castoro J Varia S and Desai D (2011) Effect ofPro- and Anti-Oxidants on the Formation of Formyl Species in PVA- andPEG-Based Tablet Coating Material AAPS Washington D C USA
Narang A S Desai D and Badawy S (2012) Impact of excipientinteractions on solid dosage form stability Pharm Res 29 2660ndash83
Ogaji I and Nnoli O (2010) Film coating potential of okra gum usingparacetamol tablets as a model drug Asian J Pharm 4 130ndash34
Ogaji I J and Hoag S W (2011) Effect of grewia gum as a suspend-ing agent on ibuprofen pediatric formulation AAPS PharmSciTech 12507ndash13
Ogaji I J Okafor I S and Hoag S W (2013) Grewia gum as a poten-tial aqueous film coating agent I Some physicochemical characteristicsof fractions of grewia gum J Pharm Bioall Sci 5 53ndash60
Okutgen E Jordan M Hogan J E and Aulton M E (1991) Effectsof tablet core dimensional instability on the generation of internal stresses
within film coats part II Temperature and relative humidity variationwithin a tablet bed during aqueous film coating in an accela-cota DrugDevelopment and Industrial Pharmacy 17 1191ndash99
Opadryreg Complete Film Coating System Coating ParametersndashAqueous Formulas Colorcon Inc North America BPSI HoldingsLLC
Porter C (1990) Coating of Pharmaceutical Solid Dosage Forms MackPublishing Company Easton Pennsylvania
Porter S C (ed) (2011) Scale-Up of Film Coating Informa HealthcareNew York
Porter S C and Felton L A (2010) Techniques to assess film coat-ings and evaluate film-coated products Drug Development and IndustrialPharmacy 36 128ndash42
Rekhi G S Porter S C and Jambhekar S S (1995) Factors affectingthe release of propranolol hydrochloride from beads coated with aque-ous polymeric dispresions Drug Development and Industrial Pharmacy21 709ndash29
Sadeghi F Ford J L Rubinstein M and Rajabi-Siahboomi A R(2001) Study of drug release from pellets coated with surelease con-taining hydroxypropyl methylcellulose Drug Development and IndustrialPharmacy 27 419ndash30
Savage G V and Rhodes C T (1995) The sustained release coating ofsolid dosage forms A historical review Drug Development and Indus-trial Pharmacy 21 93ndash118
Seitz J A Swarbrick J and Boylan J C (1988) Aqueous film coat-ing Encyclopedia of Pharmaceutical Technology Marcel Dekker NewYork pp 337ndash49
Singh P Solanky T K Mudryya R Pfefferc R and Davea R (2001)Estimation of coating time in the magnetically assisted impaction coatingprocess Powder Technology 121 159ndash67
Syloidreg FP silica excipientsmdashmore than just Silica (Belgium Fred Mon-suur Grace Davison Discovery Sciences) (13 September 2010)
Systems GNP (2012) SUPERCELLtrade Tablet Coating Technology (SCT)Niro Inc 9165 Rumsey Road Columbia MD 21045 USA
Wu C and McGinity J W (2001) Influence of Ibuprofen as a solid-state plasticizer in Eudragit RS 30D on the physicochemical propertiesof coated beads AAPS PharmSciTech 2 1ndash9
Zheng W and McGinity J W (2003) Influence of Eudragit NE 30 Dblended with Eudragit L 30 D-55 on the release of phenylpropanolaminehydrochloride from coated pellets Drug Development and IndustrialPharmacy 29 357ndash66
J Pharm Sci Pharmacol 1 57ndash67 2014 67
Delivered by Publishing Technology to Guest UserIP 162218208135 On Tue 14 Oct 2014 142421
Copyright American Scientific Publishers
Gaur et al Film Coating Technology Past Present and Future
Harris M R and Sellassie G (eds) (1997) Aqueous Polymeric Coat-ing for Modified Release Oral Dosage forms Marcel Dekker Inc NeyYork
Hogan J (1998) Pharmaceutical Coating Technology Taylor and FrancisLtd London
Lachman L Lieberman H A and Joseph L K (1989) The Theoryand Practice of Industrial Pharmacy vol 3 Varghese Publishing HouseMumbai
Lehmann K (ed) (1994) Coating of multiparticulates using polymericsolutions Formulation and process considerations Marcel Dekker IncNew York
Libermen H and Lachman L (2003) Pharmaceutical Dosage FormsTablets Marcel Dekker Inc NY Vols 1ndash3
Lipper R D Desai D and Kiang S (September 11ndash12 2006) CaseStudy Implementation of Design Space Concepts in Development of anActive-Coated Tablet In Real World Applications of PAT and QbD inDrug Process Development and Approval Bristol-Myers Squibb Pharma-ceutical Research Institute Arlington Virginia USA
Lippold B C and Monells P P (2001) Film formation reproducibilityof production and curing with respect to release stability of functionalcoatings from aqueous polymer dispersions Pharmazie 56 5ndash17
Malm C J and Waring C E (1937) Cellulose esters containing dicar-boxylic acid groups and process of making the same
Mazer T B Meyer G A Hwang S M Candler E L Drayer LR and Daab-Krzykowski A (1992) System for delivering an activesubstance for sustained release
Narang A K M Castoro J Varia S and Desai D (2011) Effect ofPro- and Anti-Oxidants on the Formation of Formyl Species in PVA- andPEG-Based Tablet Coating Material AAPS Washington D C USA
Narang A S Desai D and Badawy S (2012) Impact of excipientinteractions on solid dosage form stability Pharm Res 29 2660ndash83
Ogaji I and Nnoli O (2010) Film coating potential of okra gum usingparacetamol tablets as a model drug Asian J Pharm 4 130ndash34
Ogaji I J and Hoag S W (2011) Effect of grewia gum as a suspend-ing agent on ibuprofen pediatric formulation AAPS PharmSciTech 12507ndash13
Ogaji I J Okafor I S and Hoag S W (2013) Grewia gum as a poten-tial aqueous film coating agent I Some physicochemical characteristicsof fractions of grewia gum J Pharm Bioall Sci 5 53ndash60
Okutgen E Jordan M Hogan J E and Aulton M E (1991) Effectsof tablet core dimensional instability on the generation of internal stresses
within film coats part II Temperature and relative humidity variationwithin a tablet bed during aqueous film coating in an accela-cota DrugDevelopment and Industrial Pharmacy 17 1191ndash99
Opadryreg Complete Film Coating System Coating ParametersndashAqueous Formulas Colorcon Inc North America BPSI HoldingsLLC
Porter C (1990) Coating of Pharmaceutical Solid Dosage Forms MackPublishing Company Easton Pennsylvania
Porter S C (ed) (2011) Scale-Up of Film Coating Informa HealthcareNew York
Porter S C and Felton L A (2010) Techniques to assess film coat-ings and evaluate film-coated products Drug Development and IndustrialPharmacy 36 128ndash42
Rekhi G S Porter S C and Jambhekar S S (1995) Factors affectingthe release of propranolol hydrochloride from beads coated with aque-ous polymeric dispresions Drug Development and Industrial Pharmacy21 709ndash29
Sadeghi F Ford J L Rubinstein M and Rajabi-Siahboomi A R(2001) Study of drug release from pellets coated with surelease con-taining hydroxypropyl methylcellulose Drug Development and IndustrialPharmacy 27 419ndash30
Savage G V and Rhodes C T (1995) The sustained release coating ofsolid dosage forms A historical review Drug Development and Indus-trial Pharmacy 21 93ndash118
Seitz J A Swarbrick J and Boylan J C (1988) Aqueous film coat-ing Encyclopedia of Pharmaceutical Technology Marcel Dekker NewYork pp 337ndash49
Singh P Solanky T K Mudryya R Pfefferc R and Davea R (2001)Estimation of coating time in the magnetically assisted impaction coatingprocess Powder Technology 121 159ndash67
Syloidreg FP silica excipientsmdashmore than just Silica (Belgium Fred Mon-suur Grace Davison Discovery Sciences) (13 September 2010)
Systems GNP (2012) SUPERCELLtrade Tablet Coating Technology (SCT)Niro Inc 9165 Rumsey Road Columbia MD 21045 USA
Wu C and McGinity J W (2001) Influence of Ibuprofen as a solid-state plasticizer in Eudragit RS 30D on the physicochemical propertiesof coated beads AAPS PharmSciTech 2 1ndash9
Zheng W and McGinity J W (2003) Influence of Eudragit NE 30 Dblended with Eudragit L 30 D-55 on the release of phenylpropanolaminehydrochloride from coated pellets Drug Development and IndustrialPharmacy 29 357ndash66
