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International Journal of Universal Pharmacy and Bio Sciences 3(1): January-February 2014

INTERNATIONAL JOURNAL OF UNIVERSAL

PHARMACY AND BIO SCIENCES IMPACT FACTOR 1.89***

ICV 5.13*** Pharmaceutical Sciences REVIEW ARTICLE……!!!

FAST DISSOLVING ORAL FILMS: NOVEL WAY FOR ORAL DRUG

DELIVERY

Pardeep Kumar Jangra*1, Sachin Sharma

1, Rajni Bala

1

1Rayat Institute of Pharmacy, Railmajra, SBS Nagar, Punjab, India.

KEYWORDS:

Quick Dissolving Films,

Solvent Casting Method,

Enhance Bioavailability,

Quick Onset of Action.

For Correspondence:

Pardeep Kumar

Jangra*

Address:

Rayat Institute of

Pharmacy, Railmajra,

SBS Nagar, Punjab,

India.

Email:

pardeepjangra1988@gma

il.com

Mobile No. +91-

7696027996.

ABSTRACT

Fast dissolving films (FDF) are gaining interest as a substitute of fast

dissolving tablets. FDF are oral solid dosage form, designed to

dissolve within few seconds as they come in contact with wet

environment of the oral cavity. They quickly disintegrate and

dissolve, and there is no need of water for their administration,

making them suitable for paediatrics and geriatric patients. The oral

cavity is highly preferred route of administration as the mucosa is

highly enriched with blood supply, it provide an excellent site for

absorption of many drug directly into systemic circulation therefore

it leads to faster onset of action as well as degradation in GI tract and

first pass effect can be avoided. FDFs are prepared using hydrophilic

polymers that rapidly dissolves in the oral cavity delivering the drug

to the systemic circulation. Water soluble polymers are used in FDF

as they achieve rapid disintegration. Plasticizer helps to enhance the

flexibility of the strip and reduces the brittleness of the strip. Saliva

stimulating agent, sweetening agent, colours and flavours are added

in FDF as excipients. Solvent casting method is commonly used for

FDF preparation. Films prepared should be evaluated for

organoleptic properties, thickness, tackiness, tensile strength, folding

endurance, disintegration and dissolution.

mailto:[email protected]

mailto:[email protected]



INTRODUCTION:

Oral route is the most commonly used and acceptable drug delivery route among all other delivery routes.

Orally disintegrating tablets are available in the market which disintegrates in one to two minutes, whereas

FDF are capable to disintegrate within few seconds. Initially FDF were introduced in the market as

personal care and breathe freshener products, later their importance for therapeutic benefits was observed1.

First therapeutic FDF was Chloraseptic®, containing 7-benzocaine for the treatment of sore throat was

launched in the market. FDF consists of a thin film, which is placed on the patient‟s tongue or mucosal

tissue, film gets wet by saliva and dissolves rapidly. This fast dissolving action is mainly because of the

large surface area of the film which wets quickly when exposed to moist environment of the oral cavity.

FDF is an alternative to traditional oral solid dosage forms like tablets, capsules, syrups etc. This dosage

form was developed from the technology of the transdermal patch2. FDF is prepared using hydrophilic

polymer that rapidly dissolves, delivering the drug to the systemic circulation via buccal mucosa and as the

drug released by FDF is directly delivered to the systemic circulation so it leads to faster onset of

therapeutic action. FDF dosage form is primarily formulated for the drugs which have low bioavailability

due to extensive first pass metabolism, for the enhancement of bioavailability3. FDF is useful in paediatric

and geriatric patients as they have difficulty in swallowing conventional oral dosage forms resulting in

poor patient compliance. FDF are getting good response and acceptance from patients as they can be self-

administered even without water uptake and their onset of action is faster as compared to other

conventional oral solid dosage forms like capsules, tablets etc.

CLASSIFICATION OF ORAL FILMS:

Oral films are of following three types:

1. Flash release wafer

2. Mucoadhesive melt away wafer

3. Mucoadhesive sustained release wafer4.



TABLE 1: TYPES OF ORAL FAST DISSOLVING FILMS AND THEIR PROPERTIES4

Property/Sub

Type

Flash Release Wafer Mucoadhesive

Melt-Away Wafer

Mucoadhesive Sustained

Release Wafer

Area (cm2) 2-8 2-7 2-4

Thickness (µm) 20-70 50-500 50-250

Structure Film: single layer Single or multilayer

System

Multi layer system

Excipients Soluble, highly

hydrophilic polymers

Soluble, hydrophilic

Polymers

Low/Non-soluble

Polymers

Drug phase Solid solution Solid solution or suspended

drug particles

Suspension and/or solid

Solution

Application Tongue (upper palate) Gingival or buccal

Region

Gingival, (other region in

the oral cavity

Dissolution Maximum 60 seconds Disintegration in a few

minutes, forming gel

Maximum 8-10 hours

Site of action Systemic or local Systemic or local Systemic or local

Criteria for selecting a suitable drug candidate:

Drug should have pleasant taste.

Therapeutic dose of the drug should not be greater than 40mg.

Drug should have good solubility in water and saliva.

It should be stable in water.

Drug should be partially unionized at oral cavity pH.

Drug should have small molecular size and low molecular weight.

Drug molecule should have the capability to permeate oral mucosa4.

Advantages of Fast Dissolving Films:

Improved oral bioavailability of drug as hepatic first pass effect is reduced.

Fast onset of action as drug enters directly in the systemic circulation.

No fear of obstruction or chocking.

No need of water during film administration.

Reduction in dose of the drug.

Taste masking.

Improved patient compliance.

Enhanced stability.



Large surface area film lead to quick disintegration and dissolution within oral cavity.

Available in various sizes and shapes4, 5

Disadvantages of Fast Dissolving Films:

Drugs whose therapeutic dose is greater than 40mg cannot be incorporated in the film.

Packaging of films is difficult and it requires special equipments.

Challenge of maintaining dose uniformity in films.

Technical limitation of maintaining uniform thickness of film while manufacturing on large scale.

Ideal properties of Fast Dissolving Films:

Films should have good mechanical strength and should be less fragile.

Should have acceptable pleasant taste.

Film should quickly dissolve and release the drug instantly.

After oral administration film should leave very small or no residue in mouth.

Should disintegrate fast even without water6.

ORAL MUCOSA:

The main role of oral mucosa is protection of tissue underlying. Lipid based permeability barriers in

epithelium layer protect the tissues from fluid loss and also from the attack of harmful environmental agents

like microbial toxins, antigens, carcinogens, enzymes, etc7. The turnover time for oral epithelium

proliferation is 5-6 days8.

FIGURE 1: ORAL MUCOSA



1. Structure and composition:

Oral mucosa contains following three layers of cells7:

i. Epithelium:

It‟s the outermost layer of the oral cavity. It contains 2 type of stratifying squamous epithelium cells –

keratinized and non-keratinized epithelium. Keratinized epithelium is present on hard palate region whereas

soft palate contains non-keratinized epithelium and its more flexible and elastic as compared to keratinized

epithelium. Basement membrane is the interface between connective tissue and epithelium.

ii. Lamina propria:

It‟s a connective tissue present below basement membrane, supports the epithelium membrane and mainly

consists of cells and blood vessels.

iii. Submucous membrane:

Submucous membrane or submucosa is the innermost layer of oral cavity. It is a loose connective tissue

which contains major blood vessels and nerves. It separates the oral mucosa from underlying bone.

2. Permeability:

Permeability of oral cavity is greater than skin but less than that of intestine mucosa. Oral mucosa is 4-4000

times more permeable as compared to skin9. Oral cavity has variable water permeability in its different

regions. Keratinized epithelium is less water permeable and it is present in hard palate region, whereas non-

keratinized epithelium is more water permeable and it is present in soft palate region of the oral cavity.

Membrane coating granules (MCG) are present in both keratinized and non-keratinized epithelia; they

contain polar lipids, glycoprotein and hydrolytic enzymes. They are responsible for permeability barrier of

oral epithelia to a greater extent. To enhance the permeability, oral permeability enhancers like

benzalkonium chloride, menthol, etc. can be added which will increase the drug absorption significantly5, 7

.

DRUG RELEASE:

The drug release mechanism is simple and its rate depends on the type of polymer selected. Hydrophilic

polymers are preferred over other types of polymers. The film is placed on the patient‟s tongue and it

instantly gets wet by saliva, it happens because of the hydrophilic polymer which enhance the wetting

ability of film as the amount of polymer in film is high (40-50% w/w). After few seconds the film gets

completely dissolved and the drug is released5.

DRUG ABSORPTION:

Drug absorption process across the oral mucosa primarily follows first order simple diffusion process.

Transcellular and paracellular are the two routes through which the drug can be absorbed from the oral



mucosa. In transcellular the drug molecules pass through the cell whereas in paracellular the drug molecule

passes through the space between two cells. Physiochemical properties of the drug decide the route to be

followed by the drug molecules but mainly permeation occurs by paracellular route. Lipophilic drug

molecules pass by the transcellular route whereas hydrophilic drug molecules permeate through paracellular

route. Small drug molecules, mainly lipophilic ones are more rapidly absorbed than large hydrophilic

molecules, and as the drug molecule size increases permeability decreases10

.

APPLICATIONS OF FAST DISSOLVING FILMS:

Fast dissolving films deliver drug to systemic circulation through oral mucosa via sublingual, buccal and

mucosal route. As this drug delivery method provides rapid absorption of drug in blood and leads to faster

onset of action so this can be useful in treatment of allergies, to manage pain, insomnia and CNS

disorders11

. Antitussive, antiasthmatics, expectorants, antihistaminic, antiepileptic agents, etc can be

incorporated in films which are then released in the oral cavity1. In the coming years fast dissolving films

will play more broad and important role in drug delivery.

FORMULATION COMPOSITION:

Formulation of FDF should be done carefully as it‟s the most important step. Formulation composition

affects the characteristics of the film. It affects the aesthetic, performance and physical characteristics of the

film, like taste masking, mouth feel etc., so selection of each ingredient or constituent becomes a challenge.

While selecting composition ingredients, their all physical and chemical properties should be studied and

their compatibility with the drug should be checked. All the excipients to be used in the formulation should

be GRAS-listed (i.e. Generally Regarded as Safe) and should be approved for oral use in pharmaceutical

dosage forms. A typical composition contains following ingredients:

TABLE 2: FORMULATION COMPOSITION

S. No. INGREDIENTS AMOUNT

1. Drug / Active Pharmaceutical Ingredient 5-30%

2. Film forming polymer 40-50%

3. Plasticizer 0-20%

4. Saliva stimulating agent 2-6%

5. Sweetening agent 3-6%

6. Stabilizing and thickening agent 0-5%

7. Flavouring agent q.s.

8. Surfactant q.s.

9. Colouring agent q.s.



1. Active Pharmaceutical Ingredient:

Drug from different classes can be incorporated in FDF. But as the size of the film is small so only

small quantity of drugs can be incorporated, generally drugs having therapeutic dose up to 40mg are

be added in films. Quantity of active pharmaceutical ingredient incorporated in FDF formulation is

5-30%w/w of the total weight of the dry film12

. Texture and dissolution of the film can be enhanced

by using micronized API, it will also improve the uniformity in the film. If the taste of drug is not

acceptable or bitter than it becomes necessary to mask the taste of the drug, for this obscuration

technique, barrier techniques including complexation, polymeric coating, conversion to

microparticles, coated particles or coated granules etc. can be used. In complexation bitter API gets

surrounded by cyclodextrins or resins which prevents the direct contact with saliva13

. Some

examples of drugs which can be good candidate of the FDF formulation are given below.

TABLE 3: DRUG MOLECULES ELIGIBLE FOR INCORPORATION IN FDF

Drug Therapeutic Category Dose (mg)

Acrivastine Anti histaminic 8

Famotidine Antacid 10

Ketoprofen Analgesic 12.5

Nicotine Smoking cessation 2

Nitroglycerin derivative Vasodilator 0.3-0.6

Ondensetron Anti emetic 2.5

Dicyclomine hydrochloride Muscle relaxant 25

Flurazepam Anticonvulsant 15-30

Zolmitriptan Anti migraine 2.5

2. Film Forming Polymer:

It is the most important and major ingredient of FDF. Its quantity in the FDF formulation is 40-

50%w/w of the total weight of the dry film, but 60-65%w/w concentration of polymer is preferred to

obtain desired properties. Polymers can be used alone or along with other polymer in combination to

get the desired properties of the film. Robustness of film depends on the type and amount of

polymer used in the formulation. Hydrophilic polymers which rapidly dissolve when come in

contact with saliva in oral cavity are used as film forming polymer. The rate of disintegration of

polymers decreases with increase in their molecular weight. Hydrophilic polymers give faster

disintegration, good mechanical properties and good mouth feel to the films14, 15

.



Ideal properties of the film forming polymers:

Polymer should be non-toxic and non-irritant.

It should not contain any leachable impurity.

It should have good wetting and spreading properties.

Should not cause secondary infection in the oral mucosa.

Good mouth feel property.

Polymer should have considerable peel, shear and tensile strengths.

Good shelf life.

Desired to have local enzyme inhibition property with penetration enhancement action.

Both natural and synthetic polymers are used for the preparation of FDF. Few examples of polymers used

are given below:

TABLE 4: LIST OF FILM FORMING POLYMERS

S.No. Natural polymer Synthetic polymer

1. Pullulan Hydroxy propyl methyl cellulose

2. Starch gelatin Polyvinyl pyrolidone

3. Pectin Polyvinyl alcohol

4. Sodium alginate Carboxy methyl cellulose

5. Maltodextrin Poly ethylene oxide

6. Polymerized rosin Kollicoat

7. Lycoat NG 73 Hydroxypropyl cellulose

8. Xanthan Hydroxy ethyl cellulose



Various properties of few film forming polymers are listed below:

TABLE 5: PROPERTIES OF FEW FILM FORMING POLYMERS

Property HPMC Gelatin Pullulan Kollicoat Starch and modified

starch

Molecular weight 10,000-

1,500,000

15,000-

250,000

8,000-

2,000,000

About

45,000

50,000-160,000

Solubility Soluble in

cold water,

insoluble in

chloroform,

ethanol.

Soluble in

glycerine, acid

and alkali,

swell in water.

It is soluble in

hot as well as

in cold water.

50% in

water.

Insoluble in cold water

and ethanol. Swells in

water by about 5-10% at

37oC.

Film forming

ability

It has film

forming

capacity in 2-

20%w/w

concentration.

Very good film

forming

capacity.

High

adhesion and

film forming

capacity.

Good film

forming

properties.

Good film forming

capacity.

Melting point 190-200oC - 107

oC - 250

oC

pH 5-8 3.8-6.0 5-7 6.7 -

3. Plasticizer:

Plasticizers provide flexibility and reduces the brittleness of the film. It improves the properties of

the film by reducing glass transition temperature of the polymer. It also improves the tensile

strength and film elongation property. Selection of plasticizer depends on the polymer and type of

solvent to be used in casting the film. Plasticizer selected should be compatible with the drug, film

forming polymer as well as with other excipients used in the film. Use of inappropriate plasticizer

can lead to film cracking, peeling and splitting. They are used in the concentration of 0-20%w/w of

dry film16

. Some commonly used plasticizers are polyethylene glycol 400, glycerol, castor oil,

citrate ether, propylene glycol, etc.

4. Saliva stimulating agent:

Disintegration and dissolution of the oral film depends on the amount of saliva present in the oral



cavity. Sometimes quantity of saliva in mouth can be low, it can be due to some disease as well so

to overcome this saliva stimulating agents are added in the formulation. Saliva stimulating agents

are added in the film to increase the production of saliva which will help in faster disintegration of

the film. Their concentration in the formulation is 2-6%w/w of dry weight of the film. In general,

acids used in the food industry are used as saliva stimulant. Commonly used stimulants are citric

acid, ascorbic acid, lactic acid, malic acid and tartaric acid. These can also be used in combination17

.

Synthetic sugars and food grade sugars can also used as saliva stimulant. Few examples of such

sugars are glucose, fructose, lactose, etc.

5. Sweetening agent:

Sweeteners are added to enhance the palatability of the oral films. Sweet taste is essential in films

prepared for paediatrics patients. Natural as well as artificial sweeteners can be used in the

concentration range of 3-6%. They can be used alone or in combination18

.

Some examples of natural and artificial sweeteners are given below:

TABLE 6: LIST OF SWEETENING AGENTS

Generally artificial sweeteners are preferred as low concentration of sweetener is required as

compared to natural sweeteners. Use of natural sugars is prohibited in diabetic patients. Artificial

sweeteners have a disadvantage that they leave after taste effect. It can be reduced by adding natural

sweetener.

6. Stabilizing and thickening agents:

They are used to enhance the consistency and viscosity of film solution before casting. Natural

gums like carrageenan, xanthan gum and cellulosic derivatives can be used in concentration up to

5% w/w as stabilizing and thickening agents19

.

7. Flavouring agent:

Flavour acceptance changes from person to person depending on the ethnicity and liking. Age also

play significant role in taste fondness. Geriatric patients like mint or orange flavors while younger

S.No. Natural Sweeteners Artificial Sweeteners

1. Glycyrrhizin Saccharin

2. Xylose Aspartame

3. Ribose Polyhydric alcohols

4. Glucose Cyclamate salts

5. Sucrose Acesulfame-K



patients like fruit punch, raspberry etc. flavor selection depends on the type of drug to be

incorporated in formulation.

TABLE 7: LIST OF FLAVOURING AGENTS

Amount of flavor needed depends on the type of flavour and its strength. Generally upto 10% w/w

concentration of flavor is added in FDOF formulation14

.

8. Surfactants:

Surfactants are used to increase wettability and dispersibility of the film so that film gets dissolved

within seconds and release the drug instantly. They also act as solubilising agent. Commonly used

surfactants are polaxamer 407, sodium lauryl sulphate, benzalkonium chloride, bezthonium

chloride, tweens etc20

.

9. Colouring agent:

Natural colouring agents and natural juice concentrations approved by FD&C are most commonly

used in FDOF. Their concentration should not exceed 1%. Pigments like silicon dioxide, titanium

oxide can also be used as colouring agents.

METHODS OF PREPARATION:

Following methods can be used for the preparation of fast dissolving oral films:

1. Solvent casting method

2. Semisolid casting method

3. Hot melt extrusion

4. Solid dispersion extrusion

5. Rolling method

1. Solvent Casting Method: It is very old film making method. In this method the drug is either

dissolved or suspended in a solution containing polymers, plasticizers and other excipients which are

dissolved in a volatile solvent, like ethanol or water. It is referred as film dope, it is then casted in petri

plate and passed through drying equipment like oven to remove all the volatile solvents. Then the dried

film is die cut into strips and packed in sealed atmospherically resistant pouches. This method is

suitable for films containing heat sensitive drug/API as the temperature needed to remove the volatile

solvents is comparatively low than hot melt extrusion method21

.

Synthetic flavor oils: Peppermint oil, cinnamon oil, spearmint oil, nutmeg oil.

Fruity flavors: Vanilla, cocoa, coffee, chocolate and citrus.

Fruit essence: Apple, raspberry, cherry, pineapple.



Advantages:

i. Better film clarity and thickness uniformity than extrusion method.

ii. Fine gloss on film and lack of die lines.

iii. Films with more flexible and better physical properties are produced by this method.

Disadvantages:

i. Polymers to be used should be soluble in volatile solvents.

ii. Formation of a stable solution with considerable minimum solid content and viscosity is

required, which is difficult to attain.

iii. Homogenous film preparation with proper drug release from casting support must be attained.

FIGURE 2: SOLVENT CASTING METHOD

2. Semisolid Casting Method: Semisolid casting method is generally used when acid insoluble polymers

are used. In this method a solution of water soluble film forming polymer is made then this solution is

poured in the solution of acid insoluble polymer, which is prepared in sodium or ammonium hydroxide.

After this plasticizer is added to form the gel mass. Amount of plasticizer added affect the property of

gel mass formed. The gel mass formed is then casted into film or ribbons using heat controlled

rollers/drums. The ratio of acid insoluble polymer and film forming polymer should be 1:4. The films

thickness formed by this method is about 0.015-0.05 inches4.

3. Hot Melt Extrusion: This method involves shaping polymer into film through heating process.



Firstly the drug - polymer mixture is filled in hopper and is conveyed, mixed & melted by the

extruder. A die gives shape to the melt in required form. This method involves lower temperature

and short residence time (< 2 min.) for the drug polymer mixture. Organic solvents are not used

in this method and it can operate continuously with minimum product wastage. Operating

parameters can be controlled efficiently by this method12.

FIGURE 3: HOT MELT EXTRUSION METHOD

Advantages:

i. Less processing steps.

ii. No need of solvent or water.

iii. Less energy is required compared to high shear methods.

iv. Uniform dispersion of fine particles due to intense mixing and agitation.

v. No importance of drug compressibility properties.

Disadvantages:

i. Number of polymers is limited.

ii. Polymer flow properties are essential to processing.

iii. Drug/polymer stability problem as it is a thermal process.

4. Solid Dispersion Extrusion: Term solid dispersion refers to dispersion of active ingredients in an inert

carrier in solid state in the presence of amorphous hydrophilic polymers. In starting, the drug is

dissolved in suitable liquid solvent and later this solution is added in the melt of polyethylene glycol at

below 70oC without removing the liquid solvent. The drug or solvent may not be miscible with melt of

polyethylene glycol. And at last the solid dispersions are passed through dies to shape them in form of

film12

.



Advantages:

i. Low shear method.

ii. Uniform dispersion of fine particles.

iii. Less processing steps.

5. Rolling Method: In rolling method a pre-mix is prepared for preparation of film, later active drug is

added and film is prepared. Pre-mix batch include film forming polymer, polar solvent, plasticizer and

other excipients except the drug, which is added in to the master batch. Master batch and pre-mix of

required quantity are pumped into separated containers and later drug is blended with master pre-mix

for specific time to provide uniformity. The mixture so formed is then fed to the roller; metering roller

controls the thickness and applies the mixture to the roller. The film is formed and it is carried away by

the support roller. As the film formed is wet so it is then dried using controlled bottom drying, it is

desirable to avoid presence of external air while drying. After drying, film is cut into different sizes and

shapes according to need22

.

FIGURE 4: ROLLING METHOD

Table 8: Comparison of Solvent Casting Method and Hot Melt Extrusion Method

Factor Solvent Casting Method Hot Melt Extrusion

API selected Thermolabile, thermostable Thermostable

Solvent required Yes No

Process Hydrous Anhydrous

Equipment required Rollers, coaters Hot melt extruder

Scale-up May create problems May not be difficult

Chance of air entrapment High chance Low chance



DRUG-EXCIPIENTS INTERACTION STUDIES:

It is important to detect all types of possible interactions between drug and excipients as these interactions

can lead to incompatibility and the dosage form will not be stable. These types of interactions can be

detected by using Fourier Transformer Infra-Red Spectrum (FTIR), Differential Scanning Calorimeter

(DSC), thin layer chromatography and X-Ray Diffraction (X-RD) techniques. DSC is the fastest method of

evaluation of interactions, because it shows changes in appearance or physical property, shift or melting

endotherms and exotherms, and variations in the enthalpies of reaction.

EVALUATION PARAMETERS:

1. Organoleptic Evaluation:

Organoleptic properties like colour, odour and taste play important role in acceptance of formulation by

patients. Colour of the formulation should be acceptable; it provides means of identification or

differentiation for different pharmaceutical products. Colour of the film should be uniform. Odour of the

film should not be unpleasant. Odour presence can also indicate stability problem. Presence odour may be

characteristic of drug. Taste is the most important factor in acceptance of the formulation by patients. Some

companies judge the taste of the formulation prepared using different flavours; they use a taste panel to

choose the formulation with best acceptable flavour and flavour level. So FDOF prepared should have good

acceptable organoleptic properties23

.

2. Weight Variation:

Film prepared is cut from different areas into 5 patches of one square inch each. Every patch is weighed and

average weight is calculated. Then the weight variation of film patch can be determined. It‟s necessary that

every film patch have minimum weight variation as weight variation can lead to difference in dose of the

drug in films and in potent drugs films it can be very harmful24

.

3. Thickness:

It‟s a necessary point of evaluation as it is directly related to the dose accuracy of drug in the film.

Thickness of the film can be measured using a micrometer screw gauge. Thickness is measured at 3-5

different strategic locations of film and then mean value is calculated, which is the final thickness value of

film25

.

4. Folding Endurance:

Folding endurance can be defined as the ability of the film to withstand against the harsh conditions of

transportation and handling. It can be determined by folding the film repeatedly from the same place until it



breaks or visible cracks can be observed. The number of times film folded without breaking is the value of

folding endurance16

.

5. Dryness/Tack Test:

Tack is defined as the tenacity with which the film gets adhered to an accessory like a piece of paper that

has been pressed to contact with the film. Various instruments are available to perform the dryness or tack

test. Eight stages of film drying process have been identified which are set-to-touch, dust-free, tack-free,

dry-to-touch, dry-hard, dry-through (dry to handle), dry to recoat and dry print free. Although, all these tests

are mainly used only for paint films, but most of the studies can be adapted also for the evaluation of oral

films13

.

6. Surface pH:

Surface pH of film can cause irritation to the oral mucosa when placed in mouth if its pH is too acidic or

alkaline, so it‟s important to determine surface pH of the film. Surface pH of the film should be neutral i.e.

7 or should be close to 7. A combined pH electrode can be used to determine surface pH. The film is made

slightly wet with water and the electrode is brought in contact with film and the pH reading is noted. This

test is applied on at least 6 films and the average is taken which is the final value of surface pH4.

There is one more method to determine the surface pH; in this the film is left for swelling on surface of agar

plate. Agar plate is prepared by dissolving 2% w/v agar in warm phosphate buffer solution of pH - 6.8 with

continuous stirring and the final solution is poured in petri dish and left to solidify at room temp. The

surface pH can be measured using pH paper, pH paper is placed on surface of swollen film and change is

colour gives the value of surface pH of the film. The average of three readings should be taken26

.

7. Swelling Index:

Each film is weighed and placed separately in petri dishes containing phosphate buffer pH - 6.8 (5ml in

each petri). Dishes should be stored at room temperature, then films are taken from petri dishes after

specific time and their excess surface solution should be removed gently using filter paper. Swollen films

are then weighed and selling index is calculated using the formula given below26

:

Swelling Index SI =Wt - Wo

Wo

Where Wt is weight of the film at time„t‟ and Wo is weight of the film at t = 0.

8. Percent Elongation:

Whenever stress is applied on the film it starts stretching and it is called as strain. Strain is the deformation



of the film divided by the original dimension of the film sample. Elongation parameter of film is directly

related to the amount of plasticizer used or incorporated in the film. Elongation increases with increase in

amount of plasticizer.

It can be calculated from following formula13

:

Percent Elongation =Increase in length of film × 100

Initial length of film

9. Tensile Strength:

Tensile strength is the ability of being stretched. Film should have good tensile strength. To determine film

is pulled using pulley system. Weight is gradually increased at one end of the film and the weight at which

the film breaks is noted, it is generally called load of failure.

It is calculated by using the following formula which is load applied at breakage divided by cross section

area of the oral film5, 26

:

Tensile Strength =Load at failure × 100

Film thickness × Film width

10. Young’s Modulus:

Young‟s modulus or elastic modulus is measure of the degree of stiffness of the film. Method used for its

measurement is similar to that of tensile strength. It measures the resistance offered to deformation and

observed by plotting the stress strain curve where slope gives the modulus. Films hard and brittle in nature

have high tensile strength and Young‟s modulus value27

. Young‟s modulus is the ratio of applied stress over

strain in region of elastic deformation; mathematically it can be calculated using the following formula19

:

Young′s Modulus =Slope × 100

Strip thickness × Cross head speed

11. Tear Resistance:

Tear resistance is the ability of the film against the force applied to tear or rupture it. A very low rate of

loading i.e. 51mm (2in.)/min. is applied and it is designed to measure the force to starting tearing of film.

The maximum force required for tearing the film is noted as the tear resistance value in Pounds-force or

simply Newtons. In stress strain curve, the area of the plot gives the tear resistance27

.

12. Contact Angle:

Contact angle gives information about wetting behaviour, dissolution and disintegration of the oral film.

Goniometer is used to measure the contact angle at room temperature4. A dry film sample is taken and a



drop of distilled water is placed on surface of the dry film. Images of water droplet are taken by digital

camera within 10 sec. just after placing the droplet on the film. Digital pictures should be analysed by

image J 1.28v software (NIH, USA) for determination of angle. Contact angle should be measured on both

sides of the water droplet and their average is taken Minimum five measurements are taken at different

positions of the film12, 16

.

13. Transparency:

UV spectrophotometer is used to determine the transparency of the film. Film specimen is taken and placed

in the spectrophotometer cell and analysed at 600nm. Transparency can be calculated using the following

formula:

Transparency = (log T600)/B = -€C

Where T600 is transmittance at 600nm, b is thickness of the film and C is concentration3.

14. Drug Content Uniformity:

Drug content uniformity test is done to check whether same amount of drug is equally distributed in every

film or not. For this test, a patch of film (size 2×2cm2) is taken and placed in a beaker containing 100ml

phosphate buffer (pH - 6.8). Medium is stirred for proper dissolution on magnetic stirrer for 6 hours. Later

the content is filtered using Whattman filter paper and the filtrate sample is analysed by UV

spectrophotometer at specific wavelength according to the drug incorporated in the film28

. Drug content can

be determined by plotting a standard calibration curve of drug in phosphate buffer (pH - 6.8)24

. The limit of

content uniformity is 85-115%.

15. Percentage Moisture Loss:

This test is done to determine the integrity and physical stability of the film. To determine the percentage

moisture loss of the film a film patch of size 2×2 cm2 is cut and weight preciously. After that the film patch

is placed in a desiccator containing fused anhydrous calcium chloride for three days. After three days film

patch is taken out and weighed again and the percentage moisture loss of the film is calculated using the

following formula26

:

Percentage Moisture Loss =(Initial Weight− Final Weight)

Initial Weight× 100

16. In-vitro Disintegration Study:

Disintegration study helps us in determining the time required by the film to completely disintegrate in the



oral cavity. This is performed by USP disintegration apparatus. For FDOP disintegration time should be in

a range of 5-30 sec. for good results.

There is one more method for determining the disintegration time of films; in this the disintegration time

can be visually determined by simply immersing the film of 4cm2 area in 25ml of water in a beaker. Beaker

containing film should be gently shaken and the time is noted when the film start breaking or

disintegrating4, 29

.

17. In-vitro Dissolution Studies:

Amount of drug which gets dissolve and goes in the solution per unit time under standard conditions of

temp., solvent concentration and liquid/solid interface is called dissolution. It‟s difficult to perform

dissolution study of oral film as they can float over the dissolution medium when paddle type dissolution

apparatus is used, so basket type dissolution apparatus is mostly used. Selection of the dissolution media

depends of the sink conditions and the highest dose of drug/API. During dissolution the temperature of the

medium should be 37 ± 0.5oC and speed of rotation of basket or paddle should be 50 RPM

4.

In other method release of drug is studied on a film of 4cm2 area. In a beaker, film is adhered to side wall of

beaker using a cyanoacrylate adhesive and sink condition is provided by placing 50ml phosphate buffer

solution (pH - 6.8) in the beaker. The solution in beaker is stirred continuously using magnetic stirrer at 150

RPM. After time intervals of 20, 40, 60, 80, 100 and 120 sec. 3ml of sample is taken and filtered through

whattman filter paper and assayed spectrophotometrically to calculate the drug content released at that time.

After taking each sample same amount of phosphate buffer is added in the beaker to keep the volume of the

medium constant26

.

18. In-vitro Release Kinetics:

Data collected from in-vitro dissolution studies is added or fitted in different kinetic models like zero order

as cumulative percent of drug dissolved vs. time, first order as log cumulative percentage of drug remaining

vs. time and the Higuchi‟s model as cumulative percent drug dissolved vs. square root of the time to

establish a relation between the relation between release kinetics of the dissolution study. Similarly to find

out the mechanism of drug release, data is fitted in Korsmeyer and Peppas equation as log cumulative

percentage of drug release vs. log time and the exponent n can be calculated from slope of the straight line.

For the slab matrix if exponent is 0.5, then diffusion mechanism is Fickian, if its 0.5<n<1.0, then

mechanism is designated as Non-Fickian26, 30

.

19. Scanning Electron Microscopy:

Scanning electron microscopy is an important tool to study the surface morphology of the oral film.



Different excipients added in formulation affect the surface morphology of film differently which affect

various parameters of the film. A film sample is taken and placed in sample holder of SEM at 1000X

magnification and various photomicrographs can be taken using the tungsten filament as source of electron.

Then the photomicrographs taken can be analysed4.

STABILITY STUDIES:

It is important to perform stability testing of the formulation prepared to check whether it is a stable product

or not and to see if it will be able to maintain its integrity during its shelf life. International Conference on

Harmonization (ICH) has laid down guidelines for the stability testing of various pharmaceutical products

and stability study of FDOF should also be carried out according ICH guidelines. The formulation prepared

should be packed in a special way, firstly the formulation is wrapped in a butter paper then aluminium foil

is wrapped over it, then this is packed in an aluminium pouch and heat sealed. Storage conditions of

formulation should be 45oC/75%RH. Formulations should be stored for 3 months. During the course of

stability study triplicate samples are taken at three sampling intervals i.e. 0, 1 and 3 month, and films should

be evaluated for physical changes and drug content4, 26

.

PACKAGING OF FAST DISSOLVING ORAL FILMS:

It is necessary that every pharmaceutical product should be properly packed and the material used for

packaging is stable and non-toxic. Packaging methods available today vary widely and are much trustable

methods used decades ago. Basic need of packaging is that it should preserve the packed product in its

original form or we can say it should preserve the integrity of the pharmaceutical product. Packaging should

be done very carefully. It requires special care and specific processing during packaging and storage of

FDOF. Today various packaging options are available for FDOF. For pharmaceutical FDOF products single

packaging is mandatory and aluminium pouch is the best and commonly used packaging method. Recently

APR-Labtec developed a new way of packaging called „Rapid Card‟, it is a patented and proprietary

packaging system, it is especially made for rapid films. Its size is same as that of a credit card and contains

three rapid films on each side of the card. And in future we will see new ways of packaging31

.

Stability and integrity is directly related to the material selected for packaging of the product. The material

selected for packaging must have following properties:

Must protect the product from external environment.

Must not impart or change the taste and odour of the product.

Material should be FDA approved.

Should be non-toxic in nature.



Should be tamper resistant.

It should not react with the packed product.

Various methods used for packaging of FDOF are given below:

1. Single Pouch and Aluminium Pouch: The Soluble film drug delivery pouch is peelable type pouch

used for the FDOF, which have high barrier property. Pouches are generally transparent for the

product display. It is done by using a 2 structure combination method in which one side is clear and

other is cost effective foil lamination which is not clear. Foil lamination provides no transmission of

moisture and gas which does not allow the degradation of the product packed. Aluminium pouch is

commonly used for packaging of films.

2. Blister Card with multiple units: Blister card contains two components i.e. the blister, it‟s the

cavity which holds the product to be packed and the lid stock which seals the blister packing. The

blister cavity is formed by softening the thermoplastic resin sheet with heat and then vacuum

drawing the softened sheet in the mould. Later the sheet is cooled and released from the mould for

filling at filling station of packaging machine. Blister formed previously is filled with product and

lidded with the backing material which is heat sealed. Selection of the film material depends upon

the degree of protection needed. Generally plastic is used to form the cavity; it provides protection

to dosage form against moisture32

.

3. Continuous Roll Dispenser: It is a small reusable portable dispenser unit which contain an

automatic drug tape dispensing and metering device & a disposable cassette containing a roll of

drug tape. A measurement device is fitted in it which preciously measures the length of the drug

tape to be dispensed. A timer device can also be fitted in dispenser so as to alert the patient about the

time when the drug tape or film is to be taken2.

4. Barrier Films: Some drug products are extremely moisture sensitive and require high barrier films

for protection. Materials like Polychlorotrifluoroethylene (PCTFE), polypropylene can be used to

provide protection against moisture. Polypropylene is an excellent barrier against vapour and gas

but its drawback is that it lacks clarity26

.

CONCLUSION:

Fast dissolving oral films are gaining popularity in the field pharmaceutical dosage forms as well as

mouth fresheners as their administration is easy. FDOFs can be taken by all type of patients

including children and geriatrics. Currently many pharmaceutical industries use FDOF for drug



delivery but this trend is going to increase more widely. FDOFs have various advantages over

conventional tablets, like no risk of obstruction during administration and no need of water for

uptake. Their onset of action is also faster than tablets so these can be used in some emergency cases

such as asthmatic attacks or allergic reactions. FDOFs preparation is ideal for drug having low

bioavailability as tablets because of first pass effect, as FDOF bypass the first pass effect and

increase the bioavailability of drug and dose of the drug can also be reduced. FDOF is a good

method to increase the product life cycle by getting patent of existing products as fast dissolving

films. In this review article an effort is done to combine all the information about fast dissolving

oral films and aware people related to pharmacy field about the advantages of Fast Dissolving Oral

Films.

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