PowerPoint Presentation

ByDr. Nehal Aly AfifiProf. of PharmacologyCairo Univ

Pharmaceutical Excipients

Pharmaceutical Excipients1/2/2016Prof. Dr. Nehal Afifi2

An excipient is a pharmacologically inactive substance formulated alongside the active pharmaceutical ingredient API of a medication. Purposes served by excipients: Provide bulk to the formulation. Facilitate drug absorption, solubility & other pharmacokinetic considerations. Aid in handling of API during manufacturing . Provide stability and prevent from denaturation .

1/2/2016Prof. Dr. Nehal Afifi3ExcipientsNo interaction with drugPharmacologically inertFeasible

Cost effectiveStable for handling

1/2/2016Prof. Dr. Nehal Afifi4A list of Excipients used in pharmaceutical Dosage Forms Fillers. - Antioxidants. Binders - Sweating Agents Disintegrants. - Flavoring Agents Coating agent. - Coloring agents. Sorbents. - Solvent. Antiadherent. - Co-solvent. Lubricants. - Chelating Agents Glidants. - Buffering agent. Humectants. -Surface Active Agents Preservatives. Viscosity imparting Agents

.

1/2/2016Prof. Dr. Nehal Afifi5 Fillers: Typically fill out the size of tablet or capsule, making it practical to produce & convenient for consumers to use. Function of fillers: Add volume and/or mass to a drug substance, so facilitating precise , metering & handling in compounding dosage forms . Used in tablets & capsules. Typical features of fillers: Fillers should be inert, Compactable, Non-hygroscopic, Compatible with other components of formulation, Cheap, preferably tasteless or pleasant tasting.

1/2/2016Prof. Dr. Nehal Afifi6 Examples: Plant cellulose &dibasic calcium phosphate Vegetable fats & oils used in soft gelatin capsules. Fillers may also be lactose, sucrose ,mannitol, sorbitol. Binders: Binders hold the ingredients in a tablet together . Ensure that tablets formed with required mechanical strength Give volume to low active dose tablets Should be compatible with other products of formulation Add sufficient cohesion to the powders Classification: According to their application 1-Solution binders dissolved in a solvent as water oralcohol 2- Dry Binders added to powder.

1/2/2016Prof. Dr. Nehal Afifi7 Binders Example include cellulose, methyl cellulose, polyvinylpyrrolidone and polyethylene glycol. Disintigrants: Substances added to drug formulation, to facilitate dispersion or breakup of tablets & contents of capsules into smaller particles for quick dissolution when comes in contact with water in GIT are called diintintigrants. Ideal properties of disintigrants: Good hydration capacity poor solubility , and poor gel formation capacity Example: Polyvinylpyrrolidone, Carboxymethyl cellulose and Sodium starch glycolate .

1/2/2016Prof. Dr. Nehal Afifi8 Coating Agent: Coating is a process by which essentially dry, outer layer of coating material applied to the surface of a dosage form and agents used in this process is called coating agents. Types: 3 Types of coating agents are used pharmaceutically. Film coating. Sugar coating. Compression coating. Function of coating agents: Protection, Masking, Ease of swallowing, Elegance, and Identification .

1/2/2016Prof. Dr. Nehal Afifi9 Sorbents: Materials that soak up oil from water are Sorbents Types & examples of sorbents: Natural sorbents- peat moss, sawdust, feathers, and anything else natural that contains carbon. Synthetic sorbents- polyethylene & nylon. Functions of sorbents: Used for tablet/capsule moisture-proofing by limited fluid sorbing (taking up of a liquid or a gas by adsorption in a dry state.

Antiadherents (Anti-sticking agents ): Prevent adhesion of the tablet surface to the die walls and the punches so counter the picking or sticking of tablet. Examples: magnesium stearate, talc & starch can be used as antiadherents .

1/2/2016Prof. Dr. Nehal Afifi10 Lubricants: Prevent ingredients from clumping together & from sticking to the tablet punches or capsule filling machine. Lubricants alsoensure that tablet formation & ejection occur with low frictionbetween the solid and die wall. Types: 1. Hydrophilic: Poor lubricants, No glidant or anti-adherent 2. Hydrophobic lubricants: Most widely used today because Good lubricants & effective at relatively low conc. Also have both anti- adherent & glidant properties. Hydrophobic lubricants used more frequently than hydrophilic E.g.; magnesium stearate, Stearic acid, Polyethylene glycol. 1- True Lubricant Role: To decrease friction at the interface between a tablets surface and the die wall during ejection. 2- Anti-adherent Role: Prevent sticking to punch faces or in case of encapsulation, lubricants; Prevent sticking to machine. 3. Glidant Role: Enhance product flow by interparticulate friction

1/2/2016Prof. Dr. Nehal Afifi11 Glidants: A substance that enhance the flow of a granular mixture by reducing interparticle friction & used in the production of tablets & capsule. Functions: Glidants used to promote powder flow via interparticle friction. Used in combination with lubricants as they have no ability to reduce die wall friction. Examples: Fumed silica,talc, & magnesium carbonate.

Preservatives: Substances that commonly added to pharmaceutical products in order to prolong their shelf life. In concept, The Preservative system protect the pharmaceutical product against microbial proliferation but does not compromise product performance.

1/2/2016Prof. Dr. Nehal Afifi12 Ideal properties of preservatives: The preservative must exert a wide spectrum of antimicrobial activity at low inclusion levels( conc.) Preservative must maintain activity throughout product manufacture, shelf life and usage. Preservative must Not compromise the quality or performance of product, pack or delivery system. Preservative must Not adversely affect patient safety or tolerance of the product. Examples: Methyl & Ethyl Parabens, Propyl paraben, Benzoic acid & its salts, Sorbic acid & its salts.

1/2/2016Prof. Dr/ Nehal Afifi13Preservatives used in Pharmaceutical Preparations PreparationPreservativeConc. (% w.v)InjectionsPhenolCresolChlorocresol0.50.30.1Eye dropsChlorhexidine acetateBenzalkonium chloride0.010.01MixturesBenzoic acidMethyl parabenAlcohol0.10.112-20CreamsParabensChlorocresol0.1-0.20.10TabletsMethylparaben0.1

1/2/2016Prof. Dr. Nehal Afifi14 Humectants : Humectant attract & retains the moisture in the nearby air via absorption water vapor into and/or beneath organism/object's surface Humectants added to Ointments, Pastes, Creams , Emulsions, & Saturated sol. which defined as hydrophilic subs. added to aqueous phase to absorb water from atmosphere & prevent water loss from these dosage forms. Hum absorb water vapors from atmosphere till a certain degree of dilution attained Aqueous sol. reduce rate loss of moisture. Ideal properties of humectants : Must absorb moisture from atmosphere & retain the same under normal conditions of atmospheric humidity. should be colorless or not of too intense color. have good odor and taste. Nontoxic and nonirritant. Not be too costly. Noncorrosive to packaging materials Not solidify under normal conditions.

.

1/2/2016Prof. Dr. Nehal Afifi15 Classification of humectantswith examples : 3 types of humectants such as inorganic humectants, metal organic humectants and organic humectants. 1. Inorganic humectants: Calcium chloride is an example. has compatibility problems and corrosive in nature. Hence not frequently used in cosmetics. 2. Metal organic humectants: limited used in cosmetics because of compatibility problems, corrosive nature and pronounced taste. Example : sodium lactate. 3. Organic humectants: widely used in cosmetics. The most commonly used organic humectants areglycerol, ethylene glycol,polyethylene glycol (PEG), diethylene glycol, tri ethylene glycol,propylene glycol, dipropylene glycol, glycerin.

1/2/2016Prof. Dr. Nehal Afifi16 Antioxidants: Antioxidant is a molecule that inhibit oxidation of other mols. A chemical reaction that transfer electrons or hydrogen from a substance to oxidizing agent called Oxidation. Ideal Properties of Antioxidants: Effective at a low, nontoxic conc. Stable & effective under normal conditions of use, over a wide pH and temp. range. Soluble at the required conc. Compatible with a variety of drugs & pharmac. excipients. Free from objectionable odor, objectionable taste Colorless in both the original and oxidized form Nontoxic both internally and externally at the required conc. Unreactive ( not adsorb, penetrate, or interact) with containers or closures. Reasonable cost Eg: BHT( Butylated Hydroxy Toluene), Sodium metabisulfite, BHA( Butylated Hydroxy Anisol), and Ascorbic acid.

1/2/2016Prof. Dr. Nehal Afifi17 Sweetening Agents:S.A employed in liquid formulations designed for oral administration specifically to increase the palatability of the therapeutic agent. Example: Sucrouse, Saccarine, Aspertame, Sorbitol etc. Uses of sweetening agents: The main agents employed in oral preparations are sucrose, liquid glucose, glycerol, sorbitol, saccharin sodium & aspartame. Aspartame is an artificial sweetening agent. The Adverse use of artificial sweetening agents in formulations The use of sugars in oral formulations for children and patients with diabetes mellitus must be avoided.

1/2/2016Prof. Dr. Nehal Afifi18 Flavoring agents: Flavoring agents are added to increase patient acceptance. The four basic taste sensations are salty, sweet, bitter & sour Certain flavours should used to mask these specific taste sensations.Eg: Clove oil, citric & syrup, glycerin, rose oil, orange oil, menthol. Coloring agents: The ingredients that impart the preferred color to the pharmaceutical formulations are called coloring agents. There are 2 types of coloring agents1. Natural Coloring agents:2. Synthetic coloring agents.Eg.;1.White: Titanium dioxide. 2. Brown: caramel 3. Blue :Brilliant blue , Indigo carmine 4. Red :Amaranth Carmine. 5. Yellow: saffron .

1/2/2016Prof. Dr. Nehal Afifi19 Solvent: A solvent is a substance that can dissolve a solute (a chemically different liquid , solid or gas) resulting in solution. Solvent classification: Solvents can be broadly classified into 2 groups : Polar Solvents. Non polar Solvents. Polar solvents dissolve polar compounds best & non polar solvents dissolve non polar compounds best. Example & uses: The first choice for a Solvent is water in w. drug is freely soluble Water miscible solvent such as Chlordiazepoxide hydrochloride can used to improve solubility & stability Oils used as emulsion, IM. injections & liquid fill oral preparations Aqueous methanol used in HPLC & the standard solvent in sample extraction Other Acceptaple Non-aqueous solvents : glycerol ,propylene glycol, ethanol used generally for a lipophilic drug.

1/2/2016Prof. Dr. Nehal Afifi20 Co-solvent: Co-solvents are defined as water-miscible organic solvents that are used in liquid drug formulations to increase solubility of poorly water soluble substances or to enhance the chemical stability of a drug .Properties of co-solvent: Co-solvent should increase the solubility of a drug. An ideal co-solvent should possess values of dielectric constant between 25 and 80. The most widely used system that will cover this range is a water/ethanol blend. Should Not cause toxicity or irritancy when administrated for oral or parental uses. Eg.; sorbitol, glycerol, propylene glycol and syrup.

1/2/2016Prof. Dr. Nehal Afifi21 Buffering agents Buffering agents are materials which, when dissolved in solvent will enable the solution to resist any change in pH should an acid or alkali be added. The choice of suitable buffer depend on the pH & buffering capacity required. Features of buffering agent: Should have a low toxicity. Should be buffered at the range of 7.4 as pH of body is 7.4. Should be non-irritant. Examples: Most of buffering system based on Carbonate, citrates, gluconates ,lactates, phosphates, or tartrates .

1/2/2016Prof. Dr. Nehal Afifi22 Chelating agent: Chelating agent are molecules that are capable of forming complexes with the drug involving more than one bond or more ring in its structure . Example and uses : EDTA: ethylene diamine tetra acetate is used for the estimation of metals ions . EDTAH4: ethylene diamin tetra acetic acid is used for softening water. Calcium Disodium Edetate: used in treatment of heavy metal poisoning mostly caused by lead. Disodium Edetate: used in hypercalcemic states& in ttt of cardiac arrhythmias

1/2/2016Prof. Dr. Nehal Afifi23 Viscosity imparting agents : These agents used when it is desirable to increase or decrease the viscosity of a liquid either to serve as adjacent for palatability or to improve pour ability. They are also called thickening agents. Types: Viscosity imparting agents are 2 types Viscosity modifier: decrease the viscosity of a liquid to improve pour ability and make it more palatable. Viscosity enhancer: increase the viscosity of a liquid to improve pour ability and make it more palatable. Examples: Methylcellulose, Hydroxyethylcellulose, Hydroxypropylmethylcellulose , Polyvinyl alcohol Polyvinylpyrrolidon.

1/2/2016Prof. Dr. Nehal Afifi24 Surfactants: Surfactants are compounds that lower thesurface tension(or interfacial tension) between 2 liquids or between a liquid & a solid and increase solubility. Also known as surface active agents. Properties of surfactants : A surfactant must fulfill 2 structural requirements:A surfactant must contain a lipophilic region.A surfactant must contain a hydrophilic region.In a surfactant both hydrophilic & lipophilic region must balanced Types of surfactants : four types based on charge of the hydrophilic region1. Anionic surfactant ( the hydrophilic region negatively charged i.e. an anion)Eg.; Sodium lauryl sulphate : usedas anexcipienton some dissolvableaspirins.

1/2/2016Prof. Dr. Nehal Afifi25 2. Cationic surfactant ( hydrophilic region is positively charged i.e. a cation) Eg.; Cetyl trimethyl ammonium bromide ( cetrimide ) - is an effective antiseptic agent against bacteria & fungi.

3. Non-ionic surfactants : Eg.; Tween 80 ( polyoxyethylene sorbitol monooleate)- Polysorbate 80 is anexcipientthat is used to stabilize aqueous formulations of medications for Parenteral administration.

4. Amphoteric surfactant : Eg.; Lecithin- acts as a wetting, stabilizing agent and a choline enrichment carrier, helps in emulsifications and encapsulation, and is a good dispersing agent.

1/2/2016Prof. Dr. Nehal Afifi26References:1.Hand book of pharmaceutical excipients, Edition-Sixth, Edited by-Raymond Crowe Paul J Sheskey and Marian E Quinn, Publisher-Pharmaceutical Press.

2.Aultons Pharmaceutics The design and manufacture of medicines, Edition-Third, Edited by-Michael E.Aulton, Publisher-Elsevier.

3. Ansels Pharmaceutical Dosage Forms and Drug Delivery Systems, Edition- Ninth, Publisher-Lippincott Williams and Wilkins.

1/2/2016Prof. Dr. Nehal Afifi27

THANK YOU