Analysis of excipients of interest
- 1. EXCIPIENTS OF INTEREST Presented By M SREEKANTH 20031S0402 A SEMINAR ON
- 2. An Excipent is a pharmacologically inactive substance formulated alongside of the Active Pharmaceutical Ingredient (API) of Medication Drug products contain both drug substance (commonly referred to as active pharmaceutical ingredient or API) and excipients. Formulation of API with excipients is primarily to ensure an efficacious drug product with desired properties and a robust manufacturing process
- 3. The resultant biological, chemical and physical properties of the drug product are directly affected by the excipients chosen, their concentration and interactions with the API: •Consistency of drug release and bioavailability •Stability including protection from degradation •Ease of administration to the target patient population(s) by the intended route
- 4. •Excipients determine the bulk of the final product in dosage forms such as tablet, capsule, etc., the speed of disintegration, rate of dissolution,release of drug, protection against moisture, stability during storage, and compatibility . Ideal properties of excipient •No interaction with drug •Cost effective •Pharmacologically inert •Stable for handling •Feasible
- 5. Excipients are inactive ingredients used as carriers for the active ingredients in a pharmaceutical product. These may be classified into the following categories: •Antiadherents •Binders •Coatings •Disintegrants •Fillers and Diluents •Coloring Agents •Glidants & Emulsifiers •Lubricants •Preservatives •Sorbents & Sweeteners
- 6. DISINTEGRANTS AGENTS These are the substances Which are added to a tablet formulation to facilitate its breaking or disintegration when it contact in water in the GIT Such Tablet fragmentation Plays an important role in subsequent Dissolution of the tablet and which inturn governs the Bioavailability Of the Drug
- 7. MECHANISM They Draws Water into the Tablet This results in Swelling of the Tablet Then the Tablet Bursts A part
- 8. Examples;- 1)Starch and It's Derivatives 2) Cellulose & it's Derivatives 3)Clays 4)Alginates 5)PVP,Cross linked
- 9. STARCH & ITS DERIVATIVES Starch USP and various Starch Derivatives are the most commonly used Disintegrating Agents •Concentration range :5-10% •Low cost • Starch Derivatives and other modified Polymers can increase in volume by 200 -500% in presence of Water
- 10. STARCHES CONCENTRATION RANGE STARCH USP Carboxymethyl Starches Primogel Explotab Pregelatinised Starches 5-20% 1-8% 4% Optimum 5% Examples of Various Starches
- 11. CLAYS •Veegum HV & Bentonite are used Disintegrants • Concentration Range of 10% Demerits • Less Effective • Clay produce an off-white appearance
- 12. MICRO CRYSTALLINE CELLULOSE Trade Name : Avicel •It is a Direct Compression Material • Produces Cohesive impacts & also acts as Disintegranting agent Avicel grades -PH 101 ( powder) PH102 (granules)
- 13. Ac- Di-Sol •Ac-Di-Sol is internally cross linked form of sodium corboxymethyl cellulose •It is effective in low concentration levels •Cross linked PVP are also used as disintegranting agent
- 14. BINDERS Binders hold the ingredients in a tablet together. Binders ensure that tablets and granules can be formed by increasing cohesive state of the drug powder, with required mechanical strength. In other word according to WHO binders act as an adhesive to ‘bind together’ powders, granules and tablets to result in the necessary mechanical strength. Binders can be added to a powder in different ways: As a dry powder which is mixed with the other ingredients before wet agglomeration. During the agglomeration procedure the binder might thus dissolve partly or completely in the agglomeration liquid; As a solution which is used as agglomeration liquid during wet agglomeration. The binder is here often referred to as a solution binder.
- 15. Typical features of binders: A binder should be compatible with other products of formulation and add sufficient cohesion to the powders Binders are classified according to their application •Dry binders are added to the powder blend, either after a wet granulation step, or as part of a direct powder compression (DC) formula. e.g., Pregelatinised starch, cross- linked PVP, cellulose, methyl cellulose,PEG and •Solution binders are dissolved in a solvent (for example water or alcohol can be used in wet granulation processes). e.g., PVP, HPMC, gelatin, cellulose, cellulose derivatives, starch, sucrose and polyethylene glycol. • Soluble in water/ethanol Mix: PVP
- 16. •Acacia, Tragacanth, Gelatin, Sucrose, Starch paste are soluble in water and are not used in water sensitive drugs, while Na-alginate, Methyl cellulose dissolved in alcohol and PVP, Methyl cellulose drugs, while Na- alginate, Hydroxy Propyl cellulose dissolved both water and alcohol. • In case of water sensitive drugs first bender need to dissolve on alcohol and then other excipients and active ingredients are mixed with it.
- 17. Binders Used Concentration Required solvent Acacia 2-5% H2O Tragacanth 1-3% H2O Sucrose 2-20% H2O Gelatin 1-4% H2O Starch paste 1-4% H2O Na-alginate 3-5% Alcohol Methyl cellulose 1-4% Alcohol Pyrrolidone 2-5% H2O & Alcohol Ethyl cellulose 0.2-.0.5% H2O & Alcohol
- 18. EMULSIFIERS Emulsifying agents are those substances used in the emulsion to reduce the interfacial tension between the two phases i.e. aqueous phase and oily phase thus make them miscible with each other to form a stable emulsion.
- 19. Classification Emulsifying agents may be classified as follows: 1. Natural emulsifying agents from vegetable origin The natural emulsifying agents obtained from vegetable sources are carbohydrates which include gums and mucilaginous substances. They are anionic in nature and produce O/W emulsion. Examples are a. Acacia b. Tragacanth c. Agar d. Chondrus (Irish moss0 e. Pectin f. Starch. 2. Natural emulsifying agents from animal origin Examples are a. Gelatin b. Egg yolk c. Wool fat (Anhydrous lanolin)
- 20. 3. Semi-Synthetic polysaccharides Examples are a. Methyl Cellulose b. Sodium carboxymetjhyl cellulose 4. Synthetic emulsifying agents This group includes surface active agents.Examples are a. Anionic: Various alkali soaps, metallic soaps, sulphated alcohols and sulphonates. b. Cationic: Quaternary ammonium compounds. c. Non-ionic: Glyceryl esters e.g. Glyceryl monostearate. 5. Inorganic emulsifying agents Examples are a. Magnesium oxide b. Magnesium trisilicate c. Magnesium aluminium silicatwe d. Bentonite
- 21. The choice of emulsifying agents To get an emulsion of required properties, the emulsifying agent selected must have the following qualities .1. It should be capable of reducing the interfacial tension between the two immiscible liquids. 2. It should be capable of keeping the globules of dispersed liquid distributed indefinitely throughout the dispersion medium. 3. It should be non-toxic,4. The odour and taste should be compatible with the preparation. 5. It should be chemically compatible with other ingredients of the preparation.
- 22. VISCOSITY: Flow property of a simple liquid is expressed in terms of viscosity. Quantitatively, viscosity is an index of resistance of a liquid to flow. A fluid with large viscosity resists motion because its molecular makeup gives it a lot of internal friction. A fluid with low viscosity flows easily because its molecular makeup results in very little friction when it is in motion. VISCOSITY MODIFIERS
- 23. VISCOSITY PROMOTERS:These are substances ,which added to an aqueous mixture, increase its viscosity without substantially modifying its other properties , such as taste.They provide body, increase stability , and improvesuspension of added ingredients. It is desirable to increase the viscosity of liquid toprovide or to improve palatability or pourability •Polymers are used in suspensions, emulsions , and other dispersions ,primarily to minimize or control sedimentation
- 24. Advantages: •High viscosity inhibits the crystal growth. •High viscosity enhances the physical stability •High viscosity prevents the transformation of metastable crystal to stable crystal Disadvantages : •High viscosity hinders the re-dispersibility of the sediments. •High viscosity retards the absorption of the drug. •High viscosity creates problems in handling of the material during manufacturing.
- 25. IDEAL CHARACTERISTICS OF VISCOSITY PROMOTERS: Should produce a structured vehicle Should have high viscosity at negligible shear during storage and low viscosity at high shearing rates during pouring Should exhibit yield stress Should be compatible with other excipients Should be non-toxic Viscosity should not be altered by temperature or on ageing
- 26. CLASSIFICATION: Natural gums Acacia , Tragacanth Alginic acid Karaya , Guar gum etc., Cellulose derivatives Carboxy methyl cellulose Methyl cellulose Ethyl cellulose Hydroxy ethyl cellulose Hydroxy propyl methyl cellulose
- 27. Microcrystalline cellulose Chitosan Synthetic polymers Carbomer (poly acrylic acid) Polyvinyl pyrrolidone Polyvinyl alcohol Clays Magnesium aluminium silicate(veegum) Bentonite Attapulgite
- 28. 1) NATURAL GUMS Natural gums are polysaccharides of natural origin ,capable of causing a large viscosity increase in solution ,even at small concentrations. These polymers may be either non-ionic or anionic. Natural gums can be classified according to their origin 1. Natural gums obtained from seaweeds Agar, alginic acid, sodium alginate, carrageenan 2. Natural gums obtained from non-marine botanical sources Gum arabic (from the sap of acacia trees) Gum tragacanth(from the sap of astragalus shrubs) Karaya gum(from the sap of sterculia trees) Guar gum(from guar beans) Dammar gum (from the sap of dipterocarpaceae trees)
- 29. 3. Natural gums produced by bacterial fermentation Gellan gum Xanthan gum ALGINATES Anionic polysaccharide Derived from brown seaweed in the form of monovalent and divalent salts The most widely used one is sodium alginate Use :thickener and stabilizer
- 30. GUM ARABIC Anionic polysaccharide It is the dried exudate of trees of the genus acacia Unlike most natural gums,acacia exhibits very low solution viscosities At concentration under 40% ,solutions exhibits Newtonianflow;higher concentrations behave in a pseudo- plastic manner Use: suspending agent,emulsifier,adhesives and binders in tabletting
- 31. GUAR GUM Non-ionic polysaccharide derived from seeds It exhibits pseudo-plastic flow Disadvantage of these gels is the presence of insoluble plant residue Use: thickener , suspension stabilizer XANTHAN GUM Anionic polysaccharide Exhibits pseudo-plastic rheology Temperature has very little effect on the viscosity of xanthan solutions . This temperature independence of viscosity is unique to xanthan gum Use : thickener , suspension stabilizer , suspending agent
- 32. Applications of natural gums: Guar gum is a colon- specific drug delivery carrier is based on its degradation by colonic bacteria. Gum acacia used in confectionery industry and in baking industry. Gum tragacanth is still a preferred ingredient,particularly used in conjunction with gum acacia. Xanthan gum is a common suspending agent in suspension for reconstitution.
- 33. 2) CELLULOSE DERIVATIVES Cellulose is one of the most widely used starting material for manufacturing of modified natural polymers. Cellulose ethers with methyl substitution generally form a gel at a elevated temperatures. Gel formation is reversed when temperature is reduced. ETHYL CELLULOSE It is a non-ionic ether derivative of cellulose It is widely used as tablet binder ,thickening agent , coating material for tablets , microcapsules and microparticles. HYDROXY ETHYL CELLULOSE(HEC) It is a non-ionic cellulose ether Solutions of HEC exhibit pseudo-plastic flow
- 34. CARBOXY METHYL CELLULOSE(CMC) Sodium CMC is an anionic polymer and is available in 3 grades- Food , pharmaceutical and technical It is also available with a variety of molecular weights and degree of substitution. CMC is more resistant to microbial attack than most natural gums. The viscosity of CMC solution decreases reversibly with increasing temperature. The rheology of aqueous CMC solution depends on the degree substitution . Low substituted CMC products exhibit thixotropy; higher substitution leads to pseudo-plastic behaviour. Use : suspending agent, emulsion stabilizer
- 35. METHYL CELLULOSE & HYDROXY PROPYL METHYL CELLULOSE (HPMC) Both are interesting examples , as they exhibit a reversthermal gelation, gelling when heated and melting when cooled. These are the non-ionic cellulose ether derivatives. Rheology of these solutions is pseudo-plastic , and there is no yield point. Use : suspension stabilizer, thickener
- 36. Applications of cellulose derivatives: 1. Methyl cellulose: Used in pharmaceutical gels High viscosity grades are used in ophthalmic preparations Bulk forming laxative Lubricating jellies for surgical and medical procedures 2. HPMC: A 2% solution is commercially available as an ophthalmic surgical aid.
- 37. 3) MICROCRYSTALLINE CELLULOSE (MCC) Dispersions of MCC do not have viscosities that are significantly greater than that of water. However, combinations of CMC,MCor HPMC are used to thicken aqueous solutions. The colloidal dispersions of MCC blends exhibit thixotropy rheology , also exhibit a yield point. Viscosity is not affected by temperature It is used as stabilizer and thickener in aqueous systems Formulation of dry powder suspension with MCC:alginate complexes(0.5-10%w/w of total dry formulation)
- 38. 4) CHITOSAN Chitosan is a natural biopolymer derived from the outer shell of crustaceans. It is a weak cationic polysaccharide, biocompatible, biodegradable, non-toxic. Uses: As permeation enhancer and as mucoadhesive excipient It exhibits favourable biological behaviour , such as bioadhesion and permeability enhancing properties , which make it a unique material for the design of ocular drug delivery vehicles Enhanced bone formation by transforming growth factor and Used in tissue repair Cholesterol lowering effects
- 39. 5) SYNTHETIC POLYMERS Carbomer ( polyacrylic acid ) Solutions of carbomers are very pseudo-plastic and exhibit a yield value It is an excellent choice as a thickener in creams and lotions Carbomer 934P is the official name given to one member of a acrylic polymers . Manufactured under the trade name carbopol 934P, it is used as a thickening agent in a variety of pharmaceutical and cosmetic products. Polyvinyl pyrrolidone ( PVP ) Use : in ophthalmic preparations , serving as muco- mimetic agent
- 40. 6) CLAYS Magnesium aluminium silicate (veegum ) The gels are formed at about 5% concentration. They exhibit plastic flow It functions well as a suspending agents becauseit prevent caking without affecting pourability or spreadability of suspension Magnesium aluminium silicate dispersions are influenced by heat , and the viscosity of the dispersion increases onprolonged exposure to elevated temperatures.
- 41. CONCLUSION In pharmaceutical field , the viscosity promoters play a vital role , as they stabilize the disperse systems and also used in various dosage forms. Viscosity-inducing polymers should be used with caution . They are known to form complexes with a variety of organic and inorganic compounds.
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