Pharmaceutical Excipients.pdf

last topicfor exam 2 PHA 339 1  Understand different types of Pharmaceutical Excipients  Learn about different properties and function of pharmaceutical excipients  Structures of excipients will not be part of Exams. 2 Pharmaceutical Excipients anyingredientin dosageformotherthan the activeingred...

last topicfor exam 2 PHA 339 1  Understand different types of Pharmaceutical Excipients  Learn about different properties and function of pharmaceutical excipients  Structures of excipients will not be part of Exams. 2 Pharmaceutical Excipients anyingredientin dosageformotherthan the activeingredient s notherapeutic effects but still imporant Notabsorb moisturefrom environment Gaisintegrants diabeticpts vegetariancapsules 3 Pharmaceutical Excipients The pharmaceutical ingredients must be stabilized toward:  Environmental factors (air, water vapor, sunlight)  Interactions between different ingredients in the drug or different functionalities in the same molecule  Manufacturing stress (sterilization, compaction, etc.) microcrystalline cellulose 4 Pharmaceutical Excipients: Solids know thisslide tabs caps entericcoating cellulose acetatephthalate 5 Pharmaceutical Excipients: Liquids donot needto knowconc Ginemulsions tomake therm dynamically stable to maintainpH fordrugnot to degrade 6 Pharmaceutical Excipients: Liquids avoidmicrobial contamination Gpreventoxidation degradation metals ionsto prevent their oxidation insolutions suspensionsto improve pourability 7 Pharmaceutical Excipients: Semi-Solid lipidcomponents cocoabutter 8 Pharmaceutical Excipients: Semi-Solid inhibitmicrobialgrowth helpkeepdosageform intact 9 Adverse Reactions: Examples keep in mindpatientallergies3 diseasestates 10 Diluents: Lactose Lactose Milk Sugar  Disaccharide composed of one galactose and one glucose molecule  Lactose hydrous, lactose anhydrous, lactose monohydrate, or lactose spray-dried  Lactose Intolerance  Diluent: Microcrystalline Cellulose (MCC) binderlubricant Cellulose does not solubilizeeasily MCC is a purified, partially depolymerized cellulose  Most common source of pharmaceutical MCC is wood, in which cellulose chains are packed in layers held together by a cross-linking polymer (lignin) with strong hydrogen bonds.  Avicel (Brand Name)  Binders Starch (1,4-alpha-glycosidic linkages) Cellulose (1,4-beta-glycosidic linkages) move difficultbonds to break Polyethylene glycol (PEG) Gelatin ethyleneoxide chains linked partialhydrolysisof collagen 13 Binders Monomeric glucose exists as a mixture of a and banomers However, once the glucose is polymerized into starch or cellulose, the stereochemistry of the anomeric carbon is no longer in equilibrium. Starch (100 to 6000 glucose units) Starch has 1,4-alpha linkages Cellulose (1800 to 3000 glucose units) Cellulose has 1,4-beta linkages 14 Disintegrants helpbreakup releasedrug in GIT Carboxy Methyl Cellulose Calcium (Cellulose derivatives) Starch 1 5 Lubricant and Antiadherents Magnesium Stearate  Crystalline  Available as Monohydrate or Dihydrate or Mixtures canconvert hydrous anhydrous forms dif temps humidity Coatings Hydroxypropylmethylcellulose Gelatin  Most coated tablets are coated with hydroxypropylmethylcellulose (HPMC) and Capsules are coated with gelatin 1 7 Coating: Gelatin Gelatin is made by denaturing the triple helix of collagen, a protein which provides structural stability to bones and muscle. Gelatin is made by several processes which employ body parts from cattle, pigs, and horses and utilize chemical processes to achieve partial denaturation of the collagen 1 8 Enteric Coating Cellulose Acetate Phthalate (CAP)  Free carboxylic acid remains in polymer  This is an acidic functionality and is deprotonated (ionized) at basic pH drugpass unchanged into intestines then starts degrading 1 9 Enteric Coating Insoluble Water-soluble ionic form So, when [A-] = [HA], the pH = pKa. The pKa of carboxylic acids is in the range of 3-5. Thus, carboxylic acids are protonated (non-ionized) in the acidic environment of the stomach [pH = 2], but ionized in the more basic environment of the intestine [pH = 8]. 20 Surfactants  Highly lipophilic with HLB values range from 1 to 10, produced by transesterification of glycerol and triacylcerides (Fatty acids)  Polyoxyethylene sorbitan esters of fatty acids  Also, referred as Tween 20, 40, 60, 80 (What are these numbers?)  The number following the 'polysorbate' part is related to the type of fatty acid associated units part of the molecule. Monolaurate is indicated by 20, of repeatinggroups with the polyoxyethylene sorbitan monopalmitate is indicated by 40, monostearate by 60, and monooleate by 80. 21 Anti-Oxidants neutralizefreeradicals forstability Ascorbic acid Vit C Butylated hydroxyanisole Ascorbyl Palmitate Alpha-tocopherol it E 22 Buffering Agent Citric Acid Tartaric Acid Sodium Bicarbonate Lactic Acid 23 Preservatives stopor inhibit microorganismgrowth Parabens: Ex: Ethyl Paraben, Methyl Paraben Benzoic acid, Sodium Benzoate 24 Pharmaceutical Excipients: Drug Delivery Systems 25 useofsugarstomaintaingradient *Basic Principles and application of Pharmacy Practice, Dash et. al. self EmulsifyingDrugDeliverysystem 27 Polymer MW (g/mol) Physical state Tm (oC) Tg (oC) PVP 1,000,000 Amorphous – 174.2 HPMC 10,000–1,500,000 Amorphous – 145.2 EPO 100,000–250,000 Amorphous – 49.2 PEG 7000–9000 Crystalline 62 – PVP = polyvinylpyrrolidone, HPMC = hydroxypropyl methylcellulose, EPO = eudragit, PEG = polyethylene glycol 28 Biodegradable Polymers degrade itself in bodybe compatible so usually no need to removeimplant Natural polymers presentinnature  Fibrin  Collagen in nails hair  Chitosan from shellfish  Gelatin  Hyaluronic acid joint lubrication skin elasticity Synthetic polymers man made  PLA(Poly L-lactic acid), PGA (Poly glycolic acid) , PLGA (poly(lactic-co-glycolic acid) PCL(Polycaprolactone),  Polyorthoesters  Poly(dioxanone)  Poly(anhydrides)  Poly(trimethylene carbonate)  Polyphosphazenes Degradation Mechanism     Enzymatic degradation Hydrolysis Homogenous degradation Heterogenous degradation  Surface erosion (poly(ortho)esters and polyanhydrides)  Sample is eroded from the surface  Mass loss is faster than the ingress of water into the bulk  Bulk degradation (PLA,PGA,PLGA, PCL)  Degradation takes place throughout the whole of the sample  Ingress of water is faster than the rate of degradation Question What is the function of:  Lactose  Binder  Magnesium Stearate  Lubricant  Cellulose Acetate Phthalate  Enteric Coating  Ascorbic acid  Anti-Oxidant Review Questions1 Which excipient is commonly used as preservative? A) Ascorbic acid B) 0 Sodium Benzoic acid C) Cellulose acetate phthalate D) Sodium Bicarbonate 32 Review Questions 2 Which excipient is commonly used as an antioxidant? A) Ascorbic acid B) Magnesium stearate C) Cellulose acetate phthalate D) Lactose 33 Review Questions 3 Which is an example of hydrophilic or water-soluble base used as suppository base? A) Ascorbic acid B) Theobroma oil C) 0 Polyethylene glycol (PEG) D) Cocoa butter 34 Review Questions 4 Which is a synthetic biodegradable polymers? A) Gelatin B) Poly lactic-co-glycolic acid (PLGA) O C) Chitosan D) Hyaluronic acid 35 36 Gelatin Composition??  Amino acid composition of gelatin is: glycine 21%, proline 12%, hydroxyproline 12%, glutamic acid 10%, alanine 9%, arginine 8%, aspartic acid 6%, lysine 4%, serine 4%, leucine 3%, valine 2%, phenylalanine 2%, threonine 2%, isoleucine 1%, hydroxylysine 1%, methionine, and histidine