MPharm Programme: Excipients PDF

MPharm Programme Excipients Dr Paul Carter MPharm  Excipients Drug often minor component of a dosage form (levothyroxine) presentina - quantity...

MPharm Programme Excipients Dr Paul Carter MPharm  Excipients Drug often minor component of a dosage form (levothyroxine) presentina - quantity Itma ~ I of in 1000 drug - 15mg Excipients are not therapeutically active, but are present for a purpose = bulk up drug the Care – excipients control behaviour of dosage form i.e. can affect bioavailability 2 measure of how much get into the blood/ rote absorption of e.g. tablets different / colors/size Facilitate manufacture/administration/identification Promote consistent drug release/bioavailability insoluble loyer around the ex 1 drug-control the Improve stability/protect drug against degradation time to release MPharm  Excipient – ideal properties Stable & reproducible No unintended interaction with drug - No chemd reaction Pharmacologically inert Give desired function Cost effective 11 Il Pharma grade – comply with BP, PhEur, or USP-NF (US pharmacopoeia) & manufactured under GMP. MPharm  Excipients - Role Aid in the processing of the drug delivery system during its manufacture ex1 mixing Protect, support, or enhance stability, bioavailability, or patient acceptability, ibuprofen ex) - - pink , sugar coat Assist in product identification, and enhance any attribute of the overall safety Assist in the effectiveness and/or delivery of the drug in use Assist in maintaining the integrity of the drug product during storage MPharm  Excipients - safety - affect bioavailability Late 1960s, phenytoin capsules. The calcium sulfate diluent ~ slowly release more was replaced by lactose giving an increase in the mean serum phenytoin concentration by a factor of 4.5. The drug had a narrow therapeutic index. Lactose is freely soluble in water, Iwhereas the calcium sulphate was slightly soluble. So, the calcium sulphate acted as a matrix and prolonged the release of the drug, whereas lactose gave an immediate and large release of phenytoin (above the toxic threshold). J Neurologic Sci. 1972, 16(4): p. 481-487 In 2007, pharmaceutical manufacturers in Panama used diethylene glycol, instead of glycerin, for the formulation of a ↓ cough syrup. Diethylene glycol (antifreeze) is nephrotoxic and um hepatotoxic. & ~ Glycerin Plethylene - 954B glycol MPharm  Excipients – adverse effects Excipients can occasionally be the cause of a medicine's side effects. A few examples: Excipient Linked with Glucose and sucrose Obesity, and tooth decay if taken orally Benzyl alcohol A gasping syndrome in neonates = babies Ethanol CNS effects Aspartame A source of phenylalanine in patients with phenylketonuria I can be toxic Polyoxyl castor oils Severe anaphylactoid reactions -alergic Propylene glycol CNS effects especially in neonates and children under 4 yrs - Colourants (e.g. tartrazine) Hypersensitivity and behavioural disturbances MPharm  Tablet compression/compaction need good flow · a consider packing · cavity ↓ powder - free flow - direct compression - don't have to granulate I less borous - H & in particles - particulate f ex) Van der elect Weds F > - tablet * MPharm  Tablet excipients e lactose picdclumphosphate sucruse dihydrate 17 glucose calcium carbonate Diluents or bulking agents = Filler Mannitol sorbitol cellulose added to make adequate sized tablet, handling eX) Lactose (α-lactose monohydrate) – pleasant taste good solubility/dissolution low hygroscopicity pick up 2 doesn't moisture Inert much consistent fairly property - Spray dried lactose – used for direct compression (DC) special/very ↳ porous Microcrystalline cellulose also good for DC - flow well + lactose too ! (mix tat) Mannitol for chewable tablets ~ tastier than lactose MPharm  Tablet excipients press meta - > stick ! post-mixing - 2) Lubricants mixing - put after it in the last Prevent powder/metal adherence – ensure smooth ejection from die CHECK disintegration coating Enhance flow properties > - > - effects EX intensely strength Magnesium stearate (up to 1 % w/w), hydrophobic HIGH contact angle - Prolong disintegration time, reduce drug dissolution, reduce tablet strength EX2) Sodium stearyl fumarate – hydrophilic I not as good as magnesium stearate MPharm  Tablet excipients * granules are pressed better than powders ! Binding agents only after granulation ! Adhesives to bind particles together during granulation Either added as dry powder during dry granulation or as a solution for wet granulation EX) Starch Polyvinylpyrrolidone (PVP) Glidants Improve flow of powders or granules Reduce interparticulate friction – smooth surface irregularities - rough/ surface irregular Colloidal silica - fill up the bits MPharm  Tablet excipients Disintegrating agents Cause tablet to disintegrate – increases surface area their volume [increase Swell in contact with water – burst open tablet e.g. starch, croscarmellose sodium (known as a ‘superdisintegrant’) Some work by capillary action, drawing liquid up through pores which disrupts bonds between particles e.g. pregelatinised starch Lyophilised tablets disintegrate with 5 s (orodispersible tablets), mainly 321 sucrose freezeldry > - very porous = How good Dyes and flavouring agents - - spray coating cellulose Coatings not too popular based ~ of Film or sugar coat ↳ layers longer sucrose disintegrate/ time to targeting 4 expensive - Enteric coatings e.g. cellulose acetate phthallate, or L polymers (Eudragits) gastro-resistant 2ccid-resistant ! pH4-dissolves (pH sensitive Polymers for M/R release e.g. HPMC (hydroxypropylmethyl cellulose), forming/slowly swell - xanthan gum => modified/controlled able to release MPharm  Excipients for Liquid Preparations Water Most widely used – physiologically non-toxic and compatible Good at dissolving ingredients BUT – supports microbiological growth and care with drugs prone to hydrolysis dissolve sm+ Helps q # Water miscible co-solvents Enhance solubility, taste and stability Propylene glycol, glycerol, ethanol MPharm  Excipients for Liquid Preparations 394 Buffers ex) anti-microbia - pH sensitive agents ? Control pH to enable physiological compatibility, microbial and chemical stability and solubility (or insolubility if taste is an issue) Antimicrobial agents Preservatives – prevent growth of opportunistic microbes (from excipients or externally introduced) Anti-oxidants ~ sacrifice to protect components of formulation Control oxidation of drug, preservative, other excipients Concentration decreases with time since they oxidise first MPharm  Excipients for Liquid Preparations Wetting agents if the drug hydrophobic is Decrease interfacial tension Surface active agents (e.g. Cetrimide, SLS), hydrophilic colloids (e.g cellulose derivatives, tragacanth – also act as suspending agents) Antifoaming agents (SHAKE - lot of form X) Simeticone Thickening agents ~editure Stoke's * law 4 viscosity, often thixotropic Stabilise suspensions – give high methylcellulose MPharm  Excipients for Liquid Preparations Sweetening agents Natural – sucrose Artificial – saccharin Flavouring agents Natural – peppermint Artificial – butterscotch Humectants ~ absorb moisture from atmosphere Hygroscopic excipients for external preparations (suspensions, emulsions) e.g. glycerol, PEGs Reduce evaporation of water/aqueous vehicle – prevents drying after application and during product life MPharm