factors affecting the selection of exepients


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factors affecting the selection of exepients

  1. 1. Factor Affecting The Selection Of Exepients. BYSNIGDHA SHUKLA M.PHARM (1ST YEAR)
  3. 3. INTRODUCTION: EXCIPIENTS An excipient is an inactive substance used as a carrier for the active ingredients of a medication. In many cases, an "active" substance (such as aspirin) may not be easily administered and absorbed by the human body Example: Binders, Disintegrants, Diluents, Flavo urs,
  4. 4. TYPES OF EXCIPIENTS Antiadhere USED to reduce the adhesion bet ween the powder (gran ules) Flavors used to mask unpleasant tasting active ingredients Binders Binders hold the ingredients in a tablet together Coatings tablet ingredients from deterioration by moisture Disintegrants dissolve when wet causing the tablet to break apart Colors improve the appearance of a formulation Glidants promote powder flow by reducing interparticle friction Lubricants Prevent ingredients from clumping together and from sticking to the tablet punches Fillers and diluents fill out the size of a tablet Preservatives PRESERVE THE FORMULATIO N
  5. 5. Excipients – an overview ● Drug products contain both drug substance (commonly referred to as active pharmaceutical ingredient or API) and excipients. ● 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 ● Excipients are sub-divided into various functional classifications, depending on the role that they are intended to play in the resultant formulation. Certain excipients can have different functional roles in different formulation types, ● e.g. lactose; widely used as: ● Furthermore, individual excipients can have different grades, types and sources depending on those different functional roles….
  6. 6. Diluents (Fillers) ● Bulking agent ◦ E.g. to make a tablet weight practical for the patient: minimum tablet weight is typically ~50mg. ● Compression aid ◦ Deforms and/or fragments readily to facilitate robust bonding in tablet compacts, e.g. microcrystalline cellulose. ● Good bulk powder flow….diluents have a strong influence ● Favoured combinations: Lactose is an excellent choice of filler in many respects but can exhibit poor flow characteristics
  7. 7. Disintegrants ● As an aid to de-aggregation of solid dosage forms. Disintegrants cause rapid break up (disintegration) of solid dosage forms upon exposure to moisture. ● Generally, disintegration is viewed as the first stage in the dissolution process, although dissolution does occur simultaneously with disintegration.
  8. 8. Binders ● Binders act as an adhesive to ‘bind together’ powders, granules and tablets to result in the necessary mechanical strength. ◦ Water is the most common granulating fluid, very occasionally in a cosolvent system with, e.g. ethanol. ● Examples: ◦ ◦ ◦ Dry binders: PVP Solution binders: Soluble in water/ethanol mix: Microcrystalline cellulose, cross-linked HPMC, PVP PVP
  9. 9. Lubricants Compression lubricants prevent adherence of granule/powder to punch die/faces and promote smooth ejection from the die after compaction: EX: Magnesium stearate is by far the most extensively used tableting lubricant There are alternatives, e.g. stearic acid, sodium stearyl fumarate, sodium behenate
  10. 10. Glidants Most commonly; colloidal silicon dioxide (traditionally, talc was used) ● Good bulk powder flowability is especially important during high speed processing ● Glidants improve flow by adhering to particles and so reducing inter-particulate friction ● Very low bulk density (0.03 – 0.04g/cm3)
  11. 11. Excipients For Solution/Suspension Products Again, excipients are sub-divided into various functional classifications, depending on the role that they play in the resultant formulation….
  12. 12. Solvents/Co-Solvents ● Water is the solvent most widely used as a vehicle due to: ◦ Lack of toxicity, physiological compatibility, and good solubilising power (high dielectric constant), but ⚫Likely to cause instability of hydrolytically unstable drugs ⚫Good vehicle for microbial growth ● ● Sorbitol, dextrose, etc. are often added as solubilisers, as well as base sweeteners Water-miscible co-solvents are used to: ◦ Enhance solubility, taste, anti-microbial effectiveness or stability ◦ Reduce dose volume (e.g. oral, injections) ◦ Examples: propylene glycol, glycerol, ethanol, low molecular weight PEGs ● Water-immiscible co-solvents, e.g. ◦ Emulsions / microemulsions using fractionated coconut oils
  13. 13. Buffering Agents ● Can be necessary to maintain pH of the formulation to: ◦ ◦ ◦ ◦ Ensure physiological compatibility Maintaining/optimising chemical stability Maintaining/optimising anti-microbial effectiveness Optimise solubility (or insolubility if taste is an issue)
  14. 14. Anti-microbial Preservatives Preservatives are used in ● multi-use cosmetic/pharmaceutical products ● Ideally targeted for microbial cells - showing no toxicity/irritancy towards mammalian cells ● There are a limited number of approved preservatives available for multi-use oral products, and options are even more limited for other routes of administration ● This restricted number can be further reduced by consideration of factors such as levels required (dose), pH-solubility profiles, API & excipient incompatibilities, adsorption, irritancy and toxicity.
  15. 15. Anti-Oxidants ● Used to control oxidation of: ◦ ◦ ◦ ◦ ● API Preservative, e.g. potassium sorbate Vehicle, e.g. oils or fats susceptible to β-oxidation (rancidification) Colourants (ageing discolouration) Sacrificial (more oxidisable than API, preservative, etc). Levels will reduce with time…. need to be monitored by specific assay ◦ Light exposure and metal ion impurities can accelerate oxidative degradation and hence depletion of antioxidant ● Need to assess regulatory acceptability (differs in different countries) ● Efficacy can be affected by: ◦ Compatibility with other excipients ◦ Partitioning into micelles (from surfactants)
  16. 16. Sweetening Agents Natural sweeteners ◦ Sucrose; ◦ Sorbitol Artificial sweeteners ◦ Can impart a bitter or metallic after-taste (hence used in combination with natural sweeteners), e.g. ⚫ Saccharin, and it’s salts ⚫ Aspartame ⚫ Acesulfame –K ⚫ Sucralose – excellent sweetness, non-cariogenic, low calorie, wide & growing regulatory acceptability but relatively expensive
  17. 17. Humectants ● Hygroscopic excipients used at ~5% in aqueous suspensions and emulsions for external application. ● Their function is to retard evaporation of aqueous vehicle of dosage form: ◦ To prevent drying of the product after application to the skin ◦ To prevent drying of product from the container after first opening ◦ To prevent cap-locking caused by condensation onto neck of container-closure of a container after first opening Examples include: ◦ propylene glycol ◦ glycerol ◦ PEG