1. PHARMACEUTICS- IV (PHT 414 ) Dr. Shahid Jamil SALMAN BIN ABDUL AZIZ UNIVERSITY COLLEGE OF PHARMACY L9-10110/9/2015 Factors Affecting Drug Absorption (Dosage form factor)

2. Pharmaceutical Excipients Excipients are add to ensure the acceptability, physiochemical stability, bioavailability and functionability of the drug product. More the number of excipients in a dosage form, the more complex and greater the absorption and bioavailability problems. 10/9/20152L9-10

3. Commonly used excipients: DiluentsBindersDisintegrantsLubricantsCoatings Suspending agents SurfactantsBuffers Complexing agents ColorantsSweeteners. 10/9/20153L9-10

4. Vehicle : The three categories of vehicles in use are:. Aqueous vehicles – water, syrup. Non aqueous water miscible vehicles – propylene glycol, glycerol. Non aqueous water immiscible vehicles – vegetable oils Rate of absorption – depends on its miscibility with biological fluid. Miscible vehicles (aqueous or water miscible vehicle) causes rapid absorption e.g. propylene glycol. Miscible vehicles (aqueous or water miscible vehicle) causes rapid absorption e.g. propylene glycol. Immiscible vehicles – Absorption depends on its partitioning from oil phase to aqueous body fluid. 10/9/20154L9-10

5. Diluents (Fillers): Hydrophilic diluents – Imparts Absorption Hydrophobic diluents – Retards Absorption Also, there is a drug- diluent interaction, forming insoluble complex and retards the absorption. E.g. Tetracycline-DCP(dicalcium phosphate) Binders & granulating agent : Hydrophilic binders – Imparts hydrophilic properties to the granule surface – gives better dissolution properties of the poorly wettable drugs. E.g. Starch, Gelatin. But more amount of binder increases the hardness of the tablet and retards the absorption rate. 10/9/20155L9-10

6. Disintegrants : Mostly hydrophilic in nature. Decrease in amount of disintegrants – significantly lowers B.A. Suspending agents/viscosity agent : Stabilized the solid drug particles and thus affect drug absorption. Macromolecular gum forms un-absorbable complex with drug e.g. Na CMC. forms a poorly soluble complex with amphetamine. Viscosity imparters – act as a mechanical barrier to diffusion of drug from its dosage form and retard GI transit of drug. Lubricants: These agents are added to tablet formulations to aid flow of granules Commonly hydrophobic in nature – therefore inhibits penetration of water into tablet and thus dissolution and disintegration. 10/9/20156L9-10

7. Buffers : Buffers are sometimes useful in creating the right atmosphere for drug dissolution as was observed for buffered aspirin tablets However, certain buffer systems containing potassium cations inhibit the drug absorption as seen with Vitamin B 12 and sulfanilamide. Colourants: Even a low concentration of water soluble dye can have an inhibitory effect on dissolution rate of several crystalline drugs. The dye molecules get absorbed onto the crystal faces and inhibit the drug dissolution. For example: Brilliant blue retards dissolution of sulfathiazole. 10/9/20157L9-10

8. Surfactants : May enhance or retards drug absorption by interacting with drug or membrane or both. Physiologic surfactants – bile salts – promotes absorption – e.g. Griseofulvin, steroids Coating : In general, deleterious effects of various coatings on the drug dissolution from a tablet dosage form are in the following order. Enteric coat > sugar coat > non-enteric coat. The dissolution profile of certain coating materials change on aging; e.g. shellac coated tablets, on prolonged storage, dissolve more slowly in the intestine. This can be however, be prevented by incorporating little PVP in the coating formulation. 10/9/20158L9-10

9. Product Age and Storage Condition A number of changes, especially in the physiochemical properties of a drug in a dosage from, can result due to aging and alteration in storage conditions which can adversely affect bioavailability. For example: Precipitation of the drug in solution Hardening of tablet Change in particle size of suspension. Change in particle size of suspension. 10/9/20159L9-10

10. Rapid disintegration is important to have a rapid absorption so lower disintegration time is required. Rapid disintegration is important to have a rapid absorption so lower disintegration time is required. Disintegration time of tablet is directly proportional to –amount of binder and compression force. Disintegration time of tablet is directly proportional to –amount of binder and compression force. It is important to note that in vitro disintegration test gives no means of a guarantee of drugs B.A. because if the disintegrated drug particles do not dissolve then absorption is not possible. It is important to note that in vitro disintegration test gives no means of a guarantee of drugs B.A. because if the disintegrated drug particles do not dissolve then absorption is not possible. 10/9/201510L9-10 DISINTEGRATION TIME :

11. It is provided to determine the compliance with the limit on disintegration stated in the individual monograph. It is provided to determine the compliance with the limit on disintegration stated in the individual monograph. Formulation tested are Formulation tested are un coated tab, plain coated, enteric coated, buccal, sub lingual, hard gelatin capsule un coated tab, plain coated, enteric coated, buccal, sub lingual, hard gelatin capsule For un coated tab and capsules the time is 30 mins. where as for coated tab it is 2 hrs. For un coated tab and capsules the time is 30 mins. where as for coated tab it is 2 hrs. Disintegration can be aided by incorporating disintegrants in suitable amount during formulation. Disintegration can be aided by incorporating disintegrants in suitable amount during formulation. 10/9/201511 DISINTEGRATION TESTS L9-10

12. Dissolution time: Dissolution is a process in which a solid substance solubilise in a given solvent i.e. … mass transfer from the solid surface to the liquid phase. Dissolution time: Dissolution is a process in which a solid substance solubilise in a given solvent i.e. … mass transfer from the solid surface to the liquid phase. Dissolution time is also an important factor which affect the drug absorption. Dissolution time is also an important factor which affect the drug absorption. 10/9/201512L9-10 DISSOLUTION TIME:

13. The development of this test predicts the drug absorption. The development of this test predicts the drug absorption. It shows close relation b/w drug absorption and dissolution rather than disintegration. It shows close relation b/w drug absorption and dissolution rather than disintegration. By using USP apparatus By using USP apparatus type1- basket method type1- basket method type2- paddle method type2- paddle method Basket method- the basket containing tab and capsules are immersed in the dissolution fluid and rotated. Basket method- the basket containing tab and capsules are immersed in the dissolution fluid and rotated. Paddle method-the dosage form is placed directly in the dissolution medium and paddle is rotated. Paddle method-the dosage form is placed directly in the dissolution medium and paddle is rotated. Fluids may be water, HCL, buffer maintained at 37 0 c. Fluids may be water, HCL, buffer maintained at 37 0 c. The samples are removed at desired interval and assayed for drug content. The samples are removed at desired interval and assayed for drug content. 10/9/201513 DISSOLUTION L9-10

14. Thank you E-mail: shahidjamil07@gmail.com 10/9/201514L9-10