BCS classification (SHETTY CHETHAN).pptx

BCS classification

1. THE BIOPHARMACEUTICS CLASSIFICATION SYSTEM (BCS) PRESENTED BY Shetty Chetan Kumar M.PHARM – I YEAR DEPT. OF PHARMACEUTICS MALLIGE COLLEGE OF PHARMACY SUBMITTED TO: Prof .H.S Keerthy DEPT. OF PHARMACEUTICS MALLIGE COLLEGE OF PHARMACY

2. contents Introduction Biopharmaceutical Classification System Objective BCS Classifications Factor affecting BCS Application References 2

3. introduction The Biopharmaceutical Classification System was first developed in 1995, by Amidon et al & his colleagues. Definition: "The Biopharmaceutical Classification System is a scientific framework for classifying a drug substance based on its aqueous solubility & intestinal permeability & dissolution rate". To save time fast screening is required so drug substances are classified on basis of solubility and permeability. This classification is called Biopharmaceutical Classification System . The BCS is a scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability. 3

4. When combined with the dissolution of the drug product, the BCS takes into account three major factors that govern the rate and extent of drug absorption from IR solid oral dosage forms. These factors are dissolution, solubility and intestinal permeability. Based on the intestinal permeability and solubility of drugs, Amidon et al developed Biopharmaceutics Classification System (BCS) which classifies the drugs into one of the 4 groups as 4

5. CLASS SOLUBILITY PERMEABILITY ABSORPTION PATTERN RATE LIMITING STEP IN ABSORPTION EXAMPLE I HIGH HIGH WELL ABSORBED GASTRIC EMPTYING DILTIAZEM II LOW HIGH VARIABLE DISSOLUTION NIFEDIPINE III HIGH LOW VARIABLE PERMEABILITY INSULIN IV LOW LOW CASE BY CASE CASE BY CASE TAXOL 5

6. Biopharmaceutical Classification System objectives To guide decisions with respect to in-vivo and in-vitro correlations and the need for bioequivalence studies . To provide a useful framework to identify appropriate dosage form designs that are aimed at overcoming absorption barriers posed by solubility and permeability related challenges . 6

7. BCS Class I: High Solubility and High Permeability Compounds belonging to this class are normally expected to dissolve quickly in gastric and intestinal fluids, and readily cross the intestinal wall through passive diffusion. BCS Class I are unlikely to show bioavailability or bioequivalence issues. Although class I compounds are expected to have excellent oral absorption, given their high solubility and high permeability, additional absorption barriers may exist . For example, luminal complexation and degradation can significantly limit the amount of drug available for absorption. 7

8. Therefore, for BCS class I drugs, in vitro dissolution studies are thought to provide sufficient information to assure in vivo product performance making full in vivo bioavailability/ bioequivalence studies unnecessary. Even after the drug crosses the intestinal membrane, it may be metabolized within the enterocytes/hepatocytes and/or pumped out of the cells due to efflux mechanisms . 8

9. BCS Class II: Poor Solubility and High Permeability By definition, poor solubility and/or slow dissolution are the rate-limiting steps for oral absorption of BCS class II compounds For compounds with a very large dose-to solubility ratio, poor solubility is likely to be the rate-limiting step for absorption. In other words, the compounds may dissolve quickly enough to reach their equilibrium solubility, but the solubility is too low to establish a wide enough concentration gradient to drive passive diffusion 9

10. Formulations designed to overcome solubility or dissolution rate problems: Salt formation Particle size reduction Metastable forms Solid dispersion Complexation Lipid based formulations Precipitation inhibitors 10

11. BCS Class III: High Solubility and Low Permeability Since passive diffusion is the rate-limiting step for oral absorption of BCS class III compounds, the most effective way to improve absorption and bioavailability of this class of compounds is to increase the membrane permeability Approaches to improve permeability: Prodrugs Permeation enhancers 11

12. BCS Class IV: Low Solubility and Low Permeability Class IV compounds exhibit both poor solubility and poor permeability, and they pose tremendous challenges to formulation development As a result, a substantial investment in dosage form development with no guarantee of success should be expected A combination of class II and class III technologies could be used to formulate class IV compounds, although the success rate is not expected to be high 12

13. CLASS SOLUBILITY PERMEABILITY COMMENTS Class I High High Drug dissolves rapidly and is well absorbed. Bioavailability problem is not expected for IR drug approaches. Class II Low High Drug is dissolution limited and well absorbed. Bioavailability is controlled by the dosage form and the rate of release of the drug substance. Class III High Low Drug is permeability limited. Bioavailability may be incomplete if drug is not dissolved or released within the absorption window. Class IV Low Low Difficulty in formulating a drug product that will deliver a consistent drug bioavailability. An alternative route of administration may be needed. 14

14. FACTOR AFFECTING ON BCS The Biopharmaceutical Classification System has been developed to provide a scientific approach to allow for to prediction in-vivo pharmacokinetics of oral immediate release (IR) drug product by classifying drug compound based on their : SOLUBILITY PERMEABILITY DISSOLUTION 15

15. solubility An objective of the BCS approach is to determine the equilibrium solubility of a drug under approximate physiologic conditions. For this purpose, determination of pH–solubility profiles over a pH range of 1–8 is suggested. The solubility class is determined by calculating what volume of an aqueous medium is sufficient to dissolve the highest anticipated dose strength. A drug substance is considered highly soluble when the highest dose strength is soluble in 250 mL or less of aqueous medium over the pH range 1–8. 16

16. permeability Study of extent of absorption in humans and intestinal permeability methods can be used in determining the permeability class of a drug. To be classified as highly permeable, a test drug should have an extent of absorption >90% in humans. Supportive information on permeability characteristics of the drug substance should also be derived from its physical–chemical properties ( eg , octanol: water partition coefficient). 17

17. Some methods to determine the permeability of a drug from the gastrointestinal tract include (1) in vitro permeation experiments using excised human or animal intestinal tissues (2 ) in vitro permeation experiments across a monolayer of cultured human intestinal cells. (3) in vivo intestinal perfusion studies in humans; (4) in vivo or in situ intestinal perfusion studies in animals; When using these methods, the experimental permeability data should correlate with the known extent-of-absorption data in humans. After oral drug administration, in vivo permeability can be affected by the effects of efflux and absorptive transporters in the gastrointestinal tract, food and possibly by the various excipients present in the formulation 18

18. DISSOLUTION The dissolution class is based on the in vitro dissolution rate of an IR drug product under specified test conditions and is intended to indicate rapid in vivo dissolution in relation to the average rate of gastric emptying in humans under fasting conditions. An IR drug product is considered rapidly dissolving when not less than 85% of the label amount of drug substance dissolves within 30 minutes using USP Apparatus I at 100 rpm or Apparatus II at 50 rpm in a volume of 900 mL or less in each of the following media: (1) acidic media such as 0.1 N HCl or simulated gastric fluid USP without enzymes (2 ) pH 4.5 buffer and (3) pH 6.8 buffer or simulated intestinal fluid USP without enzymes. The FDA is in the process of revising the BCS guidance to permit biowaivers for generic formulations of Class 3 drugs. 19

19. APPLICATION To predict in vivo performance of drug product using solubility and permeability measurements. Aid in earliest stages of drug discovery research. To use in biowaiver considerations. For research scientist to decide upon which drug delivery technology to follow or develop. Also for the regulation of bioequivalence of the drug product during scale up and post approval. 20

20. QUESTIONS Explain Biopharmaceutics classification system in detail ? 21

21. THANK YOU 22