2.Sagar Goda Biological classification system (BCS); its significance on dissolution study
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The Biopharmaceutics Classification System (BCS) classifies drug substances into four classes based on solubility and permeability, aiming to streamline drug development and reduce testing requirements. It is widely utilized in areas such as drug formulation, approval processes, and optimizing new chemical entities while allowing biowaivers for class I drugs under specific conditions. Additionally, recent modifications to the classification have introduced more categories based on detailed solubility and permeability assessments to improve prediction of drug absorption.
2.Sagar Goda Biological classification system (BCS); its significance on dissolution study
- 1. BIOPHARMACEUTICS CLASSIFICATION SYSTEM (BCS); ITS SIGNIFICANCE ON DISSOLUTION STUDY & APPLICATION IN DOSAGE FORM DEVELOPMENT 1 Guided By:- Dr. R. D. PARMAR DEPARTMENT OF PHARMACEUTICS B.K.M.G.P.C. RAJKOT-360005 PReSeNTed By:- SAGAR Y. GODA M.PHARM.: - I ROLL NO: 03 EN NO: 162120808005 (2016-17)
- 2. • Introduction to BCS • Objective of the BCS • Classification of drugs as per BCS • Class boundaries • Applications of BCS • Exception for BCS • Extension to BCS • Conclusion • Reference 2/18
- 3. The Biopharmaceutics Classification System (BCS) was proposed in 1995 by Amidon . It is a scientific framework which divides APIs into four groups, according to their solubility and permeability properties. This approach is meant to reduce unnecessary in vivo bioequivalence studies however, is restricted to non- critical drug substances in terms of solubility, permeability, and therapeutic range, and to non-critical pharmaceutical forms. 3/18
- 4. To improve the efficiency of the drug development and review process by recommending a strategy for identifying expendable clinical bioequivalence test. To recommend a class of immediate-release (IR) solid oral dosage forms for which bioequivalence may be assessed based on in vitro dissolution tests. To recommend methods for classification according to dosage form dissolution along with the solubility– permeability characteristics of the drug product. 4/18
- 5. According to the BCS, drug substances are classified as follows 5/18 Class 1: High Solubility – High Permeability Class 2: Low Solubility - High Permeability Class 3: High Solubility - Low Permeability Class 4: Low Solubility - Low Permeability
- 6. • Class I - High Solubility, High Permeability – Example: metoprolol – Those compounds are well absorbed and their absorption rate is usually higher than excretion. • Class II – Low Solubility, High Permeability – Example: Glibenclamide – The bioavailability of those products is limited by their solvation rate. A correlation between the in vivo bioavailability and the in vitro solvation can be found. • Class III – High Solubility, Low Permeability – Example: Cimetidine – The absorption is limited by the permeation rate but the drug is solvated very fast. If the formulation does not change the permeability or gastro-intestinal duration time, then class I criteria can be applied. • Class IV - Low Solubility, Low Permeability – Example: Hydrochlorothiazide – Those compounds have a poor bioavailability. Usually they are not well absorbed over the intestinal mucosa and a high variability is expected. 6/18
- 7. HIGHLY SOLUBLE: When the highest dose strength is soluble in < 250 ml water over a pH range of 1 to 7.5. HIGHLY PERMEABLE: When the extent of absorption in humans is determined to be > 90% of an administered dose RAPIDLY DISSOLVING: When no less than 85% of the labeled amount of the drug substance dissolves within 30 minutes, using U.S. Pharmacopeias (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) 0.1 N HCl or Simulated Gastric Fluid USP without enzymes (2) a pH 4.5 buffer; (3) a pH 6.8 buffer or Simulated Intestinal Fluid USP without enzymes 7/18
- 8. • BCS is widely used in design and development of innovation drugs, new dosage forms (Permeability amplifiers), in clinical pharmacology (drug- drug, drug-food interaction) and also by regulation agencies of several countries as the scientific approach, for testing of waivers on bioavailability. Given below the application of BCS in different fields: • 1. Application of BCS in Oral Drug Delivery Technology Once the solubility and permeability characteristics of the drug are known it becomes an easy task for the research scientist to decide upon which drug delivery technology to follow or develop. Class-I Drugs • The major challenge in development of drug delivery system for class I drugs is to achieve a target release profile associated with a particular pharmacokinetic and/or pharmacodynamics profile. Formulation approaches include both control of release rate and certain physicochemical properties of drugs like pH-solubility profile of drug. 8/18
- 9. • Class-II Drugs The systems that are developed for class II drugs are based on micronisation, lyophilization, and addition of surfactants, formulation as emulsions and microemulsions systems and use of complexing agents like cyclodextrins. • Class-III Drugs Class III drugs require the technologies that address to fundamental limitations of absolute or regional permeability. Peptides and proteins constitute the part of class III and the technologies handling such materials are on rise now days. • Class-IV Drugs Class IV drugs present a major challenge for development of drug delivery system and the route of choice for administering such drugs is parenteral with the formulation containing solubility enhancers. 9/18
- 10. BCS ClaSS Formulation High solubility high permeability Low solubility high permeability High solubility low permeability Low solubility low permeability Simple capsule or tablet Micronized API and surfactant Nano-particle technology Solid dispersion Coating technology Liquid or semisolid filled capsule Melt granulation/extrusion Simple capsule or tablet Absorption enhancers Combination of BCS 2 and absorption enhancers 10/18
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- 12. 2. Application of BCS in New Drug Application (NDA) and Abbreviated New Drug Application (ANDA) The principles of the BCS classification system can be applied to NDA and ANDA approvals as well as to scale-up and post approval changes in drug manufacturing. A waiver of In-vivo Bioavailability and Bioequivalence studies based on the BCS classification can therefore save pharmaceutical companies a significant amount of development time and reduce development costs. 3. Application of BCS in optimization of new chemical entity The pharmacokinetic idea of new chemical entity which is already synthesized or identified and has therapeutic value but still under investigation for formulation development and final approval can be provided by BCS. The BCS provide an opportunity to the synthetic chemist to manipulate in the chemical structure in the chemical entity in order to optimize the physicochemical properties of lead molecule for desired delivery and targeting through High Throughput Pharmaceutics (HTP).( Jorgensen W. L. et al, 2002 and Lobel L. M. et al, 2003) 12/18
- 13. BIOWAIVERS In simple word exemption of clinical bioequivalence study of drug product. BCS gives biowaivers for only class-I drugs. Following criteria are recommended for justifying the request for a waiver of in-vivo bio-studies. 1. Highly soluble and highly permeable (class I drugs). 2. An immediate release (IR) drug product. 3. Dissolution should be greater than 85% in 30 minutes in the 3 recommended dissolution media 4. The drug should not be a narrow therapeutic index drug. 5. Excipient used should have been previously used in a FDA approved IR solid dosage forms. The quantity of excipient in IR product should be consistent with their intended function. 6. The drug must be stable in gastro intestinal tract 7. Product is designed not to be absorbed in oral cavity. 13/18
- 14. BCS-based biowaivers are not applicable for the following: 1. Narrow Therapeutic Range Drugs This guidance defines narrow therapeutic range drug products as those containing certain drug substances that are subject to therapeutic drug concentration or pharmacodynamic monitoring, and /or where product labeling indicates a narrow therapeutic range designation. Examples include digoxin, lithium, phenytoin, theophylline, and warfarin. Because not all drugs subject to therapeutic drug concentration or pharmacodynamic monitoring are narrow therapeutic range drugs, sponsors should contact the appropriate review division to determine whether a drug should be considered to have a narrow therapeutic range. 14/18
- 15. 2. Products Designed to be absorbed in the Oral Cavity A request for a waiver of in vivo BA/BE studies based on the BCS is not appropriate for dosage forms intended for absorption in the oral cavity (e.g. sublingual or buccal tablets). 15/18
- 16. • Bergstrom et al. in 2003 devised a modified Biopharmaceutical Classification System, in which they categorized the drugs into six classes based on the solubility and permeability. The solubility was classified as "high" or "low" and the permeability was allotted as "low", "intermediate," or "high". • This new classification was developed based on the calculated surface area descriptors on the one hand and solubility and permeability on the other. Surface areas related to the nonpolar part of the molecule resulted in good predictions of permeability. It was tentatively concluded that these models would be useful for early indication with regard to the absorption profiles of the compound during the early stages of drug discovery so that the necessary modifications can be made to optimize the pharmacokinetic parameters. 16/18
- 17. Poor solubility and poor permeability account for many pharmacokinetic failures and about thirty percent of drug molecules are rejected due to pharmacokinetic failures. When poor pharmaceutical properties are discovered in development, the cost of bringing a potent, but poorly absorbable molecule to the product stage by formulation can become very high. Fast and reliable in vitro prediction strategies are needed to filter out problematic molecules at the earliest stage of discovery. This communication will consider recent developments in physiochemical profiles used to identify molecules with physical properties related to good oral absorption. FDA's biopharmaceutical classification system (BCS) is an attempt to rationalize the critical components related to oral absorption and utilization of these principles for selection of a suitable technology to serve the interests of the early stages of drug discovery. 17/18
- 18. 1. Biopharmaceutics & Pharmacokinetics by D.M.Bramankar 2.Journal of Current Pharmaceutical Research 2011; 5 (1): 28-31 3. International Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304 Vol.2, No.3, pp 1681-1690, July-Sept 2010 4. Guidance for Industry Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System ,U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER) August 2000 5. Guidance for Industry “Waiver of In vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on BCS” 18/18
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