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  1. 1. Biopharmaceutics Classification System (BCS) 1
  2. 2. The (BCS) has been developed toprovide a scientific approach to allowfor the prediction of in vivopharmacokinetics of oral immediaterelease (IR) drug products byclassifying drug compounds based ontheir solubility related to dose andintestinal permeability in combinationwith the dissolution properties of thedosage form 2
  3. 3. The importance of drug dissolution in thegastrointestinal tract and permeabilityacross the gut wall barrier in the oralabsorption process has been well knownsince the 1960s, but the research carried outto constitute the BCS has provided newquantitative data of great importance formodern drug development especially withinthe area of drug permeability 3
  4. 4. According to the BCS, drug substances areclassified as follows:Class I - High Permeability, HighSolubilityClass II - High Permeability, LowSolubilityClass III - Low Permeability, HighSolubilityClass IV - Low Permeability, LowSolubility 4
  5. 5. The BCS is a scientific framework forclassifying drug substances based on theiraqueous solubility and intestinalpermeability. When combined with thedissolution of the drug product, the BCStakes into account three major factors thatgovern the rate and extent of drugabsorption from IR solid oral dosage forms:dissolution, solubility, and intestinalpermeability. 5
  6. 6. CLASS BOUNDARIESA drug substance is considered HIGHLYSOLUBLE when the highest dose strength is solublein < 250 ml water over a pH range of 1 to 7.5.A drug substance is considered HIGHLYPERMEABLE when the extent of absorption inhumans is determined to be > 90% of anadministered dose, based on mass-balance or incomparison to an intravenous reference dose.A drug product is considered to be RAPIDLYDISSOLVING when > 85% of the labeled amountof drug substance dissolves within 30 minutes usingUSP apparatus I or II in a volume of < 900 ml buffersolutions. 6
  7. 7. The benefits of knowing the BCS category of a compoundIt can save both time and money—if theimmediate -release, orally administered drugmeets specific criteria, the FDA will grant awaiver for expensive and time-consumingbio-equivalence studies.The aim of the BCS is to provide aregulatory tool for the replacement ofcertain BE studies by conductingaccurate in vitro dissolution tests. 7
  8. 8. Follow; The benefits of knowing the BCS category of your compoundThis step will certainly reduce timelinesin the drug development process, bothdirectly and indirectly, and reduceunnecessary drug exposure in healthyvolunteers, which is normally the studypopulation in BE studies.It has also been reported that theapplication of a BCS strategy in drugdevelopment will lead to significantdirect and indirect savings for 8
  9. 9. Follow; The benefits of knowing the BCS category of your compoundBCS has been developed primarily forregulatory applications, but it has alsoseveral other applications in both the pre-clinical and clinical drug developmentprocesses and has gained wide recognitionwithin the research-based industry 9
  10. 10. Combined with the dissolution, the BCStakes into account the three major factorsgoverning bioavailability viz. dissolution,solubility and permeability.This classification is associated with drugdissolution and absorption model, whichidentifies the key parameters controllingdrug absorption as a set of dimensionlessnumbers viz. 10
  11. 11. Key Parameters Controlling Drug Absorption Absorption number (An), defined as the ratio of the mean residence time to mean absorption time. Dissolution number (Dn), defined as the ratio of mean residence time to mean dissolution time. Dose number (D0), defined as the mass (Dose) divided by the product of (uptake volume (250 ml) and solubility of drug). D0 = Dose/(V.Cs) 11
  12. 12. Class I drugs exhibit a high absorptionnumber and a high dissolution number. Therate limiting step is drug dissolution. If dissolution is very rapid, then gastricemptying rate becomes the rate determiningstep.e.g. Metoprolol, Diltiazem, Verapamil,Propranolol. 12
  13. 13. Class II drugs have a high absorption number buta low dissolution number. In vivo drug dissolutionis then a rate limiting step for absorption except ata very high dose number. The absorption for classII drugs is usually slower than class I and occursover a longer period of time.In vitro- In vivo correlation (IVIVC) is usuallyexcepted for class I and class II drugs.e.g. Phenytoin, Danazol, Ketoconazole,Mefenamic acid, Nifedinpine. 13
  14. 14. For Class III drugs, permeability is ratelimiting step for drug absorption. Thesedrugs exhibit a high variation in the rate andextent of drug absorption.Since the dissolution is rapid, the variationis attributable to alteration of physiologyand membrane permeability rather than thedosage form factors.e.g. Cimetidine, Acyclovir, Neomycin B,Captopril. 14
  15. 15. Class IV drugs exhibit a lot ofproblems for effective oraladministration. Fortunately, extremeexamples of class IV compounds arethe exception rather than the rule andare rarely developed and reach themarket. Nevertheless a number of classIV drugs do exist. e.g. Taxol. 15
  16. 16. In vitro/in vivo correlation 16
  17. 17. Applications of BCS in oral drug delivery technologyOnce the solubility and permeabilitycharacteristics of the drug are known itbecomes an easy task for the researchscientist to decide upon which drug deliverytechnology to follow or develop. 17
  18. 18. Class I DrugsThe major challenge in development of drugdelivery system for class I drugs is to achieve atarget release profile associated with a particularpharmcokinetic and/or pharmacodynamic profile.Formulation approaches include both control ofrelease rate and certain physicochemicalproperties of drugs like pH-solubility profile ofdrug. 18
  19. 19. Class II DrugsThe systems that are developed for class IIdrugs are based on micronisation,lyophilization, addition of surfactants,formulation as emulsions andmicroemulsions systems, use of complexingagents like cyclodextrins. 19
  20. 20. Class III DrugsClass III drugs require the technologies thataddress to fundamental limitations ofabsolute or regional permeability. Peptidesand proteins constitute the part of class IIIand the technologies handling suchmaterials are on rise now days. 20
  21. 21. Class IV DrugsClass IV drugs present a major challengefor development of drug delivery systemand the route of choice for administeringsuch drugs is parenteral with theformulation containing solubility enhancers. 21