Biopharmaceutics Classification System

CLASS 1 (amphiphilic) 3 diltiazem antipyrine labetolol glucose captopril L-dopa enalapril metoprolol propranolol phenylalanine 

CLASS 3 (hydrophilic) c famotidine atenolol cimetidine acyclovir ranitidine nadolol hydrochlorothiazide 

CLASS 2 (lipophilic) flurbiprofen ketoprofen naproxen desipramine diclofenac itraconazole piroxicam carbamazepine phenytoin verapamil  

The rapid dissolution class boundary is defined in terms of the in vitro dissolution being greater than 85% in 30 min in 900 mL aqueous media at pH 1, 4.5, and 6.8, using USP Apparatus I (100 rpm) or Apparatus II [50 rpm (revolutions/min)] [104]. A similar guideline has been introduced in the European Union [105]. Examples of molecules from the various four classes are presented in Fig. 2.9 [102,104]. 

The method of choice for the measurement of ionization constants is potentio-metry [35,112-119]. Special circumstances warrant the determination of the pKa by UV spectrophotometry [120-143], capillary electrophoresis (CE) [144-147], and a chromatographic technique [148]. In principle, UV and CE methods are more sensitive and less sample-demanding than is the pH-metric method. That not withstanding, the latter method is preferred because it is so much better developed, 

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Fig. 12 Illustration of the Biopharmaceutical Classification System (BCS), which classifies drug absorption potential on the basis of aqueous solubility or membrane permeability. (Copyright 2000 Saguaro Technical Press, Inc., used with permission.)...

Bioavailability depends not only on having the drug in solution, but also on the drug s permeability. A jejunal permeability of at least 2-4 x 10 4cm/s, measured in human subjects by intubation, is considered high [97]. For many drugs and other substances, this permeability corresponds to a fraction absorbed of 90% or better. Amidon et al. [97] thus proposed a Biopharmaceutics Classification System (BCS) for drugs based on the above definitions of these two parameters. Table 3 defines the BCS and includes some drugs representative of each class. 

Waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on a biopharmaceutics classification system. Center for Drug Evaluation and Research, Food and Drug Administration, issued 8/2000, posted 8/31/2000. http //www.fda.gov/cder/guidance/ index, htm... 

Figure 2.9 Biopharmaceutics classification system [101-110]. Examples are from Refs. 102 and 104. [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

FDA Guidance for Industry Waiver of in vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Containing Certain Active Moieties/ Active Ingredients Based on a Biopharmaceutics Classification System, CDER-GUID 2062dft.wpd Draft, Jan. 1999. 

Lentz, K. A. Hayashi, J. Lucisano, L. J. Polli, J. E., Development of a more rapid, reduced serum culture system for Caco-2 monolayers and application to the biopharmaceutics classification system, Int. J. Pharm. 200, 41-51 (2000). 

AC ADME ANS AUC BA/BE BBB BBM BBLM BCS BLM BSA CE CHO CMC CPC CPZ CTAB CV DA DOPC DPPC DPPH aminocoumarin absorption, distribution, metabolism, excretion anilinonaphthalenesulfonic acid area under the curve bioavailability-bioequivalence blood-brain barrier brush-border membrane brush-border lipid membrane biopharmaceutics classification system black lipid membrane bovine serum albumin capillary electrophoresis caroboxaldehyde critical micelle concentration centrifugal partition chromatography chlorpromazine cetyltrimethylammonium bromide cyclic votammetry dodecylcarboxylic acid dioleylphosphatidylcholine dipalmitoylphosphatidylcholine diphenylpicrylhydrazyl... 

Fig. 7.5. The Biopharmaceutics Classification System (BCS) provides a scientific basis for predicting intestinal drug absorption and for identifying the rate-limiting step based on primary biopharmaceutical properties such as solubility and effective intestinal permeability (Pefr). BCS serves as a product control instrument. The BCS divides drugs into four different classes based on their solubility and...

Based on their solubility and intestinal permeability characteristics, drugs have been classified into one of four categories according to the Biopharmaceutics Classification System (BCS) proposed by Amidon et al. [49]. 

Biopharmaceutics Classification System Redefining BSC Solubility Class Boundary... 

Tab. 8.2. Biopharmaceutics Classification System (BCS). BCS is a permeability and solubility classification.

Fig. 15.5. The biopharmaceutics classification system (BCS). Drug-like molecules are grouped into four BCS classes based on their solubility and permeability. A drug is regarded as a highly soluble compound if the maximum dose given orally is soluble in 250 mL fluid in the...

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