The Biopharmaceutics Drug Classification Systems

A biopharmaceutics drug classification scheme (BDCS) for correlating in vitro drug product dissolution and in vivo bioavailabUity is based on recognizing that drug dissolution and GI permeability are the fundamental parameters controlling the rate and extent of drug absorption. The BDCS is defined as  

Case 1. High solubility-high-permeability drugs. 

Case 3. High solubility-low-permeability drugs, and Case 4. Low solubility-low-permeability drugs. 

The BDCS should serve the needs of the earliest stages of discovery research where it can be useful in predicting routes of elimination, effects of efflux, and absorptive transporters on oral absorption, when transporter-enzyme interplay will yield clinically significant effects, such as low bioavailability and drug-drug interactions, the direction and importance of food effects, and transporter effects on postabsorption systemic levels following oral and intravenous doses. 

Several generalizations can be made about the interplay of transporters and the BDCS classification. 

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Table 1 The Biopharmaceutics Drug Classification System as Defined by the Food and Drug Administration and Modified by Recent Findings... 

Amidon, G. L., Lennernas, H., Shah, V. P., et al. A theoretical basis for a biopharmaceutics drug classification system the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm. Res. 12 413 20,1995. 

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. 

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]. 

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...

Moller H (2002) The biopharmaceutical classification system (BCS) and its usage. Drugs Made in Germany 45 63-65. 

Volpe DA, Moller H, Yu LX (2002) Regulatory acceptance of in vitro permeability studies in the context of the biopharmaceutics classification system. In Lehr CM (ed.) Cell Culture Models of Biological Barriers In Vitro Test Systems for Drug Absorption and Delivery. Taylor Francis Publishing Group, London New York, pp. 130-139. 

Since solubility and permeability are the two most important factors influencing oral absorption of drugs, the following biopharmaceutical classification system (BCS) for drug substances, based on the work by Amidon et al.,67 has been recommended by the FDA 68... 

Yazdanian, M., Briggs, K., Jankovsky, C., and Hawi, A., The "high solubility" definition of the current FDA guidance on biopharmaceutics classification system may be too strict for acidic drugs, Pharm. Res., 21, 293, 2004. 

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