Biopharmaceutical Classification System defined

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. 

The Biopharmaceutics Classification System (BCS)3 defines four classes of compounds based upon solubility and permeability. Particle size and size distribution... 

Aqueous solubility of ionizable molecules at different pH values is an important characteristic because it indicates the potential substance behavior in the stomach and intestinal tract and its potential impact on bioavailability. Moreover, it also provides important information for formulation scientists to define the class of a drug substance in the Biopharmaceutics Classification System (BCS), a regulatory guidance for bioequivalence studies. The BCS is a scientific framework proposed by the FDA to classify drug substances based on their aqueous solubility and intestinal permeability and defines important parameters in the selection of drug candidates into development. According to the BCS, drug substances are classified as shown in Table 12-4. 

Figure 3.1 The Biopharmaceutics Classification System as defined by Amidon et al. [6]. The BCS is a classification of drug substances according to their solubility and permeability properties, in orderto stand forthe most fundamental viewofthe drug intestinal absorption process following oral administration.

Figure 1. Biopharmaceutical Classification System and Development Classification System. Class I compounds are defined as soluble and permeable through the gastrointestinal tract, Class II as poorly soluble but permeable through the GI tract, Class III as soluble but poorly permeable and Class IV as both poorly soluble and permeable. The further classification of Class II and III (simple and complex) is intended to provide additional data on the develop-ability of the drug candidate.

Solid dispersion is defined as one type of method to produce an amorphous compound by incorporating a hydrophobic drug into a hydrophilic carrier (Chiou and Riegelman 1971). It is one of the most studied methods to solubilize and to enhance dissolution rate of biopharmaceutical classification system (BCS) class 2 compounds. For instance, a solid dispersion of ritonavir (Law et al. 2001), ER-3421 (a dual 5-lipoxygenase/cyclooxygenase inhibitor Kushida et al. 2002), was found to have a much higher dissolution rate than the crystalline counterpart and resulted in higher area under curve (AUC) and Cmax in the in vivo study. 

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

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