BCS (Biopharmaceutic Classification System) is a classification approach in which drugs (APIs) are divided into four classes based on the extent (high or low) of their aqueous solubility and permeability through the GI tract wall, in particular intestinal. In this regard, these four classes are: (I) High Solubility and High Permeability drugs, (II) Low Solubility and High Permeability drugs, (III) High Solubility and Low Permeability drugs and, (IV) Low solubility and Low Permeability drugs. It is important to note that BCS relates only to drugs (APIs) and their characteristics, not the products.
These two factors (solubility and permeability) play a critical role in keeping all other factors equal for evaluating absorption characteristics of drugs in humans. For example, if four drugs, one from each class in equal doses, are administered in solution forms, all would show differences in absorption through GI tract or appearances in the bloodstream depending on their solubility/permeability characteristics. Potentially, the drug in group I would show fast and high absorption (least hindrance to absorption), the drug in group IV would show slow and erratic absorption (highest hindrance), while drugs in groups II and III would show absorption in between. Therefore, BCS certainly provides a good basis for assessing the potential absorption behavior of a drug in humans.
The use of BCS may not, however, be extended for product evaluation. There are at least four reasons for this: (1) as described above BCS relates to drugs only and not the products; (2) for products evaluation, one assesses the effect(s) of formulation and manufacturing attributes while keeping the drug and its strength constant. Thus solubility and permeability do not usually differ during product testing (3) BCS refers to aqueous solubility. However, the product may be evaluated in buffer solutions with or without solubilizers. (4) Often, reference is made about BCS in predicting the bioequivalence of two products, based on their in vitro release (dissolution) characteristics, e.g., in the case of developing IVIVC. It is important to note that, one does not use BCS criteria for evaluating bioequivalence (which is in fact assessment of in vivo drug dissolution/release). Similarly, therefore, in vitro assessment of equivalence of two products having the same drug and strength should not require the use of BCS classification as well.
In vitro drug release or dissolution, tests are conducted to assess the dissolution of the drug in a medium in which the drug must be freely soluble. The choice of medium is made prior to conducting a dissolution test so that the medium provides sufficient solubility to achieve the so-called sink condition. All drugs must be freely (highly) soluble in the dissolution medium. Therefore, for the evaluation of in vitro drug release, there are not two classes but one, i.e., the high solubility of the drug in the medium.
It appears that the use and application of BCS criteria for in vitro drug release testing requires a careful reconsideration, and its use can be reduced without any negative impact on products evaluation, however, with potential gains in economic efficiencies.