ABSTRACT
The biopharmaceutics classification system (BCS) is a drug development tool that allows estimation of the relative contributions of the three major factors that govern the rate and extent of oral absorption of a drug from solid oral dosage forms, namely dissolution, solubility and permeability. The permeability of drugs can be ascertained by in vitro methods with epithelial cell cultures. However, there are a number of cell lines used for evaluating intestinal absorption, and the protocols for conducting the permeability experiments differ among laboratories. Therefore, regulatory acceptance of in vitro permeability data in the context of the BCS is based on method suitability where the goal is to classify a drug as having high permeability (HP) or low permeability (LP). A cell culture method is considered to be suitable when it has established a rank-order relationship between experimental permeability values of model drugs and the extent of intestinal absorption in humans. After demonstrating method suitability and maintaining the same protocol, the method can be used to classify a drug’s permeability when used in conjunction with standard compounds. The method must also take into consideration a drug’s stability and solubility, whether the drug is passively or actively absorbed, and if the cell line expresses efflux pumps. The BCS relies on method suitability and internal standards for in vitro permeability assays, as opposed to a standardized protocol, thus allowing for variability in cell lines and methods among laboratories while encouraging advancements in the existing technology.
