Solubility, permeability, and their interplay

After oral administration, absorption of the drug from the dosage form depends on the release of the substance from the product, the dissolution/solubilization of the drug under physiological conditions, and the permeability throughout the gastrointestinal tract. Increasing the solubility or permeability of drugs represents a major challenge in the early stages of drug discovery. The biopharmaceutics classification system (BCS) offers guidelines for classification and may allow the identification of the steps necessary for improving the overall bioavailability of a given drug. In this chapter, we present the key factors dictating oral drug absorption; some of the approaches for solubility and permeability enhancement as well as the interplay between the two when using solubility-enabling drug formulations are introduced. The overview presented in this chapter highlights that the absorption of drugs, their effective delivery, and consequently their pharmacological effect are largely influenced by solubility and permeability. Moreover, it is essential to consider their interplay and to strike the optimal solubility-permeability balance in order to increase the overall drug absorption and bioavailability and maximize the chances of successful clinical development.