Quantitative Structure-Property Relationship Analysis of Drugs’ Pharmacokinetics Within the Framework of Biopharmaceutics Classification System Using Simplex Representation of Molecular Structure

The Biopharmaceutics Classification System (BCS) categorizes drugs into one of four biopharmaceutical classes according to their water solubility and membrane permeability characteristics and broadly allows the prediction of the rate-limiting step in the intestinal absorption process following oral administration. When combined with the in vitrodissolution characteristics of the drug product, the BCS takes into account three major factors: solubility, intestinal permeability, and dissolution rate, all of which govern the rate and extent of oral drug absorption from immediate-release (IR) solid oral-dosage forms. The concept of BCS provides a better understanding of the relationship between drug release from the product and the absorption process. This report reviews the current status of computational tools in predicting the base properties (aqueous solubility, and passive absorption) of the BCS and explores the application of the Simplex representation of molecular structure (SiRMS) QSAR approach in absorption (bioavailability) research. The main advantages of SiRMS are consideration of the different physico–chemical properties of atoms, high robustness, predictivity, and interpretability of developed models that creates good opportunities for molecular design. The reliability of developed QSAR models as predictive virtual screening tools and their utility for targeted drug design were validated by subsequent synthetic and biological experiments. The SiRMS approach was implemented as “HiT QSAR” software. In addition, we provide our perspective on the progress of research into an in silico equivalent to the BCS.