Application of data mining approach to identify drug subclasses based on solubility and permeability

Abstract

Solubility and permeability are recognized as key parameters governing drug intestinal absorption and represent the basis for biopharmaceutics drug classification. The Biopharmaceutics Classification System (BCS) is widely accepted and adopted by regulatory agencies. However, currently established low/high permeability and solubility boundaries are the subject of the ongoing scientific discussion. The aim of the present study was to apply data mining analysis on the selected drugs data set in order to develop a human permeability predictive model based on selected molecular descriptors, and to perform data clustering and classification to identify drug subclasses with respect to dose/solubility ratio (D/S) and effective permeability (Peff). The Peff values predicted for 30 model drugs for which experimental human permeability data are not available were in good agreement with the reported fraction of drug absorbed. The results of clustering and classification analysis indicate the predominant influence of Peff over D/S. Two Peff cut‐off values (1 × 10−4 and 2.7 × 10−4 cm/s) have been identified indicating the existence of an intermediate group of drugs with moderate permeability. Advanced computational analysis employed in the present study enabled the recognition of complex relationships and patterns within physicochemical and biopharmaceutical properties associated with drug bioperformance.

Comparative evaluation study of polycomplex carriers based on Eudragit® EPO/S100 copolymers prepared in different media

“…DS and TEO were also chosen since these APIs belong to the different classes of the biopharmaceutical classification system (BCS) 34 . TEO has high solubility and high permeability (I class of BCS), 35 whereas DS has low solubility and high permeability (II class of BCS) 36 …”

Integrated biopharmaceutical approach in pharmaceutical development and drug characterization: General concept and application

“…More recently, it also received considerable criticism for being overly conservative with respect to the established pH-solubility criteria, available media volume, applicability for the specific patient groups (such as paediatric population), veterinary applications, and applicability for other routes of drug administration (i.e. inhalation route, topical application), so that several modified classification systems have been proposed to address these limitations [22][23][24][25][26][27][28][29][30][31].…”

In Vitro Dissolution and in Silico Modeling Shortcuts in Bioequivalence Testing

“…To classify drugs based on their aqueous solubility and intestinal permeability, the Biopharmaceutics Classification System (BCS) represents a cornerstone for four-category classification. The BCS categories are: class I (high solubility, high permeability), class II (low solubility, high permeability), class III (high solubility, low permeability), and class IV (low solubility, low permeability) [1]. BCS is of particular significance because it is required in any new drug application (NDA) and allows for biowaivers of classes I and III drugs when applying for abbreviated new drug application (ANDA) [2].…”