Abstract
Today classification of drug candidates on the Biopharmaceutics Classification System (BCS) has become an important issue in pharmaceutical researches. In this work, we provide a potential in silico approach to predict this system using two separately classification models of Dose number and Caco-2 cell permeability. 18 statistical linear and nonlinear models have been constructed based on 803 0-2D Dragon and 126 Volsurf+ molecular descriptors to classify the solubility and permeability properties. The voting consensus model of solubility (VoteS) showed a high accuracy of 88.7% in training and 92.3% in test set. Likewise, for the permeability model (VoteP), accuracy was 85.3% in training and 96.9% in test set. A combination of VoteS and VoteP appropriately predicts the BCS class of drugs (overall 73% with class I precision of 77.2%). This consensus system predicts the BCS allocations of 57 drugs appeared in the WHO Model List of Essential Medicines with 87.5% of accuracy. A simulation of a biopharmaceutical screening assay has been proved in a large data set of 37,377 compounds in different drug development phases (1, 2, 3 and launched), and NMEs. Distributions of BCS forecasts illustrate the current status in drug discovery and development. It is anticipated that developed QSPR models could offer the best estimation of BCS for NMEs in early stages of drug discovery.
Highlights
After almost 20 years of the introduction and exploration of the Biopharmaceutics Classification System (BCS), it has gained a major impact on the regulation and development of immediate release (IR) solid oral drug products [1,2]
200 oral drug products in the United States, Great Britain, Spain, and Japan were classified based on published solubility data and permeability data estimated by calculated log P [12]
It has been emphasized that the distribution of BCS class I, II, III, and IV in each classification are quite different
Summary
After almost 20 years of the introduction and exploration of the Biopharmaceutics Classification System (BCS), it has gained a major impact on the regulation and development of immediate release (IR) solid oral drug products [1,2]. According to BCS, IR solid oral dosage forms are categorized as having either rapid or slow in vitro dissolution, and classified based on aqueous solubility and intestinal permeability of the active pharmaceutical ingredient (API) [1]. This system has been formally adopted by the US FDA [3], the European agency EMEA [4] and the World Health Organization (WHO) [5] as a technical standard for waiving BE test requirements for oral drugs. Because it avoids unnecessary drug exposures to healthy subjects, while maintaining the high public health standard for therapeutic equivalence, the BCS is, without doubt, a potential tool for speeding up and reducing the cost of drug development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
