Prediction of Solubility and Permeability Class Membership: Provisional BCS Classification of the World’s Top Oral Drugs

Abstract

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. Since its introduction in 1995, the BCS has generated remarkable impact on the global pharmaceutical sciences arena, in drug discovery, development, and regulation, and extensive validation/discussion/extension of the BCS is continuously published in the literature. The BCS has been effectively implanted by drug regulatory agencies around the world in setting bioavailability/bioequivalence standards for immediate-release (IR) oral drug product approval. In this review, we describe the BCS scientific framework and impact on regulatory practice of oral drug products and review the provisional BCS classification of the top drugs on the global market. The Biopharmaceutical Drug Disposition Classification System and its association with the BCS are discussed as well. One notable finding of the provisional BCS classification is that the clinical performance of the majority of approved IR oral drug products essential for human health can be assured with an in vitro dissolution test, rather than empirical in vivo human studies.

Interplay of Dissolution, Solubility, and Nonsink Permeation Determines the Oral Absorption of the Hedgehog Pathway Inhibitor GDC-0449 in Dogs: An Investigation Using Preclinical Studies and Physiologically Based Pharmacokinetic Modeling

“…Biopharmaceutical Classification System (BCS), GDC-0449 is considered a BCS class II compound (Dahan et al, 2009) based on its very low solubility and high Caco-2 permeability. The oral absorption of BCS class II compounds is usually limited by particle size effects or intestinal fluid solubility on the dissolution process.…”

In Vitro Release Studies of Carbamazepine Tablets and Benzoyl Metronidazole Suspensions Using the Flow-Through Cell Apparatus and Simulated Gastrointestinal Fluids

“…According to the Biopharmaceutics Classification System, carbamazepine is a Class II drug owing to its low solubility/high permeability; metronidazole is a Class I drug owing to its high solubility/high permeability [4]. However, Kasim et al [5] have classified metronidazole as a Class III drug (high solubility/low permeability), and a private company specializing in drug delivery studies [6,7] has classified it as a Class IV drug (low solubility/low permeability). Both compounds are manufactured as generic tablets and suspensions, and to determine whether these drugs are safely interchangeable, evaluation of their in vitro release under conditions that simulate the natural environment of the gastrointestinal tract is very important.…”

Evaluation of the Membrane Permeability (PAMPA and Skin) of Benzimidazoles with Potential Cannabinoid Activity and their Relation with the Biopharmaceutics Classification System (BCS)

“…Some authors sustain that an ideal Log P oct value is within 1 and 4 because in this range, the molecule has enough lipid affinity to cross membranes and enough water affinity to diffuse and dissolve in body fluids (6,(8)(9)(10). The value of Log P oct is only an estimate of the permeability since the said parameter does not consider absorption through transporters, which is an important absorption mechanism of drugs (3).…”