Current and evolving approaches for improving the oral permeability of BCS Class III or analogous molecules

• Published in: Drug development and industrial pharmacy Vol. 43; no. 2; p. 177
• Main Authors: Dave, Vivek S, Gupta, Deepak, Yu, Monica, Nguyen, Phuong, Varghese Gupta, Sheeba
• Format: Journal Article
• Language: English
• Published: England 01.02.2017
• Subjects: Biological Availability; Biopharmaceutics - classification; Biopharmaceutics - standards; Drug Discovery; Hydrophobic and Hydrophilic Interactions; Permeability; Solubility; United States; United States Food and Drug Administration; BCS Class III; nanotechnology; Permeability; counterion; ion-pairing; prodrugs; liposome; permeation enhancer
• ISSN: 1520-5762
• DOI: 10.1080/03639045.2016.1269122

The Biopharmaceutics Classification System (BCS) classifies pharmaceutical compounds based on their aqueous solubility and intestinal permeability. The BCS Class III compounds are hydrophilic molecules (high aqueous solubility) with low permeability across the biological membranes. While these compounds are pharmacologically effective, poor absorption due to low permeability becomes the rate-limiting step in achieving adequate bioavailability. Several approaches have been explored and utilized for improving the permeability profiles of these compounds. The approaches include traditional methods such as prodrugs, permeation enhancers, ion-pairing, etc., as well as relatively modern approaches such as nanoencapsulation and nanosizing. The most recent approaches include a combination/hybridization of one or more traditional approaches to improve drug permeability. While some of these approaches have been extremely successful, i.e. drug products utilizing the approach have progressed through the USFDA approval for marketing; others require further investigation to be applicable. This article discusses the commonly studied approaches for improving the permeability of BCS Class III compounds.