Oral bioavailability enhancement through supersaturation: an update and meta-analysis

Abstract

With the increasing number of poorly water-soluble compounds in drug discovery pipelines, supersaturating drug delivery systems (SDDS) have attracted increased attention as an effective bioavailability enhancing approach. However, a systematic and quantitative synopsis of the knowledge about performance of SDDS is currently lacking. Such analysis of the recent achievements is to provide insights for formulation scientists dealing with poorly soluble compounds. Areas covered: A systematic search of two evidence-based International databases, Medline and Embase, from 2010 to Dec 2015, has been performed. By conducting meta-analysis, box-plots, and correlation plots of the relevant data retrieved from literature, the current review addresses three quantitative questions: (1) how promising are SDDS for bioavailability enhancement? (2) which types of SDDS perform best? and (3) what are the most promising drug candidates? Four widely reported types of SDDS were compared: amorphous solid dispersions, nano-drug systems, supersaturable lipid-based formulations, and silica-based systems. Expert opinion: While SDDS formulations appear to be a promising candidate-enabling technique for drug development, the prediction of their in vivo performance by in vitro testing remains challenging. A transition from a trial-and-error development approach towards an approach guided by mechanistic insight, as well as the development of more efficient predictive tools for performance ranking is urgently needed.

Keywords: Supersaturation; bioavailability; formulation; oral; permeability; solubility.