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

ABSTRACT

Introduction: 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
• solubility
• permeability
• bioavailability
• formulation
• oral

Article highlights

• The use of supersaturating drug delivery systems (SDDS) for oral bioavailability enhancement of poorly soluble compounds has been gaining momentum over the past decade.

• However, a systematic, critical and quantitative summary of the achievements in recent work on SDDS is lacking.

• From our systematic search, a total of 266 relevant articles with respect to supersaturation and bioavailability/permeability-enhancement of SDDS were identified and a final of 61 eligible articles were meta-analyzed.

• With the overall ability for drugs to enhance their solubility (26.7 fold), permeability (3.1 fold), and oral bioavailability (5.6 fold), SDDS formulations appear to be a promising candidate-enabling technique for successful drug development.

• A comparison among the SDDS formulation types indicates that nano-drug systems represent the most propitious approach to enhance supersaturation and oral bioavailability, closely followed by the amorphous solid dispersions.

• Development of effective predictive tools for performance ranking of SDDS formulations is urgently needed.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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Funding

This paper was not funded.