Phospholipid-based solid drug formulations for oral bioavailability enhancement: A meta-analysis

Abstract

Low bioavailability nowadays often represents a challenge in oral dosage form development. Solid formulations composed of drug and phospholipid (PL), which, upon contact with water, eventually form multilamellar liposomes (i.e. 'proliposomes'), are an emerging approach to solve such issue. Regarded as an 'improved' version of liposomes concerning storage stability, the potential and versatility of a range of such formulations for oral drug delivery have been extensively discussed. However, a systematic and quantitative analysis of the studies that applied solid PL for oral bioavailability enhancement is currently lacking. Such analysis is necessary for providing an overview of the research progress and addressing the question on how promising this approach can be on bioavailability enhancement. The current review performed a systematic search of references in three evidence-based English databases, Medline, Embase, and SciFinder, from the year of 1985 up till March 2015. A total of 112 research articles and 82 patents that involved solid PL-based formulations were identified. The majority of such formulations was intended for oral drug delivery (55%) and was developed to address low bioavailability issues (49%). A final of 54 studies that applied such formulations for bioavailability enhancement of 43 different drugs with poor water solubility and/or permeability were identified. These proof-of-concept studies with in vitro (n=31) and/or animal (n=23) evidences have been systematically summarized. Meta-analyses were conducted to measure the overall enhancement power (percent increase compared to control group) of solid PL formulations on drugs' solubility, permeability and oral bioavailability, which were found to be 127.4% (95% CI [86.1, 168.7]), 59.6% (95% CI [30.1, 89.0]), and 18.5% (95% CI [10.1, 26.9]) respectively. Correlations between the enhancement factors and in silico physiochemical properties of drugs were also performed to check if such approach can be used to identify the best candidates for oral solid PL formulation. In addition to scientific literature, 13 solid PL formulation-related patents that addressed the issue of low oral bioavailability have been identified and summarized; whereas no clinical study was identified from the current search. By providing systematic information and meta-analysis on studies that applied the principle of 'proliposomes' for oral bioavailability enhancement, the current review should be insightful for formulation scientists who wish to adopt the PL based approach to overcome the solubility, permeability and bioavailability issues of orally delivered drugs.

Keywords: Bioavailability; Oral; Phospholipid; Proliposome; Solid dispersion; Solubility.