Do Phospholipids Boost or Attenuate Drug Absorption? In Vitro and In Vivo Evaluation of Mono- and Diacyl Phospholipid-Based Solid Dispersions of Celecoxib

Phospholipids are amphiphilic lipids with versatile properties making them promising excipients for enabling formulations for oral drug delivery. Unfortunately, systematic studies on how phospholipid type and content affect oral absorption are rare. Often, only one phospholipid type is used for the formulation development and only one formulation, optimized according to in vitro parameters, is included in oral bioavailability studies. Using this approach, it is unclear if a certain in vitro parameter is predictive for the in vivo performance. In this study, a labor-saving in vitro permeation screening method was combined with a pharmacokinetic study in rats to for the first time systematically compare two types of phospholipid-based solid dispersions. The dispersions contained the drug celecoxib and monoacyl or diacyl phosphatidylcholine at different drug-to-phospholipid ratios. The in vitro screening revealed: 1) none of the formulations with high phospholipid content increased permeation, 2) phospholipid content was negatively correlated with permeation, and 3) mono and diacyl-phosphatidylcholine formulations performed equally. The pharmacokinetic study revealed: 1) At low phospholipid content absorption was enhanced, 2) phospholipid content was negatively correlated with absorption, and 3) monoacyl and diacyl phosphatidylcholine formulations performed equally. Apart from the reference (suspension), the in vitro permeation screening thus predicted the formulations in vivo performance. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

Automated summary

Phospholipids play a crucial role in oral absorption, with systematic studies rare in this area. This study systematically compared two types of phospholipid-based solid dispersions, revealing a negative correlation between phospholipid content and oral absorption. The in vitro permeation screening was able to predict the in vivo performance of the formulations, showcasing its potential as a predictive tool.