TY - JOUR
T1 - Do Phospholipids Boost or Attenuate Drug Absorption? In Vitro and In Vivo Evaluation of Mono- and Diacyl Phospholipid-Based Solid Dispersions of Celecoxib
AU - Jacobsen, Ann Christin
AU - Ejskjær, Lotte
AU - Brandl, Martin
AU - Holm, René
AU - Bauer-Brandl, Annette
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - Amorphous solid dispersion
KW - In vitro model
KW - In vitro/in vivo correlation (IVIVC)
KW - Intestinal absorption
KW - Lipid-based formulation
KW - Permeability
KW - Pharmacokinetics
KW - Phospholipid
KW - Poorly water-soluble drug
KW - Supersaturation
KW - Amorphous solid dispersion
KW - In vitro model
KW - In vitro/in vivo correlation (IVIVC)
KW - Intestinal absorption
KW - Lipid-based formulation
KW - Permeability
KW - Pharmacokinetics
KW - Phospholipid
KW - Poorly water-soluble drug
KW - Supersaturation
U2 - 10.1016/j.xphs.2020.08.009
DO - 10.1016/j.xphs.2020.08.009
M3 - Journal article
C2 - 32827494
AN - SCOPUS:85090482779
SN - 0022-3549
VL - 110
SP - 198
EP - 207
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 1
ER -