Improvement of the dissolution rate and bioavailability of fenofibrate by the supercritical anti-solvent process.

Int J Pharm

Department of Physical Pharmacy, College of Pharmacy, Chungnam National University, Republic of Korea; Institute of Drug Research and Development, Chungnam National University, Republic of Korea. Electronic address:

Published: June 2019

The purpose of this study was to improve solubility and oral bioavailability of fenofibrate via solid dispersion (SD) using a supercritical anti-solvent (SAS) process with amphipathic polymers P407 and TPGS. Solid dispersion techniques have been widely used to enhance the solubility and dissolution profiles of poorly soluble drugs. Fenofibrate is classified as a Biopharmaceutics Classification System class II compound because of its low solubility and high gastrointestinal permeability. Two copolymers were selected based on solubility and dissolution tests. Their physicochemical properties were compared with those prepared by conventional solvent evaporation (CSE). The SD formulations containing fenofibrate were successfully prepared using the SAS and CSE methods. The dissolution rate (%) of fenofibrate at 60 min was significantly improved compared with the solution of raw fenofibrate (19.5% ± 3.7%) by 95.1% ± 2.5% and 93.7% ± 4.1% using the SAS and the CSE process, respectively. This approximately four-fold increase in dissolution rate indicates that oral bioavailability can be enhanced. In addition, pharmacokinetic study was analyzed using the area under the curve (AUC) and C values of SAS-SD and CSE-SD in rats. The AUC was 2.1 times higher and C was 1.9 times higher in SAS-SD, indicating higher concentrations of fenofibrate in the blood. In a pharmacodynamic study to evaluate the efficacy of the drug in hyperlipidemic rat models, SAS-SD showed strong lipid-lowering effects including cholesterol (1.9-fold) and triglycerides (3.3-fold), than CSE-SD. Taken together, these results suggested that SAS-SD has excellent potential as a formulation for the poorly soluble drug fenofibrate.

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http://dx.doi.org/10.1016/j.ijpharm.2019.04.051DOI Listing

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