Effect of magnesium carbonate on the solubility, dissolution and oral bioavailability of fenofibric acid powder as an alkalising solubilizer

• Published in: Archives of pharmacal research 2016, 39(4), , pp.531-538
• Main Authors: Kim, Kyeong Soo, Kim, Jeong Hyun, Jin, Sung Giu, Kim, Dong Wuk, Kim, Dong Shik, Kim, Jong Oh, Yong, Chul Soon, Cho, Kwan Hyung, Li, Dong Xun, Woo, Jong Soo, Choi, Han-Gon
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Biological Availability; Chromatography, High Pressure Liquid; Excipients - chemistry; Fenofibrate - administration & dosage; Fenofibrate - analogs & derivatives; Fenofibrate - blood; Fenofibrate - chemistry; Fenofibrate - pharmacokinetics; Hypolipidemic Agents - administration & dosage; Hypolipidemic Agents - blood; Hypolipidemic Agents - chemistry; Hypolipidemic Agents - pharmacokinetics; Magnesium - chemistry; Male; Medicine; Particle Size; Pharmacology/Toxicology; Pharmacy; Powders; Rats, Sprague-Dawley; Research Article; Solubility; Spectroscopy, Fourier Transform Infrared; Surface Properties; Technology, Pharmaceutical - methods; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-015-0701-9

To investigate the possibility of developing a novel oral pharmaceutical product using fenofibric acid instead of choline fenofibrate, the powder properties, solubility, dissolution and pharmacokinetics in rats of fenofibrate, choline fenofibrate and fenofibric acid were compared. Furthermore, the effect of magnesium carbonate, an alkalising agent on the solubility, dissolution and oral bioavailability of fenofibric acid was assessed, a mixture of fenofibric acid and magnesium carbonate being prepared by simple blending at a weight ratio of 2/1. The three fenofibrate derivatives showed different particle sizes and melting points with similar crystalline shape. Fenofibric acid had a significantly higher aqueous solubility and dissolution than fenofibrate, but significantly lower solubility and dissolution than choline fenofibrate. However, the fenofibric acid/magnesium carbonate mixture greatly improved the solubility and dissolution of fenofibric acid with an enhancement to levels similar with those for choline fenofibrate. Fenofibric acid gave lower plasma concentrations, AUC and C max values compared to choline fenofibrate in rats. However, the mixture resulted in plasma concentrations, AUC and C max values levels not significantly different from those for choline fenofibrate. Specifically, magnesium carbonate increased the aqueous solubility, dissolution and bioavailability of fenofibric acid by about 7.5-, 4- and 1.6-fold, respectively. Thus, the mixture of fenofibric acid and magnesium carbonate at the weight ratio of 2/1 might be a candidate for an oral pharmaceutical product with improved oral bioavailability.