title: Effect of magnesium carbonate on the solubility, dissolution and oral bioavailability of fenofibric acid powder as an alkalising solubilizer.
abstract: 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 Cmax values compared to choline fenofibrate in rats. However, the mixture resulted in plasma concentrations, AUC and Cmax 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.
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea.|Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-myeon, 893-5, Hwaseong, 445-913, Gyeonggi-Do, South Korea.
authors.forename: Kyeong Soo
authors.initials: KS
authors.lastname: Kim
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea.
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea.
authors.forename: Sung Giu
authors.initials: SG
authors.lastname: Jin
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea.
authors.forename: Dong Wuk
authors.initials: DW
authors.lastname: Kim
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea.
authors.forename: Dong Shik
authors.initials: DS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan, 712-749, South Korea.
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan, 712-749, South Korea.
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.affiliation: College of Pharmacy, Inje University, Inje-ro 197, Gimhae, 621-749, South Korea.
authors.forename: Kwan Hyung
authors.initials: KH
authors.lastname: Cho
authors.affiliation: National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, 56 Yangming Road, Nanchang, 330006, Jiangxi, China.
authors.forename: Dong Xun
authors.initials: DX
authors.lastname: Li
authors.affiliation: Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-myeon, 893-5, Hwaseong, 445-913, Gyeonggi-Do, South Korea. jswoo@hanmi.co.kr.
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Woo
authors.affiliation: College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea. hangon@hanyang.ac.kr.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005079:Excipients / Q000737:chemistry*; D011345:Fenofibrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D008274:Magnesium / Q000737:chemistry*; D008297:Male; D010316:Particle Size; D011208:Powders; D017207:Rats, Sprague-Dawley; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D005079:Excipients; D000960:Hypolipidemic Agents; D011208:Powders; C005479:magnesium carbonate; C006012:fenofibric acid; D008274:Magnesium; D011345:Fenofibrate
keywords: Bioavailability; Dissolution; Fenofibric acid; Magnesium carbonate; Solubility