title: Novel fenofibric acid-loaded controlled release pellet bioequivalent to choline fenofibrate-loaded commercial product in beagle dogs.
abstract: The objective of this study was to develop a novel fenofibric acid-loaded controlled release pellet showing enhanced, or equivalent to, bioavailability compared with two commercially available products containing fenofibrate or choline fenofibrate. The effect of solubilizing agents on drug solubility and the impact of fillers on core properties were investigated. Among them, magnesium carbonate most improved drug solubility, and κ-carrageenan provided the best spherical cores. The fenofibric acid-loaded pellet was prepared with magnesium carbonate and κ-carrageenan employing the extrusion/spheronizing technique followed by coating with ethylcellulose. Furthermore, dissolution and pharmacokinetic study in beagle dogs were performed compared to the fenofibrate-loaded commercial tablet (FCT) and choline fenofibrate-loaded commercial mini-tablet (CFCM). This fenofibric acid-loaded pellet showed controlled release of the drug in phosphate buffer (pH 6.8) and 0.025 M sodium laurylsulfate within 4h. Furthermore, this pellet and CFCM exhibited similar dissolution profiles. Plasma concentrations greater than 1,000 ng/ml were maintained from 30 min to 8h, suggesting a sustained release pattern. Also, the fenofibric acid-loaded pellet gave significantly higher AUC and Cmax values than FCT, indicating that it improved the bioavailability of fenofibrate due to enhanced solubility and sustained release. In addition, this pellet and CFCM were not significantly different in terms of pharmacokinetic parameters including AUC, Cmax and Tmax. Thus, this pellet was bioequivalent to CFCM in beagle dogs. In conclusion, this fenofibric acid-loaded controlled release pellet would be a potential alternative to the choline fenofibrate-loaded commercial product.
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, Gyeonggi-Do 445-913, South Korea.
authors.forename: Kyung 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: 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: Omer
authors.initials: O
authors.lastname: Mustapha
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: Abid Mehmood
authors.initials: AM
authors.lastname: Yousaf
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; Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-myeon, 893-5 Hwaseong, Gyeonggi-Do 445-913, South Korea.
authors.forename: Young Hun
authors.initials: YH
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: Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-myeon, 893-5 Hwaseong, Gyeonggi-Do 445-913, South Korea. Electronic address: 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. Electronic address: hangon@hanyang.ac.kr.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002351:Carrageenan / Q000737:chemistry; D002794:Choline / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000493:pharmacokinetics; D004285:Dogs; D011345:Fenofibrate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013607:Tablets / Q000737:chemistry* / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D002351:Carrageenan; C006012:fenofibric acid; D002794:Choline; D011345:Fenofibrate
keywords: Bioavailability; Bioequivalence; Controlled release pellet; Dissolution; Fenofibric acid