title: Development of novel fast-dissolving tacrolimus solid dispersion-loaded prolonged release tablet.
abstract: The goal of this research was to develop a novel prolonged release tablet bioequivalent to the commercial sustained release capsule. A number of tacrolimus-loaded fast-dissolving solid dispersions containing various amounts of DOSS were prepared using the spray drying technique. Their solubility, dissolution and pharmacokinetics in rats were studied. DOSS increased drug solubility and dissolution in the solid dispersions. Compared with the drug powder, the solubility, dissolution and bioavailability of tacrolimus with the fast-dissolving solid dispersion containing tacrolimus/HP-β-CD/DOSS in the weight ratio of 5:40:4 were boosted by approximately 700-, 30- and 2-fold, respectively. Several tablet formulations were accomplished with this solid dispersion in combination with various ratios of HPMC/ethylcellulose. The release behaviour and pharmacokinetic studies in beagle dogs were assessed compared with the commercial prolonged release capsule. A decrease in HPMC/ethylcellulose ratios reduced the dissolution of tacrolimus from the tablets. Particularly, the tacrolimus-loaded prolonged release tablet consisting of fast-dissolving tacrolimus solid dispersion, HPMC, ethylcellulose and talc at the weight ratio of 20:66:112:2 exhibited a dissolution profile similar to that produced by the commercial prolonged release capsule. Furthermore, there were no significant differences in the AUC, Cmax, Tmax and MRT values between them in beagle dogs. Consequently, this tacrolimus-loaded prolonged release tablet might be bioequivalent to the tacrolimus-loaded commercial capsule.
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea; Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-myeon, 893-5, Hwaseong, Gyeonggi-Do 445-913, South Korea.
authors.forename: Yong-Il
authors.initials: YI
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-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: Abid Mehmood
authors.initials: AM
authors.lastname: Yousaf
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: 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, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea. Electronic address: csyong@yumail.ac.kr.
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea; 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: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004143:Dioctyl Sulfosuccinic Acid / Q000737:chemistry; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry; D015195:Drug Design; D007166:Immunosuppressive Agents / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D012995:Solubility; D013607:Tablets; D016559:Tacrolimus / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D013627:Talc / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007166:Immunosuppressive Agents; D013607:Tablets; D047392:beta-Cyclodextrins; D004143:Dioctyl Sulfosuccinic Acid; D013627:Talc; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D016559:Tacrolimus
keywords: Bioequivalence in beagle dogs; Ethylcellulose; Fast-dissolving solid dispersion; Hydroxypropyl methylcellulose; Prolonged release tablet; Tacrolimus