title: Improved oral absorption of tacrolimus by a solid dispersion with hypromellose and sodium lauryl sulfate.
abstract: A novel surfactant-incorporated hydroxypropyl methylcellulose (HPMC) solid dispersion (SD) system was constructed in order to facilitate the release rate and oral absorption of tacrolimus (FK506), a poorly water-soluble immunosuppressant. Several emulsifiers including sodium lauryl sulfate (SLS), as drug release promotors, were employed with HPMC to fabricate SD using the solvent wetting method. The solid state characteristics using differential scanning calorimetry and X-ray powder diffraction, revealed that FK506 was molecularly distributed within all dispersions in amorphous form. The dissolution rates of FK506 in SLS-incorporated SDs were much higher than those in SDs prepared with HPMC alone, and even with stearoyl polyoxyl-32 glycerides or tocopheryl polyethylene glycol 1000 succinate. In particular, the greatest dissolution enhancement was obtained from the SD consisting of the drug, HPMC, and SLS in a weight ratio of 1:1:3, providing a 50-fold higher drug concentration within 15 min, compared with HPMC SD. In vivo absorption study in rats demonstrates that the optimized formula remarkably increased the oral absorption of FK506, providing about 4.0-fold greater bioavailability (p<0.05) compared with the marketed product (Prograf®, Astellas Pharma). These data suggest that a novel SLS/HPMC SD may be an advantageous dosage form of FK506, boosting the dissolution and absorption in gastrointestinal tract.
authors.affiliation: College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, South Korea.
authors.forename: Hyuck Jun
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, South Korea.
authors.forename: Hye In
authors.initials: HI
authors.lastname: Ahn
authors.affiliation: College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, South Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Park
authors.affiliation: College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, South Korea.
authors.forename: Myoung Jin
authors.initials: MJ
authors.lastname: Ho
authors.affiliation: College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, South Korea.
authors.forename: Dae Ro
authors.initials: DR
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, South Korea.
authors.forename: Ha Ra
authors.initials: HR
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, South Korea.
authors.forename: Jun Seo
authors.initials: JS
authors.lastname: Park
authors.affiliation: College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, South Korea.
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, South Korea. Electronic address: kangmj@dankook.ac.kr.
authors.forename: Myung Joo
authors.initials: MJ
authors.lastname: Kang
mesh_terms: D065966:Absorption, Physicochemical; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D065347:Hypromellose Derivatives / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D016559:Tacrolimus / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D007166:Immunosuppressive Agents; D013501:Surface-Active Agents; D014867:Water; D012967:Sodium Dodecyl Sulfate; D065347:Hypromellose Derivatives; D016559:Tacrolimus
keywords: Bioavailability; Dissolution; Hydroxypropyl methylcellulose; Sodium lauryl sulfate; Solid dispersion; Tacrolimus