title: Supersaturatable formulations for the enhanced oral absorption of sirolimus.
abstract: The purpose of this study was to develop supersaturatable formulations for the enhanced solubility and oral absorption of sirolimus. Supersaturatable formulations of hydrophilic polymers and/or surfactants were screened by formulation screening, which is based on solvent casting. The solid dispersion particles in the optimized formulations were prepared by spray drying. The particles were characterized in vitro and in vivo. The most effective supersaturatable formulation found in the formulation screening process was hydroxypropylmethyl cellulose (HPMC)-D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), followed by HPMC-Sucroester. In addition, the supersaturated state generated from HPMC-TPGS and HPMC-Sucroester 15 particles prepared by spray drying significantly improved the oral absorption of sirolimus in rats. Based on the pharmacokinetic parameters and supporting in vitro supersaturated dissolution data, the enhanced supersaturation properties of sirolimus led to enhanced in vivo oral absorption. In addition, the experimental results from the formulation screening used in our study could be useful for enhancing the bioavailability of sirolimus in preformulation and formulation studies.
authors: Department of Pharmaceutical Engineering, Inje University, Gimhae, Gyeongnam 621-749, Republic of Korea.
authors: Min-Soo
authors: MS
authors: Kim
authors: Jeong-Soo
authors: JS
authors: Kim
authors: Wonkyung
authors: W
authors: Cho
authors: Kwang-Ho
authors: KH
authors: Cha
authors: Hee-Jun
authors: HJ
authors: Park
authors: Junsung
authors: J
authors: Park
authors: Sung-Joo
authors: SJ
authors: Hwang
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry; D065347:Hypromellose Derivatives; D007166:Immunosuppressive Agents / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D013395:Sucrose / Q000031:analogs & derivatives / Q000737:chemistry; D014810:Vitamin E / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D005079:Excipients; D007166:Immunosuppressive Agents; C104509:gelucire 44-14; D014810:Vitamin E; D065347:Hypromellose Derivatives; C041567:sucrose monopalmitate; D011092:Polyethylene Glycols; D013395:Sucrose; D008747:Methylcellulose; C014225:tocophersolan; D020123:Sirolimus