title: Aminoalkyl methacrylate copolymers for improving the solubility of tacrolimus. I: Evaluation of solid dispersion formulations.
abstract: The aim of this study was to investigate the effect of Eudragit E/HCl (E-SD) on the reprecipitation of a poorly water-soluble drug, tacrolimus. To evaluate the inhibition of reprecipitation of E-SD, reprecipitation studies on tacrolimus were conducted using a dissolution test method. Solubility of tacrolimus was measured at regular intervals in a dissolution media, in which tacrolimus was dissolved in ethanol, and the test media contained additives for inhibiting precipitation. Supersaturation profiles of tacrolimus were observed, and were maintained for 24h only with E-SD. Solid dispersion formulations of tacrolimus prepared with hydroxypropylmethylcellulose (HPMC) or E-SD in different drug/carrier ratios were also investigated. Solid dispersions prepared with E-SD showed higher solubility of tacrolimus compared with that of HPMC. In the E-SD formulation, the drug solubility influences to drug/carrier ratio. The formulation of drug/E-SD (1/5) showed the highest drug solubility. Thus, it may be inferred that a definite drug/carrier ratio exists to increase drug solubility. Further, by mixing E-SD the solid dispersion prepared with HPMC showed enhanced drug solubility.
authors.affiliation: Pharmaceutical Research and Technology Labs, Astellas Pharma Inc., 180 Ozumi, Yaizu, Shizuoka 425-0072, Japan. takatsune.yoshida@astellas.com
authors.forename: Takatsune
authors.initials: T
authors.lastname: Yoshida
authors.forename: Ippei
authors.initials: I
authors.lastname: Kurimoto
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yoshihara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Umejima
authors.forename: Naoki
authors.initials: N
authors.lastname: Ito
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Watanabe
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sako
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kikuchi
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008768:Methylmethacrylates / Q000737:chemistry*; D012995:Solubility; D016559:Tacrolimus / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008768:Methylmethacrylates; D014867:Water; C102808:Eudragit-E; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D016559:Tacrolimus