Aminoalkyl methacrylate copolymers for improving the solubility of tacrolimus. I: Evaluation of solid dispersion formulations.

Takatsune Yoshida, Ippei Kurimoto, Keiichi Yoshihara, Hiroyuki Umejima, Naoki Ito, Shunsuke Watanabe, Kazuhiro Sako, Akihiko Kikuchi

Index: Int. J. Pharm. 428(1-2) , 18-24, (2012)

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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.Copyright © 2012 Elsevier B.V. All rights reserved.