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Dive into the research topics where Hiroyuki Umejima is active.

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Featured researches published by Hiroyuki Umejima.


International Journal of Pharmaceutics | 2012

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

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.


Colloid and Polymer Science | 2013

Effects of dissolved state of aminoalkyl methacrylate copolymer E/HCl on solubility enhancement effect for poorly water-soluble drugs

Takatsune Yoshida; Ippei Kurimoto; Hiroyuki Umejima; Shunsuke Watanabe; Kazuhiro Sako; Akihiko Kikuchi

Eudragit® E/HCl salt (E–SD) displays a good antireprecipitation effect on solid dispersion formulations of poorly water-soluble drugs. To elucidate the mechanism underlying the antireprecipitation effect of E–SD, a study on supersaturation was conducted using a dissolution test method with test fluids at varying pH and ionic strength values. Both pH and ionic strength of the test fluid were shown to influence the antireprecipitation effect of E–SD; a strong antireprecipitation effect was observed at a neutral pH (pH 6∼7) and an ionic strength of 0.1 to 1.0. To investigate E–SD in its dissolved state in each test fluid, fluorescence measurement using pyrene as a probe molecule and dynamic light-scattering (DLS) measurement were conducted. The total fluorescence intensity of pyrene increased with increasing E–SD concentrations. Further, small nanoparticles were observed using DLS measurement. These results suggest that E–SD may form a micelle-like structure in the dissolved test fluid.


International Journal of Pharmaceutics | 2015

Release mechanisms of tacrolimus-loaded PLGA and PLA microspheres and immunosuppressive effects of the microspheres in a rat heart transplantation model.

Ryo Kojima; Takatsune Yoshida; Hiroaki Tasaki; Hiroyuki Umejima; Masashi Maeda; Yasuyuki Higashi; Shunsuke Watanabe; Naoto Oku

The objective of this study was to elucidate the release and absorption mechanisms of tacrolimus loaded into microspheres composed of poly(lactic-co-glycolic acid) (PLGA) and/or polylactic acid (PLA). Tacrolimus-loaded microspheres were prepared by the o/w emulsion solvent evaporation method. The entrapment efficiency correlated with the molecular weight of PLGA, and the glass transition temperature of PLGA microspheres was not decreased by the addition of tacrolimus. These results indicate that intermolecular interaction between tacrolimus and the polymer would affect the entrapment of tacrolimus in the microspheres. Tacrolimus was released with weight loss of the microspheres, and the dominant release mechanism of tacrolimus was considered to be erosion of the polymer rather than diffusion of the drug. The whole-blood concentration of tacrolimus in rats was maintained for at least 2 weeks after a single subcutaneous administration of the microspheres. The pharmacokinetic profile of tacrolimus following subcutaneous administration was similar to that following intramuscular administration, suggesting that the release and dissolution of tacrolimus, rather than the absorption of the dissolved tacrolimus, were rate-limiting steps. Graft-survival time in a heart transplantation rat model was prolonged by the administration of tacrolimus-loaded microspheres. The microsphere formulation of tacrolimus would be expected to precisely control the blood concentration while maintaining the immunosuppressive effect of the drug.


Drug Development and Industrial Pharmacy | 2013

Effect of aminoalkyl methacrylate copolymer E/HCl on in vivo absorption of poorly water-soluble drug.

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

This study aimed to investigate in vivo absorption of tacrolimus formulated as a solid dispersion using Eudragit E®/HCl (E-SD). E-SD is an aminoalkyl methacrylate copolymer that can be dissolved under neutral pH conditions. E-SD was used alone as a solid dispersion carrier and/or was mixed with tacrolimus primarily dispersed with hydroxypropylmethylcellulose (HPMC). Tacrolimus was formulated with E-SD at several different ratios. Formulations with tacrolimus/E-SD ratio of 1/3 showed higher in vivo absorption, compared to tacrolimus dispersed in the excipients (primarily HPMC) found in commercially available tacrolimus capsules, using a rat in situ closed loop method. Good correlation was observed between in vitro drug solubility and in vivo drug absorption. In vitro solubility tests and rat oral absorption studies of tacrolimus/HPMC solid dispersion formulations were also conducted after mixing the HPMC dispersion with several ratios of E-SD. E-SD/tacrolimus/HPMC formulations yielded high in vitro drug solubility but comparatively low in vivo absorption. Dog oral absorption studies were conducted using capsules containing a formulation of tacrolimus/E-SD at a ratio of 1/5. The E-SD formulation-containing capsule showed higher in vivo drug absorption than tacrolimus dispersed in the standard HPMC capsule. These studies report enhancement of the in vivo absorption of a poorly water-soluble drug following dispersion with E-SD when compared to formulation in HPMC.


Archive | 2005

Stable granular pharmaceutical composition of solifenacin or its salt

Hiroyuki Umejima; Hiroshi Ohi; Katsumi Saito; Yuko Taketani


Archive | 2005

Stable Particular Pharmaceutical Composition of Solifenacin or Salt Thereof

Hiroyuki Umejima; Hiroshi Ohi; Katsumi Saito; Yuko Taketani


Archive | 2007

SOLID PHARMACEUTICAL COMPOSITION FOR ORAL ADMINISTRATION COMPRISING OPTICALLY STABLE RAMOSETRON

Hiroyuki Umejima; Ippei Kurimoto; Atsushi Kanbayashi; Chieko Mori


Archive | 2007

Aminoalkylmethacrylate copolymer e for maintaining solubility of poorly water-soluble drug

Takatsune Yoshida; Keiichi Yoshihara; Hiroyuki Umejima; Ippei Kurimoto


Archive | 2007

LIGHT-STABLE SOLID PHARMACEUTICAL COMPOSITION OF RAMOSETRON

Hiroyuki Umejima; Ippei Kurimoto; Atsushi Kanbayashi; Chieko Mori


Archive | 2009

Solid pharmaceutical composition for optically stable ramosetron

Hiroyuki Umejima; Ippei Kurimoto; Atsushi Kanbayashi; Chieko Mori

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