Effect of aminoalkyl methacrylate copolymer E/ HCl onin vivoabsorption of poorly water-soluble drug
| Autor: | Takatsune Yoshida, Akihiko Kikuchi, Keiichi Yoshihara, Hiroyuki Umejima, Shunsuke Watanabe, Kazuhiro Sako, Ippei Kurimoto, Naoki Ito |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Absorption (pharmacology) Drug Compounding Administration Oral Biological Availability Pharmaceutical Science Capsules chemical and pharmacologic phenomena Methylcellulose Tacrolimus Intestinal absorption Excipients Rats Sprague-Dawley Dogs Hypromellose Derivatives In vivo Drug Discovery Animals Methylmethacrylates Solubility Pharmacology Drug Carriers Supersaturation Chromatography Chemistry Organic Chemistry Rats body regions surgical procedures operative Intestinal Absorption Indicators and Reagents Hydrochloric Acid Powders Dispersion (chemistry) Hydrophobic and Hydrophilic Interactions Immunosuppressive Agents Animals Inbred Strains |
| Zdroj: | Drug Development and Industrial Pharmacy. 39:1698-1705 |
| ISSN: | 1520-5762 0363-9045 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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