論文 - 詳細
| RRC ID | 45079 |
|---|---|
| 著者 | Onoue S, Suzuki H, Kojo Y, Matsunaga S, Sato H, Mizumoto T, Yuminoki K, Hashimoto N, Yamada S. |
| タイトル | Self-micellizing solid dispersion of cyclosporine A with improved dissolution and oral bioavailability. |
| ジャーナル | Eur J Pharm Sci |
| Abstract |
The present study aimed to develop a self-micellizing solid dispersion (SMSD) of cyclosporine A (CsA) using an amphiphilic block copolymer, poly[MPC-co-BMA], to improve the biopharmaceutical properties of CsA. The cytotoxicity of poly[MPC-co-BMA] was assessed in rat intestinal IEC-6 cells, and the pMB was less cytotoxic than polysorbate 80, a non-ionic surfactant with a wide safety margin. SMSD/CsA was prepared using a wet-milling system, and its physicochemical properties were characterized in terms of morphology, crystallinity, dissolution, particle size distribution, and stability. The SMSD/CsA exhibited immediate formation of fine micelles with a mean diameter of ca. 180 nm when introduced into aqueous media. There was marked improvement in the dissolution behavior of the SMSD/CsA compared with amorphous CsA. Even after storage at 40°C/75% relative humidity, the dissolution behavior of aged SMSD/CsA seemed to be almost identical to that of its freshly prepared equivalent, and CsA in aged SMSD/CsA was still in amorphous form. After oral administration of SMSD/CsA (10 mg CsA/kg) in rats, enhanced CsA exposure was observed with increases of Cmax and BA by ca. 11- and 42-fold, respectively, compared with those of amorphous CsA. The poly[MPC-co-BMA]-based SMSD formulation system might be an efficacious dosage option for CsA to achieve improvements in oral bioavailability. |
| 巻・号 | 62 |
| ページ | 16-22 |
| 公開日 | 2014-10-1 |
| DOI | 10.1016/j.ejps.2014.05.006 |
| PII | S0928-0987(14)00190-0 |
| PMID | 24836392 |
| MeSH | Animals Biological Availability Cell Line Cell Survival / drug effects Chemistry, Pharmaceutical Cyclosporine* / administration & dosage Cyclosporine* / blood Cyclosporine* / chemistry Cyclosporine* / pharmacokinetics Drug Stability Immunosuppressive Agents* / administration & dosage Immunosuppressive Agents* / blood Immunosuppressive Agents* / chemistry Immunosuppressive Agents* / pharmacokinetics Male Methacrylates / chemistry* Micelles* Phosphorylcholine / analogs & derivatives* Phosphorylcholine / chemistry Rats, Sprague-Dawley Solubility |
| IF | 3.616 |
| 引用数 | 21 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | |