Amorphous solid dispersion of cyclosporine A prepared with fine droplet drying process: Physicochemical and pharmacokinetic characterization
| Autor: | Hideyuki Sato, Tadahiko Morinaga, Hiroki Suzuki, Yoshiki Seto, Tatsuru Moritani, Satomi Onoue |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Chemistry Pharmaceutical Administration Oral Biological Availability Pharmaceutical Science 02 engineering and technology Absorption (skin) behavioral disciplines and activities 030226 pharmacology & pharmacy Dioxanes Rats Sprague-Dawley 03 medical and health sciences Crystallinity 0302 clinical medicine Drug Stability Pharmacokinetics mental disorders Animals Technology Pharmaceutical Dissolution testing Particle Size Solubility Chromatography Chemistry 021001 nanoscience & nanotechnology Rats Amorphous solid Bioavailability Cyclosporine Particle size Powders 0210 nano-technology |
| Zdroj: | International Journal of Pharmaceutics. 519:213-219 |
| ISSN: | 0378-5173 |
| Popis: | The present study aimed to develop an amorphous solid dispersion (ASD) of cyclosporine A (CsA) by a fine droplet drying (FDD) process for improvement in oral absorption of CsA. CsA and hydroxypropyl cellulose-SSL were dissolved in 1,4-dioxane, and the solution was powdered by the FDD process to obtain the ASD formulation of CsA (ASD/CsA). The ASD/CsA was characterized in terms of morphology, particle size distribution, crystallinity, dissolution behavior, physicochemical stability, and pharmacokinetic behavior in rats. The ASD/CsA was obtained in the form of uniform spherical particles, and the span factor was calculated to be ca. 0.4. CsA in the formulation existed in an amorphous state. The ASD/CsA exhibited a higher dissolution behavior of CsA than amorphous CsA, whereas storage of the ASD/CsA under accelerated conditions led to impairment in the dissolution behavior. The constant release of CsA from non-aged ASD/CsA was observed during dissolution testing. After oral administration of CsA samples (10mg-CsA/kg) in rats, the ASD/CsA showed a high and sustained plasma concentration of CsA as evidenced by a 18-fold increase in the oral bioavailability of CsA compared with amorphous CsA. From these findings, the FDD process might be an efficacious option for the ASD formulation of CsA with enhanced biopharmaceutics properties. |
| Databáze: | OpenAIRE |
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