The elucidation of key factors for oral absorption enhancement of nanocrystal formulations: In vitro–in vivo correlation of nanocrystals
| Autor: | Yuichi Tozuka, Naomi Tamura, Shiro Miyazaki, Kazunori Kadota, Hidekazu Tsutsumimoto, Shinpei Yoshida, Masaaki Imono, Hiromasa Uchiyama |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Drug Compounding Administration Oral Pharmaceutical Science 02 engineering and technology Absorption (skin) 030226 pharmacology & pharmacy Permeability 03 medical and health sciences 0302 clinical medicine Fenofibrate In vivo Animals Intestinal Mucosa Particle Size In vitro in vivo Solubility Chemistry Megestrol Acetate General Medicine 021001 nanoscience & nanotechnology Rats Drug Liberation Key factors Intestinal Absorption Nanocrystal Chemical engineering Permeability (electromagnetism) Nanoparticles Particle 0210 nano-technology Biotechnology |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 146:84-92 |
| ISSN: | 0939-6411 |
| Popis: | Nanocrystal formulation is a well-established approach for improving oral absorption of poorly water-soluble drugs. However, it is difficult to predict the in vivo performance of nanocrystal formulations from in vitro dissolution studies. The object of the present study was to investigate the in vitro-in vivo correlation of nanocrystal formulations of different particle sizes. A microsuspension and three nanosuspensions with different particle sizes for model drugs, fenofibrate and megestrol acetate, were prepared. In the comparison between the microsuspension and the nanosuspension having the smallest particle sizes, drug permeation rates from the nanosuspension were about 3-fold higher in the dissolution-permeation study. On the other hand, the solubility enhancement effect due to nanocrystal formation was only up by 1.4-fold, suggesting that nanocrystal formulations dramatically improved not the solubility but the apparent permeability. The oral absorption rate in rats increased with particle size reduction. There were positive and very strong correlations (R2 > 0.95) between the in vitro permeation rate and in vivo maximum absorption rate. We concluded that the enhanced permeability rate due to nanocrystal formation is the main factor for improving oral absorption, and the in vitro dissolution-permeation study could be useful for predicting oral absorption enhancement of nanocrystal formulations. |
| Databáze: | OpenAIRE |
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