Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit® E
The present study aimed to investigate the effect of Eudragit® E/HCl (E-SD) on the degradation of sirolimus in simulated gastric fluid (pH 1.2) and to develop a new oral formulation of sirolimus using E-SD solid dispersions to enhance oral bioavailability. Sirolimus-loaded solid dispersions were fab...
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| Format: | Article |
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MDPI AG
2015-05-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/20/6/9496 |
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| author | Youngseok Cho Eun-Sol Ha In-Hwan Baek Min-Soo Kim Cheong-Weon Cho Sung-Joo Hwang |
| author_facet | Youngseok Cho Eun-Sol Ha In-Hwan Baek Min-Soo Kim Cheong-Weon Cho Sung-Joo Hwang |
| author_sort | Youngseok Cho |
| collection | DOAJ |
| description | The present study aimed to investigate the effect of Eudragit® E/HCl (E-SD) on the degradation of sirolimus in simulated gastric fluid (pH 1.2) and to develop a new oral formulation of sirolimus using E-SD solid dispersions to enhance oral bioavailability. Sirolimus-loaded solid dispersions were fabricated by a spray drying process. A kinetic solubility test demonstrated that the sirolimus/E-SD/TPGS (1/8/1) solid dispersion had a maximum solubility of 196.7 μg/mL within 0.5 h that gradually decreased to 173.4 μg/mL after 12 h. According to the dissolution study, the most suitable formulation was the sirolimus/E-SD/TPGS (1/8/1) solid dispersion in simulated gastric fluid (pH 1.2), owing to enhanced stability and degree of supersaturation of E-SD and TPGS. Furthermore, pharmacokinetic studies in rats indicated that compared to the physical mixture and sirolimus/HPMC/TPGS (1/8/1) solid dispersion, the sirolimus/E-SD/TPGS (1/8/1) solid dispersion significantly improved oral absorption of sirolimus. E-SD significantly inhibited the degradation of sirolimus in a dose-dependent manner. E-SD also significantly inhibited the precipitation of sirolimus compared to hydroxypropylmethyl cellulose (HPMC). Therefore, the results from the present study suggest that the sirolimus-loaded E-SD/TPGS solid dispersion has great potential in clinical applications. |
| first_indexed | 2024-12-12T20:32:14Z |
| format | Article |
| id | doaj.art-262d406a7fc54c4cb68e3b0ed974f382 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-12T20:32:14Z |
| publishDate | 2015-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-262d406a7fc54c4cb68e3b0ed974f3822022-12-22T00:12:59ZengMDPI AGMolecules1420-30492015-05-012069496950910.3390/molecules20069496molecules20069496Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit® EYoungseok Cho0Eun-Sol Ha1In-Hwan Baek2Min-Soo Kim3Cheong-Weon Cho4Sung-Joo Hwang5College of Pharmacy, Chungnam National University, Daejeon 305-764, KoreaCollege of Pharmacy, Pusan National University, Busan 609-735, KoreaCollege of Pharmacy, Kyungsung University, Busan 608-736, KoreaCollege of Pharmacy, Pusan National University, Busan 609-735, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 305-764, KoreaCollege of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 406-840, KoreaThe present study aimed to investigate the effect of Eudragit® E/HCl (E-SD) on the degradation of sirolimus in simulated gastric fluid (pH 1.2) and to develop a new oral formulation of sirolimus using E-SD solid dispersions to enhance oral bioavailability. Sirolimus-loaded solid dispersions were fabricated by a spray drying process. A kinetic solubility test demonstrated that the sirolimus/E-SD/TPGS (1/8/1) solid dispersion had a maximum solubility of 196.7 μg/mL within 0.5 h that gradually decreased to 173.4 μg/mL after 12 h. According to the dissolution study, the most suitable formulation was the sirolimus/E-SD/TPGS (1/8/1) solid dispersion in simulated gastric fluid (pH 1.2), owing to enhanced stability and degree of supersaturation of E-SD and TPGS. Furthermore, pharmacokinetic studies in rats indicated that compared to the physical mixture and sirolimus/HPMC/TPGS (1/8/1) solid dispersion, the sirolimus/E-SD/TPGS (1/8/1) solid dispersion significantly improved oral absorption of sirolimus. E-SD significantly inhibited the degradation of sirolimus in a dose-dependent manner. E-SD also significantly inhibited the precipitation of sirolimus compared to hydroxypropylmethyl cellulose (HPMC). Therefore, the results from the present study suggest that the sirolimus-loaded E-SD/TPGS solid dispersion has great potential in clinical applications.http://www.mdpi.com/1420-3049/20/6/9496sirolimussupersaturationbioavailabilityEudragit® Esolid dispersion |
| spellingShingle | Youngseok Cho Eun-Sol Ha In-Hwan Baek Min-Soo Kim Cheong-Weon Cho Sung-Joo Hwang Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit® E Molecules sirolimus supersaturation bioavailability Eudragit® E solid dispersion |
| title | Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit® E |
| title_full | Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit® E |
| title_fullStr | Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit® E |
| title_full_unstemmed | Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit® E |
| title_short | Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit® E |
| title_sort | enhanced supersaturation and oral absorption of sirolimus using an amorphous solid dispersion based on eudragit r e |
| topic | sirolimus supersaturation bioavailability Eudragit® E solid dispersion |
| url | http://www.mdpi.com/1420-3049/20/6/9496 |
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