Study on sirolimus solubilization technology based on in vitro dissolution and in vivo bioavailability
10.12206/j.issn.1006-0111.201910022
- VernacularTitle:基于体外溶出度与体内生物利用度的西罗莫司增溶技术研究
- Author:
Xueting ZHANG
1
,
2
;
Chao YUN
1
,
2
;
Zhenzhen CHEN
1
,
2
;
Chun TAO
3
;
Hongtao SONG
3
Author Information
1. Department of Pharmacy, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou 350025, China
2. College of Pharmacy, Fujian Medical University, Fuzhou 350108, China.
3. Department of Pharmacy, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou 350025, China.
- Keywords:
sirolimus;
solid dispersion;
inclusion complex;
SMEDDS;
nano-structured lipid carrier;
dissolution;
bioavailability
- From:
Journal of Pharmaceutical Practice
2020;38(5):441-446
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effects of different solubilizing techniques on the in vitro dissolution and in vivo pharmacokinetics of Sirolimus (SRL). Methods Solid dispersions (SD), inclusion complex (IC), self-micro emulsifying drug delivery system (SMEDDS) and nano-structured lipid carrier (NLC) were selected as the solubilization technology for SRL. SRL-SMEDDS and SRL-NLC have obtained the optimal prescription in the previous studies. Additionally, the formulation process of SRL-SD and SRL-IC was screened by using inclusion rate and dissolution profiles as indicators. 0.4% SDS, water and buffer solutions with pH 1.2, 4.5, 6.8, 7.4 were used as dissolution media. The dissolution profile of the commercially available formulation Rapamune® and the lab-made solubilized preparations were investigated. The in vivo absorption of the above preparations was examined using a pharmacokinetic test in Beagle dogs. Results In 0.4% SDS, the dissolution of each preparation exceeded 80% in 2 h. In the medium of pH 1.2, the dissolution of SRL-SD could not be measured while the dissolution of IC, SMEDDS and NLC increased first and then decreased. In other media, the dissolution of the SRL was reduced. The SRL-IC showed the best dissolution without a significant decrease. The relative bioavailability of APIs, SRL-SD, SRL-IC, SRL-NLC and SRL-SMEDDS were 9.1%, 18.7%, 33.2%, 78.0%, and 97.6% respectively in vivo pharmacokinetic tests. Conclusion SD, SMEDDS, NLC, and IC can improve the in vitro dissolution and in vivo absorption of SRL. Among them, SMEDDS has the most significant improvement in the bioavailability of SRL.
