Preparation and evaluation of sirolimus sustained release tablets based on mesoporous silicon loaded self-microemulsion
10.16438/j.0513-4870.2022-1193
- VernacularTitle:基于介孔硅固化自微乳的西罗莫司缓释片的制备与评价
- Author:
Wen-ting HUANG
1
;
Zhi-hong LIU
2
;
Ling-na ZHANG
3
;
Ling-jun ZENG
2
;
Qian ZHANG
4
;
Hong-tao SONG
2
Author Information
1. 900TH Hospital of Joint Logistics Support Force, Fuzhou 350025, China; Department of Pharmacy, Fujian Medical University, Fuzhou 350108, China
2. 900TH Hospital of Joint Logistics Support Force, Fuzhou 350025, China
3. Fujian Medical Products Administration, Fuzhou 350003, China
4. Department of Pharmacy, Fujian Medical University, Fuzhou 350108, China
- Publication Type:Research Article
- Keywords:
sirolimus;
self-microemulsion;
mesoporous silicon;
sodium carboxymethyl starch;
hydroxypropyl methylcellulose;
sustained-release tablet
- From:
Acta Pharmaceutica Sinica
2023;58(4):1049-1058
- CountryChina
- Language:Chinese
-
Abstract:
Sirolimus self-microemulsion-mesoporous silicon sustained release tablets were prepared in order to improve the dissolution of the insoluble drug sirolimus and reduce its side effects. Firstly, sirolimus self-microemulsion was prepared and cured with mesoporous silicon. Secondly, the suitable excipients were selected according to the appearance, hardness and in vitro release rate. The sustained-release tablets with hydroxypropyl methylcellulose (HPMC) as skeleton material were prepared by powder direct pressing method, and the formulation was optimized by central composite design-response surface method to investigate the drug release in vitro. Finally, the pharmacokinetics was carried out in beagle dogs using the commercial sirolimus tablets as references. The final formulation of sustained-release tablets is as follows: 162 mg of sirolimus self-microemulsion-mesoporous silica (1∶1, w/w), 80 mg of HPMC K4M and 80 mg of carboxymethyl starch sodium, the microcrystalline cellulose is 168 mg. The results of in vitro release test showed that the self-made sustained-release tablets released slowly within 12 h, which conformed to the Ritger-Peppas model. The in vivo test results showed that compared with the commercial sirolimus tablets, the Cmax of the sustained-release tablets decreased by 49.47%, the Tmax of the sustained-release tablets was prolonged by 5.1 times, and the relative bioavailability was 105.81%. Sirolimus self-microemulsion-mesoporous silicon sustained-release tablets have good sustained-release effects in vitro and in vivo, which provides a reference for the solubilization of other insoluble drugs and the research and development of sustained-release preparations. Animal experiments and welfare processes were reviewed and approved by the Animal Ethics Committee of the 900TH Hospital of the Joint Logistics support Force.
