Studies on sirolimus self-microemulsifying drug delivery system and its solidification
-
摘要: 目的 筛选西罗莫司自微乳给药系统处方,并制备微丸。 方法 通过溶解度试验确定助乳化剂、油相和乳化剂的选择范围;采用三元相图法、星点设计和效应面法对该体系优化制备工艺及处方。采用挤出-滚圆法制备不同处方的西罗莫司自微乳化微丸。 结果 西罗莫司自微乳微丸的最终处方为:西罗莫司0.4%、油酸聚乙二醇甘油酯9.3%、聚氧乙烯-35-蓖麻油15.9%、二乙二醇单乙基醚8.0%、微晶纤维素49.8%、乳糖13.3%、羧甲基淀粉钠3.3%。溶出度试验显示,西罗莫司固体自微乳微丸在水中的溶出度远大于市售西罗莫司片,在0.4%SDS溶液中,两制剂的溶出度相当。 结论 自微乳化给药系统可用于提高西罗莫司的体外溶出度。Abstract: Objective To screen the formulation of self-microemulsifying drug delivery system(SMEDDS) for sirolimus(SRL) and prepare the SRL-SMEDDS pellets. Methods Co-emulsifier, oil phase and emulsifier were chosen by solubility test and ternary phase diagrams, central composite design and response surface method were adopted to screen and optimize the preparation and formulation of liquid SRL-SMEDDS. The selected liquid SRL-SMEDDS formulations were prepared into pellets by extrusion-spheronization method. Results The final pellets from liquid SRL-SMEDDS formulation:SRL 0.4%, Labrafil M1944CS 9.3%, Cremophor EL 15.9%, Transcutol P 8.0%, MCC 49.8%, lactose 13.3%, CMS-Na 3.3%. Dissolution test showed superphosphate(SSP) in the dissolution water is much greater than the commercially available sirolimus tablets; while in 0.4% SDS solution, the two formulations showed similar dissolution. Conclusion SMEDDS can improve the dissolution of SRL in vitro.
-
[1] Rial MC,Abbud-Filho M,Goncalves RT,et al. Individualizing early use of sirolimus in renal transplantation[J]. Transplant Proc,2010,42(10):4518-4525. [2] Toso C,Merani S,Bigam DL,et al. Sirolimus-based immunosuppression is associated with increased survival after liver transplantation for hepatocellular carcinoma[J].Hepatology,2010,51(4):1237-1243. [3] Chatel MA,Larkin DF. Sirolimus and mycophenolate as combination prophylaxis in corneal transplant recipients at high rejection risk[J]. Am J Ophthalmol,2010,150(2):179-184. [4] Chen Y,Li G,Wu X,et al. Self-microemulsifying drug delivery system(SMEDDS)of vinpocetine:formulation development and in vivo assessment[J]. Biol Pharm Bull,2008,31(1):118-125. [5] Patel AR,Vavia PR. Preparation and in vivo evaluation of SMEDDS(self-microemuldifying drug delivery system)containing fenofibrate[J].AAPS J,2007,9(3):344-352. [6] Woo JS,Song YK,Hong JY,et al. Reduced food-effect and enhanced bioavailability of a self-microemulsifying formulation of itraconazole in healthy volunteers[J]. Eur J Pharm Sci,2008,33(2):159-165. [7] 温许,黄爱文,张敏新,等. 西罗莫司固体自微乳口服缓释微丸的制备与体外释药考察[J]. 中国医院药学杂志,2014,34(23):1998-2003. -
点击查看大图
计量
- 文章访问数: 3299
- HTML全文浏览量: 370
- PDF下载量: 13
- 被引次数: 0
下载:
