他克莫司口服自微乳骨架缓释微丸的制备及其释药机制研究

目的 制备他克莫司自微乳骨架缓释微丸，并探讨其释药机制。方法 采用星点设计-效应面法筛选他克莫司自微乳最优处方，在此基础上，采用挤出滚圆技术，以微晶纤维素(microcrystalline cellulose，MCC)为吸附剂和填充剂、乙基纤维素(ethyl cellulose，EC)与硬脂酸(stearic acid，SA)为骨架材料，以5%羟丙基甲基纤维素(hypromellose，HPMC)溶液为黏合剂，制备他克莫司自微乳骨架缓释微丸，并考察其体外溶出情况。结果 他克莫司自微乳最优处方为Crodamol EO∶Solutol HS15∶Transcutol P=15%∶52.5%∶32.5%。骨架缓释微丸最优处方为MCC用量为45%，EC∶SA用量比为3∶2，5%HPMC溶液用量为12 mL。制得的他克莫司自微乳骨架缓释微丸符合市售他克莫司缓释胶囊的体外释放标准，释药机制为溶蚀与扩散相结合。结论 优选的处方稳定可行，他克莫司自微乳骨架缓释微丸体外释放符合预期目的。

Preparation and Release Mechanism of Tacrolimus Oral Self-microemulsion Matrix Sustained-release Pellets

ABSTRACT: OBJECTIVE Tacrolimus self-microemulsion Matrix sustained-release pellets were prepared and the release mechanism was investigated. METHODS The optimal formulation of tacrolimus self-microemulsion was screened by star point design-response surface method, On this basis, tacrolimus self-microbe was prepared by extrusion spheronization technology with microcrystalline cellulose (MCC) as adsorbent and filler, ethyl cellulose (EC) and stearic acid (SA) as skeleton materials. Milk matrix sustained-release pellets, and their in vitro dissolution was investigated. RESULTS The optimal formula of tacrolimus self-microemulsion is EO:Solutol HS15:Transcutol P=20%:60%:20%. Tacrolimus self-microemulsion matrix sustained-release pellets meet the in vitro release standards of commercially available tacrolimus sustained-release capsules, and the release mechanism is a combination of erosion and diffusion. CONCLUSION The preferred formulation is stable and feasible, and the in vitro release of tacrolimus from microemulsion matrix sustained-release pellets meets the intended purpose.