基于释药模型的他克莫司缓释微丸处方设计研究

Application of Drug Release Model in Design of Tacrolimus Sustained-Release Pellets Prescription

目的应用表面降解溶蚀释药模型,指导他克莫司缓释微丸的处方设计,提高设计的准确性和针对性。方法采用单纯形重心设计法,确立处方配比与表面降解速率常数K值的关系,建立起释药模型释放度预测与制剂处方的关联,根据预期的释放度要求,实现对处方设计的指导。并采用热熔包衣技术制备他克莫司缓释微丸,对模型预测和实验测定的释放曲线进行比较。结果测定和预测的释放曲线相似因子f2>75,释放度单点误差<5%。结论本实验所建模型,可根据释放度要求,快速、准确地指导他克莫司缓释微丸的处方设计。

OBJECTIVE To design tacrolimus sustained-release pellets formula by surface degradation and erosion model, and improve the design accuracy and pertinence. METHODS The relationship between the prescription and the surface degradation rate constant K was determined by simplex centroid design. The relationship between dissolution prediction and formulation was established and used to direct the formulation design according to the requirements of the expected dissolution. The dissolution profiles obtained by the model prediction and actual experiment were compared through hot-melt coating technology. RESULTS The dissolution profile similarity factorf2was over 75 between the measured and predicted dissolution profiles, and the single point error of dissolution was be- low 5%. CONCLUSION Using the established model, the formula of tacrolimus sustained-release pellets can be quickly and accu- rately designed according to the dissolution requirement.