他克莫司软膏的制备及体外经皮渗透评价

目的 研制与原研制剂经皮渗透性能一致的他克莫司软膏。方法 用LC-MS/MS测定样品中他克莫司的含量；以剪切应力、复合黏度等流变性参数和累积释放量为指标，筛选他克莫司软膏处方；采用改良Franz扩散池，以小型猪皮肤为渗透屏障，研究他克莫司软膏的经皮渗透性能。结果 自制他克莫司软膏的剪切应力(剪切速率：30 s^-1)为145.8 Pa、复合黏度为16.11 Pa·s、释放速率为(1 400±243)ng·cm^-2·h^-1/2、经皮渗透速率为(40.28±3.11)ng·cm^-2·h^-1、皮肤内滞留量为(9.515±1.096)ng·mg^-1；原研制剂的剪切应力(剪切速率：30 s^-1)为141.8 Pa、复合黏度为15.88 Pa·s、释放速率为(1 243±133)ng·cm^-2·h^-1/2、经皮渗透速率为(37.61±9.09)ng·cm^-2·h^-1、皮肤内滞留量为(8.463±1.770)ng·mg^-1。结论 自制他克莫司软膏与原研制剂的流变性和释放速率相似，经皮渗透性无显著性差异。

Preparation and in Vitro Evaluation of Percutaneous Permeability of Tacrolimus Ointment

OBJECTIVE To develop tacrolimus ointment with the same transdermal permeability as the original preparation. METHODS The content of tacrolimus was determined by LC-MS/MS. Theological parameters(shear stress, compound viscosity, and etc.) and cumulative release amount of tacrolimus ointment were used as the evaluation index to screen the formulation of tacrolimus ointment. The improved Franz diffusion cells and the skin of miniature pig were used to investigate the percutaneous permeability of tacrolimus ointment. RESULTS The self-made tacrolimus ointment and original preparation had shear stress(shear velocity:30 s^-1) of 145.8, 141.8 Pa, compound viscosity of 16.11 and 15.88 Pa·s, release velocity of (1 400±243)ng·cm^-2·h^-1/2 and (1 243±133)ng·cm^-2·h^-1/2, percutaneous penetration velocity of (40.28±3.11)ng·cm^-2·h^-1and (37.61±9.09)ng·cm^-2·h^-1, residue in skin of (9.515±1.096)ng·mg^-1 and (8.463±1.770)ng·mg^-1, respectively. CONCLUSION There is no significant difference in the rheology, release velocity, and transdermal permeability between the self-made tacrolimus ointment and the original preparation.