秋水仙碱2种醇质体贴剂的制备及其质量评价

Preparation and quality evaluation of two types of colchicine ethosome patches

目的采用均匀设计法优化2种秋水仙碱醇质体贴剂制备处方并考察其体外释放度、透皮性能、稳定性及其刺激性。方法采用注入法分别制备2种磷脂材料(大豆磷脂和氢化磷脂)的秋水仙碱醇质体;通过DPS 7.0软件分析,采用均匀设计法,以初黏力与持黏力的综合评分为考察指标优化贴剂压敏胶中秋水仙碱、IV号丙烯酸树脂、柠檬酸三乙酯、琥珀酸以及氮酮的组成,制备上述2种醇质体的贴剂;用智能溶出度测试仪和改良的Franz扩散池分别比较贴剂的释放度和透皮性能;考察制剂在光照、湿度和高温条件下的稳定性;进行兔皮肤的刺激性实验。结果通过均匀设计优化法制备的秋水仙碱醇质体贴剂,符合《中国药典》2010年版规定的贴剂黏性要求,秋水仙碱普通贴剂、大豆磷脂和氢化磷脂醇质体贴剂体外释放度拟合符合Higuchi方程,释放速率依次增加,分别为(3.133 1±0.327 2)、(2.872 4±0.348 1)、(2.380 2±0.213 4)μg/(cm2·h1/2),三者体外透皮速率符合零级方程,透皮率依次提高,分别为(0.939 0±0.073 1)、(0.877 5±0.090 8)、(0.616 7±0.081 6)μg/(cm2·h);氢化磷脂醇质体贴剂在保存期间稳定性考察指标变化均低于大豆磷脂醇质体贴剂,尤其是色泽稳定。兔皮肤刺激性试验48 h内无红斑、水肿等刺激反应。结论氢化磷脂醇质体贴剂药物释放度与透皮速率均明显最优,考虑到其较好的制剂稳定性,可见氢化磷脂醇质体贴剂综合性能明显优于大豆磷脂醇质体贴剂。

Objective To optimize the two types of colchicine ethosome patches using uniform design and to investigate their in vitrorelease, transdermal properties, stability, and stimulus. Methods Two kinds of colchicine ethosomes made of soybean lecithin （SL） and hydrogenated phosphatidy （HP） were prepared using injection method. By the DPS 7.0 software, the uniform design was used to optimize the patch components of colchicines, polyacrylic resin IV, succinic acid, triethyl citrate, and azone in patch pressure-sensitive adhesive, with its initial adhesion and hold tack as indexes. The colchicine ethosomes patches of SL and HP were prepared, respectively. The automated dissolution test analyzer and improved Franz diffusion cell were adopted to compare the in vitro release and transdermal properties of the two types of colchicine ethosomes patches, respectively. Moreover, the preparation stability under different light, humidity, and high temperature conditions was studied, and the skin irritation test for rabbits was carried out. Results The optimized colchicine ethosome patches by the uniform design adhere with the viscous standards in Chinese Pharmacopeia 2010. The in vitro release of the three types of patches were fitted with the Higuchi equation and their release rates increased in turn, respectively, which were （3.133 1 ± 0.327 2）, （2.872 4 ± 0.348 1）, and （2.380 2 ± 0.213 4） μg/（cm2.h^1/2）. Their in vitro transdermal releases were fitted with the zero-class equation and increased in turn, respectively, which were （0.939 0 ± 0.073 1）, （0.877 5 ± 0.090 8）, and （0.616 7 ± 0.081 6） μg/（cm2.h）. During the storage, the HP patches had better stability than the SL patches, especially with the stable color. In the skin irritation test for rabbits, there was no erythema and oedema reactions in 48 h. Conclusion The HP patches have obviously higer in vitro release rate and transdermal rate, and for its better stability of preparation, the HP patches are superior to the SL ones.