基于盐酸度洛西汀肠溶微丸的原研及仿制胶囊剂的稳定性考察

Stability Investigation of Innovator and Generic Capsules Based on Duloxetine Hydrochloride Enteric Pellets

考察了基于盐酸度洛西汀肠溶微丸的3种胶囊剂[原研制剂欣百达？,以醋酸羟丙甲基纤维素琥珀酸酯（HPMCAS）为肠溶包衣材料,以及2种仿制制剂（分别以HPMCAS和甲基丙烯酸树脂Eudragit L30D-55为肠溶包衣材料）]在加速试验（40℃、相对湿度75%）中的稳定性。将3种胶囊剂分别于加速条件放置6个月,考察试验期间3种制剂的药物含量、微丸尺寸和形态以及释放特性稳定性。结果显示,原研制剂及2种仿制制剂在加速试验期间药物含量均大于95%、微丸尺寸和形态无明显变化,提示两种肠溶材料均与药物有良好的化学相容性,物理性质稳定;但采用Eudragit L30D-55的仿制制剂2中药物含量在6个月时有轻微下降。通过相似因子（？2）判断,3种制剂在加速试验期间药物释放特性保持稳定,但仿制制剂2在p H 6.8磷酸盐缓冲溶液中释放不完全。因此,本试验提示在开发高质量盐酸度洛西汀肠溶微丸仿制制剂中HPMCAS是更好的肠溶辅料。

An accelerated test at 40 ℃ and relative humidity of 75 % was carried out to investigate the stabilities of three types of capsules based on duloxetine hydrochloride enteric pellets, which were innovator preparation Cymbalta with hypromellose acetate succinate （HPMCAS） as an enteric coating material and two generic preparations with HPMCAS and polyacrylic resin Eudragit L30D-55 as enteric coating materials. During the 6 months＇ testing at the accelerated storage, the drug content, particle size and morphology of enteric pellets and release stability of three types of capsules were determined. The results showed that the measured drug content of innovator and generic capsules were all above 95 % and there were no significant changes in particle size and shape of the enteric pellets during the accelerated test, which indicated that both enteric polymers were chemically compatible with duloxetine hydrochloride and the enteric pellets were physically robust. However, the drug content in ＂generic capsules 2＂, which contained duloxetine hydrochloride enteric pellets with Eudragit L30D-55 as an enteric coating material was slightly decreased at the sixth month. According to the results of similarity factor （f2）, the release profiles of three types of capsules remained stable throughout the accelerated storage. But the drug release from generic capsules 2 was not completely in pH 6.8 phosphate buffer. Thus it was concluded that HPMCAS was a better choice as an enteric polymer for development of high-quality generics （enteric pellet formulation）.