尼莫地平软胶囊的稳定性和体内外相关性研究  

Stability and in vitro-in vivo correlation of nimodipine soft gelatin capsules

作　　者：卫世杰[1] 刘建平[1] 郑文杰[1] 逯睿[1] 

机构地区：[1]中国药科大学药物制剂研究所,南京210009

出　　处：《中国药科大学学报》2006年第3期233-237,共5页Journal of China Pharmaceutical University

基　　金：国家中医管理局资助项目(No.02-03ZL04)~~

摘　　要：目的:考察室温放置的尼莫地平软胶囊的稳定性及体外溶出与体内生物利用度之间的相关性。方法:分别对软胶囊的崩解时限、溶出度、平衡溶胀量、氨基酸残基含量和甲醛含量进行测定,并用HPLC法测定家兔口服软胶囊后的血药浓度,研究体外溶出度和体内生物利用度之间的相关性。结果:尼莫地平软胶囊在人工胃液中的崩解时限和溶出度(45 min)与在蒸馏水和盐酸溶液(9→1 000)相比有显著性或极显著性差异;氨基酸残基的含量、明胶的平衡溶胀量及甲醛含量与溶出度有良好的线性关系;放置12个月、18个月及24个月的软胶囊的cmax依次降低,tmax依次延长,但12个月、18个月软胶囊的AUC与新制软胶囊相比无显著差异;以人工胃液为介质的溶出度与体内生物利用度之间具有良好的相关性(r=0.992 5)。结论:尼莫地平软胶囊体外崩解时限和溶出度测定结果与实验所用的介质有关,以人工胃液为介质所得的溶出度与体内生物利用度之间有良好线性关系。Aim：To evaluate the stability of nimodipine soft gelatin capsules （SGC） and the correlation between in vitro dissolution and in vivo bioavailability. Methods： The disintegration time, dissolution, swelling equilibrium quantity （Seq）, formaldehyde content and amino acid residue content of nimodipine SGC stored in room temperature were analyzed after preplanned intervals. And the plasma concentration in rabbits was determined after po dosing of SGC containing nimodipine of 20 mg. Results： The disintegration time and dissolution profiles of nimodipine SGC in the stimulated gastric fluid were significantly different from those conducted in distilled water and HCI solution（9→1 000）. Amino acid residue, S^q and formaldehyde content were found to be correlated with the dissolution at 45 min. Following 12, 18 and 24 months storage, the magnitudes of Cmax, were sequentially decreased and those of tmax were increased. However, there are no marked changes to AUCs except that after 24 month storage. Correlation between the bioavailability of nimodipine SGC and its dissolution rate in stimulated gastric fluid occurred （ r = 0.992 5 ）. Conclusion： Results of disintegration and dissolution of nimodipine SGC could be dependent on the testing medium. Dissolution of nimodipine SGC in the stimulated gastric fluid proves to be related to in vivo bioavailability.

关 键 词：软胶囊 尼莫地平 稳定性 体内外相关性 

分 类 号：R927.11[医药卫生—药学] R96