麻黄软胶囊的溶出稳定性及影响因素考察

目的：考察中药麻黄软胶囊的溶出稳定性及影响因素，探讨中药软胶囊溶出迟缓机制。方法：采用加速试验，评价麻黄软胶囊的溶出稳定性；以平衡溶胀量和ε-氨基酸残基含量为指标，评价明胶囊壳的交联程度；应用红外光谱和醛类专属反应，鉴定麻黄提取物中醛类成分，并测定其含量。结果：在加速试验条件下（40℃，75％相对湿度），放置30天后，明胶囊壳的平衡溶胀量和ε-氨基酸残基含量均显著下降（P〈0．01），其交联度显著增加（P〈0．01）；放置60天后，麻黄软胶囊溶出度显著下降（P〈0．01）。环境因素（高温／高湿）、溶媒介质（聚乙二醇）和药物成分（麻黄提取物）均可导致明胶交联度显著提高（P〈0．01），其中麻黄提取物的作用明显大于另两种影响因素。麻黄提取物中醛质量分数达约1．6％。结论：麻黄软胶囊溶出迟缓与囊壳明胶发生交联反应有关，而麻黄提取物中醛类成分是促进软胶囊发生交联反应、导致其溶出迟缓的主要原因。

Investigation on Dissolution Stability of Ephedra Extraction Soft Capsules and the Influence Factors Thereof

Objective： To investigate the dissolution stability of Ephedra extraction soft capsules and the influence factors thereof and to explore the mechanism of delayed dissolution of traditional Chinese medicine soft capsules. Methods： The dissolution stability of the prepared Ephedra extraction soft capsules was examined by accelerated test（40 ℃ and 75%RH）, the degree of crosslinking（D＇） of gelatin capsule shells was measured by equilibrium swelling quantity （Seq） and e-amino group content （CAA） as the crosslinking indexes, and the identification and content determination of aldehydes in Ephedra extraction were conducted by and CAA values of IR spectrum and other aldehyde-specific reactions. Results： In accelerated test, the S,q gelatin capsule shells decreased significantly （P 〈0.01） and their D＇ values increased significantly （P 〈0.01） after 30 d, and the dissolution rate of the capsules decreased significantly （P 〈 0.01） after 60d. Higher temperature and humidity, PEG 400 and Ephedra extraction promoted significantly the gelatin crosslinking （P 〈 0.01）, where the effect of Ephedra extraction was more significant than that of others. The content of aldehydes in Ephedra extraction was about 1.6%. Conclusion： The delayed dissolution of Ephedra extraction soft capsules is related to the gelatin crosslinking. Aldehydes in Ephedra extraction are the main cause for the gelatin crosslinking and the delayed dissolution of the soft cansules.