钙离子通道阻滞剂自乳化给药系统的形成机理

Insight into the Formation Mechanisms Behind Self-emulsifying Drug Delivery Systems of Calcium Channel Blockers

以一系列难溶性的二氢吡啶类钙离子通道阻滞剂作为模型药物,以自乳化面积和药物在自乳化给药系统(SEDDS)中的溶解度作为自乳化评价指标,建立各组分的分子描述参数与自乳化性质之间的定量函数关系,通过模型讨论分子结构对自乳化形成机理的影响.结果表明,自乳化的发生是各组分含量、分子间作用力、亲脂性和分子大小等多方面因素综合作用的结果.当混合表面活性剂分子较大且药物脂溶性较好时,SEDDS对难溶性药物的增溶能力较强;表面活性剂与助表面活性剂的质量比较大,混合表面活性剂的分子较大时,SEDDS的稀释稳定性较好.

Several self-emulsifying drug delivery systems（ SEDDS） were constructed, using a series of poorly water-soluble dihydropyridines of calcium channel blockers（ DHPs-CCBs） as the model drugs, and characte- rized them with regards to self-emulsification area and solubility of the payloads. By establishing multiple linear regression（ MLR） models between the molecular descriptors of building components and characteristics of the emulsions formed eventually, we then tried to reveal the formation mechanisms under self-emulsification process. It was found that emulsification process was primarily initialized by the intermolecular forces but simultaneously affected by the proportion of components, lipophilicity and molecular size. Larger molecular size of the mixed surfactants and better lipophilicity of drug contributed to higher drug solubility. Also, the stability of SEDDS after dilution correlated positively with the mass ratio of surfactants and co-surfactants and the molecular size of mixed surfactants. It is supposed that this work could generally be used as guidelines to screen the formulas of SEDDS.