摘要
药物辅料筛选和处方优化在药物的稳定性和药效表达方面具有重要的意义。但传统的处方设计主要局限在模仿上市产品、采用经验处方或正交试验摸索处方等方面,缺少分子水平上解释和严谨的理论依据。本文通过分子模拟技术研究了分子调控技术在奥拉西坦冻干粉针剂最佳药物辅料筛选和优化药物处方上的可行性。研究结果表明海藻糖的吸附作用最大,次之是山梨醇,二者对奥拉西坦晶体生长的分子调控结果较好;其次,在奥拉西坦溶液中,海藻糖、甘油和山梨醇对奥拉西坦传质的分子调控最大。综合评价来看,山梨醇对奥拉西坦整个结晶过程的分子调控最大,效果最佳。同时,通过分子模拟技术研究分子调控方法筛选最佳药物辅料和优化药物处方比传统上试错重复的实验模式更快捷高效和透彻。
It is vital significant of the excipicnt screening and optimization in terms of the pharmaceutical stability and efficacy. However, the traditional formulation design usually focus on imitation of the listed products, copying empirical formulation, orthogonal experiments, which still lacks of rigorous theoretical explanation at the molecular level. Therefore, the drug excipient screening and formulation optimization of oxiracetam lyophilized powder for injection were investigated by using molecular simulation technology with molecular regulation theory. Research results show that the adsorption effect of trehalose is more obvious, next is sorbitol. The molecular regulation of both excipients for oxiracetam crystal growth is better. For oxiracetam aqueous solution, the molecular regulation of trehalose, glycerol and sorbitol for oxiracetam mass transfer is better. Summarily, the effect of sorbitol on whole crystallization process of oxiracetam is best. And comparing with traditional trial-and-error experimental model, molecular simulation is a quick and efficient and thorough technology to research drug excipient screening and formulation optimization.
出处
《计算机与应用化学》
CAS
2015年第9期1149-1152,共4页
Computers and Applied Chemistry
基金
上海市2012年度"科技创新行动计划"国际科技合作项目(12430702000)
上海市自然科学基金项目(12ZR1420400)
上海市教委创新项目(14YZ092)
关键词
分子调控
分子模拟
结晶过程控制
奥拉西坦
药物辅料筛选
处方优化
molecular regulation
molecular simulation
crystallization process control
S-oxiracetam
drug excipient screening
formulation optimization
