壬二酸凝胶的制备与质量控制

Preparation and quality control of azelaic acid gel

目的探讨壬二酸凝胶稳定性新剂型的制备工艺,并开展质量控制研究。方法加入非离子型增溶剂聚氧乙烯蓖麻油EL制备壬二酸凝胶,建立鉴别、检查、含量测定等质量控制方法,研究了一种柱前管路高效液相色谱法测定壬二酸含量的方法。通过离心试验、耐寒耐热试验、加速试验、长期试验考察壬二酸凝胶的稳定性。结果壬二酸凝胶鉴别、检查、含量测定均符合《中华人民共和国药典》2015年版凝胶剂的规定;壬二酸在0.100~6.400mg/mL浓度范围内呈良好的线性关系,r=0.9999;平均回收率为99.4%(n=9,RSD=0.55%);金黄色葡萄球菌、铜绿假单胞菌、枯草芽孢杆菌、白色念珠菌和黑曲霉5个菌株3次试验的回收率均在0.5~2.0。经离心试验、耐热耐寒试验、加速试验、长期试验考察壬二酸凝胶无分层和破乳,含量和微生物限度在12个月内符合质量标准。结论新剂型壬二酸凝胶制备工艺可行,质量稳定可控,为开发壬二酸凝胶提供理论基础。

Objective To explore the preparation technology of a new stable formulation of azelaic acid(AzA)gel and to carry out quality control research.Methods The non-ionic solubilizer polyoxyethylene castor oil EL was added to prepare AzA gel,and quality control methods such as identification,inspection and content determination were established.A method for determination of AzA content by pipeline before column high-performance liquid chromatography was studied.The stability of AzA gel was investigated by centrifugal test,cold and heat resistance test,accelerated test and long-term test.Results The identification,examination and content determination of AzA gel revealed the accordance with the regulations of Pharmacopoeia of The People's Republic of China 2015 on gelata;azelaic acid showed a good linear relationship in the concentration range of 0.100-6.400mg/mL,and r=0.9999;the average recovery rate was 99.4%(n=9,RSD=0.55%);The recovery rate of the 5 strains of staphylococcus aureus,pseudomonas aeruginosa,bacillus subtilis,candida albicans and aspergillus niger in 3 tests kept being within the range of 0.5-2.0.Through centrifugal test,heat and cold resistance test,accelerated test and long-term test,it was proved that AzA gel had neither delamination nor demulsification,and its content and microbial limit met the quality standard within 12m.Conclusion The preparation process of a new formulation of AzA gel is feasible and its quality could be stable and controllable,which provides a theoretical basis for the development of AzA gel.