胆芩温敏眼用凝胶的基质处方优化及其体外释放性能  

Prescription Optimization of Matrix Formulation of Danqin Thermosensitive Ophthalmic Gel and Its Release Properties In Vitro

作　　者：郭俊国 郭新苗[3] 王刚 宋继科 毕宏生[2,4] 田景振[1] GUO Junguo;GUO Xinmiao;WANG Gang;SONG Jike;BI Hongsheng;TIAN Jingzhen(College of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Department of Pharmacy,Eye Instituteof Shandong University of Traditional Chinese Medicine,Jinan 250002,China;School of Management,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Department of Experimental Center,Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250002,China)

机构地区：[1]山东中医药大学药学院,济南250355 [2]山东中医药大学眼科研究所药学室,济南250002 [3]山东中医药大学管理学院,济南250355 [4]山东中医药大学附属眼科医院实验中心,济南250002

出　　处：《医药导报》2021年第10期1391-1397,共7页Herald of Medicine

基　　金：山东省重点研发计划项目(2017GSF19110);国家自然科学基金面上项目(81873163,81674032);国家重点研发计划(2019YFC1710205);山东省中医药科技发展计划项目(2015-146)。

摘　　要：目的优选胆芩温敏眼用凝胶(DQTOG)的基质处方以确定其制备工艺,并考察体外溶蚀性和释药性。方法以相变温度(T gel)和人工泪液稀释后的相变温度(T atd gel)为考察指标,在单因素考察泊洛沙姆407(P407)、泊洛沙姆188(P188)和丙二醇(PGI)凝胶基质的基础上,采用星点设计-效应面法(CCD-RSM)3因素5水平优选基质处方,恒温振荡法考察体外溶蚀性,第二桨法考察黄芩苷和栀子苷的体外释药行为。结果P407浓度增加,其T gel和T atd gel逐渐下降;P188浓度增加,其T gel和T atd gel逐渐升高,低浓度的PGI可增加T gel和T atd gel。二项式拟合模型为最佳模型,最优基质处方:P407为24.5%,P188为6%,PGI为6%,预测T gel值24.7℃,T atd gel值34.4℃,3批工艺验证结果T gel值24.9℃,T atd gel值35.2℃,偏差绝对值均<3%。凝胶累积溶蚀量随平底试管截面面积的增加而增大,随震荡频率的增加而增大,符合零级动力学特征。黄芩苷和栀子苷均在300 min基本释药完全,累积释放率与转速有关,黄芩苷的体外释放符合一级方程,栀子苷的体外释放符合零级方程。结论星点设计-效应面法筛选胆芩温敏眼用凝胶的基质处方可较好地预测各因素和凝胶相变温度的关系,制备的胆芩温敏眼用凝胶体外具有良好的溶蚀性和释药性。Objective To optimize the matrix formulation of Danqin thermosensitive ophthalmic gel(DQTOG)to determine its preparation process,and to investigate its dissolution and release properties in vitro.Methods The phase transition temperature(T gel)and the temperature of dilation after artificial tears(T atd gel)were used to optimize the gel matrix of poloxamer 407(P407),poloxamer 188(P188)and propylene glycol(PGI).The gel matrix formulation was optimized by 3 factors and 5 levels of central composite design response surface method(CCD-RSD).The dissolution in vitro was examined by constant temperature,and the dissolution rate of baicalin and geniposide in vitro was investigated by second paddle method.Results With the concentration of P407 increased,the T gel and T atd gel gradually decreased.The concentration of P188 increased,the T gel and T atd gel gradually increased.The low concentration of PGI can increase the T gel and T atd gel.The binomial fitting model was the best model.The optimal matrix formula were 24.5%P407,6%P188 and 6%PGI.The predicted T gel and T atd gel were 24.7℃and 34.4℃,respectively.The predicted T gel and T atd gel were 24.9℃and 35.2℃by 3 batches process validation,and the deviation absolute value was less than 3%.The amount of gel cumulative dissolution were increased with the increasing of the cross section area of the flat bottom tube,and the amount of gel cumulative dissolution were increased with the increasing of the frequency of oscillation.Baicalin and gardenoside could be released completely in 300 min,and the cumulative release rate was related to the rotational speed.The release of baicalin in vitro were conformed to be the first-order equation,and the release of gardenoside in vitro conformed to be the zero order equation.Conclusion The matrix formulation of the DQTOG by CCD-RSD method can be used to predict the relationship between the factors and the gel transition temperature.The prepared DQTOG has good dissolution and release properties in vitro.

关 键 词：胆芩温敏眼用凝胶 泊洛沙姆407 泊洛沙姆188 丙二醇 相变温度 溶蚀性 释放性 

分 类 号：R988.1[医药卫生—药品]