纳曲酮植入剂体外处方优化

In vitro optimization of naltrexone implants

目的 优化持效一个月的纳曲酮植入剂处方。方法 按照L1 6 (4 5 )正交表安排试验来考察纳曲酮植入剂的剂量、碱性添加剂用量以及控释基质聚乳酸的用量对药物体外释放的影响 ,以 1,5 ,13,2 1,30d时的累积体外药物释放百分数为指标进行多元线性回归 ,从而确立影响因素和指标间的定量关系 ,并通过重叠等高线图确定优化区域。结果 经多元线性回归获得了 3个影响因素分别与 5个不同时间点体外药物累积释放百分数之间的定量关系 ,由重叠等高线图确定了优化处方并进行了验证。结论 用重叠等高线图法完成了纳曲酮植入剂的处方优化工作 。

OBJECTIVE To develop and optimize the formulation of naltrexone implants (NTX IMPs) which would be effective over one month period.METHODS An L 16 (4 5) orthogonal design was used to investigat the effects of three formulation variables [the dosage of implants,the content of basic additive,Mg(OH) 2,and the content of poly lactic acid on in vitro drug release profiles.The in vitro release percentages in 1,5,13,21 and 30 days were determined as the response parameters.The correlations between variables and response parameters were calculated by multiple linear regression,and the optimal region for the implant formulation was identified in a superimposed contour plot.RESULTS The quantitative relationships between three formulation variables and in vitro release percentages in 1,5,13,21 and 30 days were obtained.The optimized NTX IMPs which have the desired in vitro drug release characteristics were obtained from the superimposed contour plot.CONCLUSION The desired NTX implants were developed by means of a superimposed contour plot.Such method can be used in optimizing of multiple response parameters.