应用混料设计筛选PVP K29/31直压处方

The application of mixture design to screen directly compressible PVP K29/31 formulation

目的:应用混料设计开发PVP K29/31直压处方,解决聚合物片剂处方崩解性能差的难题。方法:选择合适的处方组成包括填充剂和崩解剂,无机钾、钠盐为崩解助剂,影响片剂崩解的常用聚合物PVP K29/31等均为处方因子,崩解时间设为响应值,使用Design Expert中的混料设计设计处方。所有运行处方均采用直接压片法在相同压力条件下制备压片。制备的片剂分别进行硬度、崩解时间和脆碎度测试。通过对响应因子和数据分析建立处方预测模型,随机选择3种不同预测处方验证,确定最优处方。结果:模型显示处方中崩解剂与PVP K29/31和其他辅料有明显的交互作用,调整崩解剂的种类和比例显著影响片剂的崩解时间。结论:处方的实际崩解时间均在预测崩解时间内,可作为新药直压处方设计和优化的基础。

Objective:Mixture design is employed to design and develop directly compressible lead compact formulations with Polyyinylpyrrolidone(PVP K29/31)attempting to resolve their poor disintegrating property.Methods:Choose the right one for formulation components of fillers,disintegrating agent and typically representative polymer of PVP K29/31 were properly selected where inorganic potassium and sodium salt were also incorporated as disintegrating agents.The components and disintegration time were regarded to be formulation factors and response variable,respectively.Disintegration time is set to response value.Accordingly,formulations were generated from Mixture Design of Design Expert and prepared into compacts by direct compression at the same main forces ranges,followed by quality attributes characterization of resultant compacts including hardness,disintegration time and friability.The prediction model of immediate-disintegrating formulations was established by statistically analysing the data and corresponding factors.Three of the predicted formulations were selected at random for model validation and choose the best.Results:The developed models demonstrated that disintegrating agents significantly interacted with PVP K29/31 and the other components,which likely suggested that the disintegration time was critically affected by selectively adjusting the types and/or proportions of disintegrating agents.Conclusion:The disintegration time of predicted formulations were within the range predicted by the model,indicating that these predicted formulations were able to serve new drug formulation platform development.