Purpose

Clofazimine displays high intersubject variability in absorption after oral administration because of its extremely low water solubility and high lipophilicity. The present investigation was aimed to prepare self micro emulsifying drug delivery system (SMEDDS) of clofazimine for improving its dissolution properties by using design of experiment (DoE) approach.

Methods

Various lipid, surfactant, and co-surfactants were screened based on their ability to solubilize clofazimine and their ability to make a clear transparent microemulsion upon dilution with water. Based on these tests, Capmul MCM, Tween-20, and Labrasol were selected as lipid, surfactant, and co-surfactant respectively. The design batches were prepared according to simplex lattice design and the optimized batch was selected by using the desirability function of design expert software. Contour plots and response surface plots were generated to understand the effect changed in formulation composition on critical product parameters (globule size and cumulative percentage drug release in 30 min).

Results

All the prepared batches released more than 85% drug in less than 60 min in 1.2 pH HCl and 6.8 Phosphate buffer. The validity of the model was proved by observed close agreement between the experimentally obtained values for optimized batch and predicted values given by the polynomial equation.

Conclusion

The present investigation successfully demonstrated the effectiveness of the simplex lattice design and desirability function for optimizing the SMEDDS formulation and its ability to explain the effects of formulation variables on critical product attributes.

中文翻译：

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简单晶格设计和期望函数在克洛他明SMEDDS的制定和优化中的应用

目的

氯吡嗪明的水溶性极低，亲脂性很高，口服后在受试者之间显示出较高的受试者间吸收变异性。本研究旨在通过实验设计（DoE）方法制备氯吡嗪胺的自微乳化药物递送系统（SMEDDS），以改善其溶出特性。

方法

根据溶解氯吡嗪的能力和用水稀释后制备透明透明微乳液的能力，筛选各种脂质，表面活性剂和辅助表面活性剂。根据这些测试，分别选择Capmul MCM，Tween-20和Labrasol作为脂质，表面活性剂和辅助表面活性剂。根据单纯形晶格设计准备设计批次，并使用设计专家软件的期望功能选择优化的批次。生成等高线图和响应面图以了解制剂组成对关键产品参数（球大小和30分钟内药物累积释放百分比）的影响。

结果

所有制备的批次均在不到60分钟的时间内在1.2 pH HCl和6.8磷酸盐缓冲液中释放了超过85％的药物。通过观察到的最佳批次的实验获得的值与多项式方程式给出的预测值之间的密切一致性，证明了该模型的有效性。

结论

本研究成功地证明了用于优化SMEDDS配方的单纯形晶格设计和合意性功能的有效性及其解释配方变量对关键产品属性的影响的能力。