Journal of Pharmaceutical Innovation ( IF 2.7 ) Pub Date : 2022-02-14 , DOI: 10.1007/s12247-022-09621-5 Sourabhkumar Jain 1 , M. M. Soniwala 1 , Nirav Kotadiya 1 , Dhavalkumar Mori 1 , Kiran Dudhat 2
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Objective
Raltegravir potassium (RP) exhibits very low water solubility over the range of physiological pH (1.2, 4.5, and 6.8), which leads to poor dissolution properties and ultimately high intra- and inter-patient variabilities. The present research work aimed to prepare RP-loaded solid self-microemulsifying drug delivery system (S-SMEDDS) of RP to improve its dissolution characteristics.
Methods
Based on results of drug solubilization capacity and emulsification efficiency, labrasol, Tween-20, and PEG-400 were selected as oil, emulsifier, and co-emulsifier, respectively. A ternary phase diagram was generated to identify the proportion of compositions that, upon mixing, formed a clear and transparent microemulsion. In the present investigation, simplex lattice design was used to explore the effect of variations in the composition of excipients on significant formulation characteristics.
Result
The regression analysis suggested a significant effect of the change in the proportion of composition on selected response variables. Optimized SMEDDS formulation was mixed with selected carriers in a mortar to prepare S-SMEDDS. The results of DSC and powder X-ray diffraction studies indicated the complete transformation of the crystalline drug into the amorphous or molecular level dispersed form when neusiline US2 was used as a carrier.
Conclusion
The results of in vitro dissolution studies proved significant improvement in the dissolution properties from the S-SMEDDS formulation compared to the pure drug (f2 < 50).
Graphical Abstract
中文翻译：
基于 DoE 的固体自微乳化给药系统 (S-SMEDDS) 方法改善拉替拉韦钾的溶出特性
客观的
拉替拉韦钾 (RP) 在生理 pH 值（1.2、4.5 和 6.8）范围内表现出非常低的水溶性，这导致溶出性能差，最终导致患者体内和患者间的高变异性。本研究旨在制备RP负载RP的固体自微乳化给药系统（S-SMEDDS），以改善其溶出特性。
方法
根据药物增溶能力和乳化效率的结果，分别选择labrasol、Tween-20和PEG-400作为油剂、乳化剂和助乳化剂。生成三元相图以确定在混合时形成澄清和透明微乳液的组合物的比例。在本研究中，单纯形点阵设计用于探索赋形剂组成变化对显着制剂特性的影响。
结果
回归分析表明组成比例的变化对选定的响应变量有显着影响。将优化的 SMEDDS 配方与选定的载体在研钵中混合以制备 S-SMEDDS。DSC和粉末X射线衍射研究结果表明，以neusiline US2为载体时，结晶药物完全转变为无定形或分子水平的分散形式。
结论
体外溶出度研究结果证明，与纯药物相比，S-SMEDDS 制剂的溶出特性显着改善 ( f 2 < 50)。
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