Purpose

The development of pH-independent drugs is difficult because it involves improvements in their solubility and dissolution (%) in solubilizer. In the present study, the pH-independent cilostazol (CLT) was formulated for enhanced solubility and dissolution (%) and for maintaining stability with meglumine by the solid dispersion (SD) technique.

Methods

The CLT formulations were prepared with weak acid or weak base by solvent evaporation method. Moreover, the physical properties of the optimal SD formulation that were evaluated were thermal property, crystallinity, and drug-excipient interaction.

Results

Based on the pre-dissolution test, meglumine and Aerosil®200 were selected as the weak base and carrier, respectively. The SD1 formulation (CLT:meglumine:Aerosil®200 at 1:1:0.5, w/w) enhanced the dissolution (%) of CLT in distilled water/pH 1.2/pH 6.8 buffer by 1.20-/1.13-/1.18-fold, respectively, compared with those of Pletal®. Moreover, SD1 formulation was stable at room temperature for 3 months. A slight change in the crystallinity of CLT was observed in the SD1 formulation, which may be due to intermolecular interaction between CLT and meglumine.

Conclusions

The SD1 formulation showed improved dissolution (%) and might improve the bioavailability and efficacy of CLT.

中文翻译：

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西洛他唑增溶和稳定使用无聚合物固体分散体系

目的

不依赖pH值的药物的开发非常困难，因为它需要改善其在增溶剂中的溶解度和溶解度（％）。在本研究中，通过固体分散体（SD）技术配制了不依赖pH值的西洛他唑（CLT），以提高溶解度和溶解度（％），并保持葡甲胺的稳定性。

方法

通过溶剂蒸发法用弱酸或弱碱制备了CLT制剂。此外，评估的最佳SD制剂的物理性质是热性质，结晶度和药物-赋形剂相互作用。

结果

根据溶解前测试，分别选择葡甲胺和200作为弱碱和载体。SD1配方（CLT：meglumine：Aerosil®2001：1：0.5，w / w）将CLT在蒸馏水/ pH 1.2 / pH 6.8缓冲液中的溶解度（％）提高了1.20- / 1.13- / 1.18倍分别与Pletal®比较。而且，SD1制剂在室温下稳定3个月。在SD1配方中观察到CLT结晶度的轻微变化，这可能是由于CLT和葡甲胺之间的分子间相互作用所致。

结论

SD1制剂显示出改善的溶出度（％），可能会改善CLT的生物利用度和功效。