Purpose

Evaluating the feasibility of two-step preparation of clotrimazole solid glass solutions for improving its physicochemical properties, intrinsic dissolution, and antifungal activity.

Methods

Co-grinding with selected coformers including vitamin C and L-arginine was employed to form co-amorphous dispersions; then, a polymeric carrier was added to form a homogenous glass solution. The solid solutions were converted to nanosuspensions after reconstitution and ultrasonication. The dispersions were characterized for equilibrium solubility, intrinsic dissolution, particle size, and zeta potential. Solid state characterization was carried out using differential scanning calorimetry, X-ray powder diffraction, and Infrared spectroscopy. The antifungal activity was evaluated using candida albicans species.

Results

Equilibrium solubility indicated superb increase in clotrimazole solubility (more than 289 times) from glass solutions compared to pure crystalline drug. The intrinsic dissolution data showed 64% ± 0.34 of drug released within 15 min, and complete dissolution was obtained in 45 min. The ideal formula showed nanosized particles after dispersion in water (225 nm), optimum zeta potential (20.20 µV), and polydispersity index (0.35). Solid state characterization showed shortened peaks and diffraction lines of the glass solutions compared to parent components. The biological activity of the reconstituted nanosuspension showed decreased minimum inhibitory concentration by 50% and increased area of growth inhibition zones of candida albicans by more than 28% compared to drug solution.

Conclusions

These findings suggest that solid glass solutions and its derived nanosuspensions of clotrimazole with ascorbic acid and polyvinyl pyrrolidone could be a valuable solution for maximizing drug bioavailability.

中文翻译：

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克霉唑固体玻璃溶液的制备和转化为具有改善物理化学和抗真菌性能的纳米混悬剂

目的

评估两步法制备克霉唑固体玻璃溶液以改善其理化性质、固有溶解度和抗真菌活性的可行性。

方法

与包括维生素 C 和 L-精氨酸在内的选定共形成物共同研磨以形成共无定形分散体；然后，添加聚合物载体以形成均匀的玻璃溶液。在重构和超声处理后，固溶体转化为纳米悬浮液。分散体的特征在于平衡溶解度、固有溶解度、粒度和 zeta 电位。使用差示扫描量热法、X射线粉末衍射和红外光谱进行固态表征。使用白色念珠菌物种评估抗真菌活性。

结果

平衡溶解度表明，与纯结晶药物相比，玻璃溶液的克霉唑溶解度显着增加（超过 289 倍）。固有溶出度数据显示，64%±0.34 的药物在 15 分钟内释放，在 45 分钟内获得完全溶出。理想的配方显示纳米级颗粒分散在水中后 (225 nm)、最佳 zeta 电位 (20.20 µV) 和多分散指数 (0.35)。固态表征显示，与母体组分相比，玻璃溶液的峰和衍射线缩短。与药物溶液相比，重组纳米混悬剂的生物活性显示，最小抑制浓度降低了 50%，白色念珠菌的生长抑制区面积增加了 28% 以上。

结论

这些发现表明，固体玻璃溶液及其衍生的克霉唑与抗坏血酸和聚乙烯吡咯烷酮的纳米混悬剂可能是最大化药物生物利用度的有价值的解决方案。