Purpose

Glimepiride, an anti-diabetic and third-generation sulfonylurea drug belonging to class II BCS (Biopharmaceutical Classification System) type, is characterized by its low solubility and high permeability. In order to increase glimepiride’s aqueous solubility and hence increase its dissolution rate, the goal of this study was to formulate the drug as binary and ternary solid dispersion employing water-soluble carriers.

Methods

Three binary solid dispersions of glimepiride were prepared by solvent evaporation technique using β-cyclodextrin with different drug carrier ratios. After optimizing the binary solid dispersion concerning solubility improvement, four different ratios of ternary solid dispersion employing polyvinylpyrrolidone K30 (PVPK30) were fabricated with the optimized solid dispersion to determine solubility and compared with marketed formulation to determine the consequence of the study. Further FTIR, XRD, and DSC studies were performed for a better understanding of the characterization of optimized solid dispersion and to know if there are any significant interactions with water-soluble carriers or with excipients.

Results

The combination of the glimepiride and β-cyclodextrin systems significantly increases the solubility and in the case of ternary solid dispersion, the solubility is increased even more. The enhancement of the solubility is influenced by the carrier’s concentration.

Conclusions

A total of four tablet formulation batches that were prepared and the explicit in vitro comparisons been carried out with commercially available immediate-release formulation, suggested that formulating glimepiride in ternary solid dispersion has enhanced the solubility and dissolution rate drastically.

Graphical Abstract

中文翻译：

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二元和三元固体分散技术在提高格列美脲溶解度和溶出度方面的潜在突破以及与市售制剂的体外比较

目的

格列美脲是一种抗糖尿病的第三代磺酰脲类药物，属于BCS（生物制药分类系统）II类药物，具有低溶解度、高渗透性的特点。为了增加格列美脲的水溶性，从而提高其溶出速率，本研究的目标是将药物配制成采用水溶性载体的二元和三元固体分散体。

方法

以不同载药比例的β-环糊精为原料，采用溶剂蒸发法制备了三种格列美脲二元固体分散体。在优化二元固体分散体以提高溶解度后，使用优化的固体分散体制备了四种不同比例的聚乙烯吡咯烷酮K30（PVPK30）三元固体分散体，以确定溶解度，并与市售制剂进行比较，以确定研究结果。为了更好地了解优化固体分散体的表征，并了解是否与水溶性载体或赋形剂存在任何显着的相互作用，进行了进一步的 FTIR、XRD 和 DSC 研究。

结果

格列美脲和β-环糊精体系的组合显着增加了溶解度，并且在三元固体分散体的情况下，溶解度增加得更多。溶解度的增强受载体浓度的影响。

结论

总共制备了四个批次的片剂制剂，并与市售速释制剂进行了明确的体外比较，表明将格列美脲配制为三元固体分散体大大提高了溶解度和溶出速率。

图形概要