Purpose

The primary objective of this research work was to formulate crystal engineered multicomponent form of a BCS II drug, telmisartan (TEL) using crystal engineering approach to improve its aqueous solubility. Further, it was attempted to understand the co-crystallization specificity of TEL using a set of structurally similar coformers.

Methods

Preliminary structural assessment and feasibility of cocrystal formation was done using Cambridge structural database (CSD) and molecular electrostatic surface potential (MESP). The formation of cocrystals was confirmed by different characterization techniques such as differential scanning calorimetry (DSC), hot stage microscopy (HSM), Fourier transform infrared spectroscopy (FTIR), and powder x-ray diffraction (PXRD). Solubility and dissolution studies were performed in phosphate buffer 7.5 and 0.1 N HCl.

Results

TEL cocrystal with maleic acid (MA) was successfully obtained, and co-crystallization specificity was decoded at MESP. Cocrystal structure was also solved from PXRD data. A 4.27-fold and 2.8-fold improvement in the solubility was observed in phosphate buffer 7.5 and 0.1 N HCl.

Conclusion

A significant improvement in the aqueous solubility and dissolution profile was observed for the prepared cocrystals over the pure TEL. The present study was a small initiative to serve as a guidance for the rationalized screening and preparation of novel multicomponent solids with desired properties.

中文翻译：

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相似但不相同：结构相似的共聚体对替米沙坦共结晶的影响

目的

这项研究工作的主要目标是使用晶体工程方法配制 BCS II 药物替米沙坦 (TEL) 的晶体工程多组分形式，以提高其水溶性。此外，尝试使用一组结构相似的共形成物来了解 TEL 的共结晶特异性。

方法

使用剑桥结构数据库（CSD）和分子静电表面电势（MESP）进行了初步结构评估和共晶形成的可行性。通过不同的表征技术，如差示扫描量热法 (DSC)、热台显微镜 (HSM)、傅里叶变换红外光谱 (FTIR) 和粉末 X 射线衍射 (PXRD) 证实了共晶的形成。溶解度和溶出度研究在磷酸盐缓冲液 7.5 和 0.1 N HCl 中进行。

结果

成功获得了TEL与马来酸（MA）的共晶，并在MESP上解码了共晶的特异性。共晶结构也可以从 PXRD 数据中解析出来。在磷酸盐缓冲液 7.5 和 0.1 N HCl 中观察到溶解度分别提高了 4.27 倍和 2.8 倍。

结论

与纯 TEL 相比，制备的共晶的水溶性和溶解曲线显着改善。本研究是一项小型举措，旨在为合理筛选和制备具有所需性能的新型多组分固体提供指导。