Telmisartan is an anti-hypertensive drug that exhibits poor aqueous solubility. In this work, salt formation was utilized to address this issue. Three hydrochloride salts of telmisartan (TELHCl), a trihemihydrate hydrochloride salt (TELHCl-Hyd), and two anhydrate forms (TELHCl-A and TELHCl-B) were obtained. The crystal structures of TELHCl-Hyd and TELHCl-A were determined using single-crystal structure analysis. TELHCl-Hyd is a channel hydrate that has structural similarities with TELHCl-A. The structures of both crystals are mainly composed of chain structures formed by centrosymmetric dimers connected via carboxylic–benzimidazole hydrogen bonding. Despite their structural similarities, the dehydration of TELHCl-Hyd led to the formation of TELHCl-B. The solubility, intrinsic dissolution rate (IDR), powder flowability, and tabletability of TELHCl-Hyd and TELHCl-B were characterized and compared with those of the telmisartan free base form (TEL). The hydrochloride salts enhanced the solubility of telmisartan approximately 10 to 20 times and maintained the spring parachute effect up to 24 h. The IDR was also improved due to the existence of a hydrophilic channel that facilitates the dissolution of telmisartan cations. The resulting salts had a larger particle size and a more favorable crystal morphology that led to a better powder flowability. However, the tabletability was not improved by salt formation. The TEL exhibited a defined slip plane and a higher specific surface area that may assist the tableting process.

中文翻译：

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盐酸替米沙坦盐的结构表征及药学评价

替米沙坦是一种水溶性较差的抗高血压药物。在这项工作中，利用盐的形成来解决这个问题。获得替米沙坦的三种盐酸盐(TELHCl)、三半水合物盐酸盐(TELHCl-Hyd)和两种无水物形式(TELHCl-A和TELHCl-B)。使用单晶结构分析确定了 TELHCl-Hyd 和 TELHCl-A 的晶体结构。 TELHCl-Hyd 是一种通道水合物，与 TELHCl-A 结构相似。两种晶体的结构主要由中心对称二聚体通过羧基-苯并咪唑氢键连接形成的链结构组成。尽管它们的结构相似，但 TELHCl-Hyd 脱水导致形成 TELHCl-B。对 TELHCl-Hyd 和 TELHCl-B 的溶解度、固有溶出速率 (IDR)、粉末流动性和可压片性进行了表征，并与替米沙坦游离碱形式 (TEL) 进行了比较。盐酸盐使替米沙坦的溶解度提高约10至20倍，并将弹簧降落伞效应维持长达24小时。由于存在促进替米沙坦阳离子溶解的亲水通道，IDR 也得到改善。所得盐具有更大的粒径和更有利的晶体形态，从而导致更好的粉末流动性。然而，成盐并没有改善可压片性。 TEL 具有明确的滑移面和较高的比表面积，有助于压片过程。