通过防止形成氢键来提高难溶性药物溶解度的新见解：氨苯砜盐与樟脑磺酸和 5-磺基水杨酸的案例,CrystEngComm

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通过防止形成氢键来提高难溶性药物溶解度的新见解：氨苯砜盐与樟脑磺酸和 5-磺基水杨酸的案例
CrystEngComm ( IF 2.6 ) Pub Date : 2021-07-30 , DOI: 10.1039/d1ce00847a
Yanhui Wu ₁ , Xiujia Hao ₁ , Jianting Li ₂ , Aiying Guan ₁ , Zhengzheng Zhou ₂ , Fang Guo ₁

Affiliation

提高难溶性药物的溶解度一直是医学领域的一个具有挑战性的课题。在这方面，药物共晶策略被认为是一种有效的方法。氨苯砜（DAP）是当今治疗麻风病的一线药物，对治疗皮肤病、疟疾和其他与艾滋病有关的疾病也有效。然而，由于其水溶性低，所需的高口服剂量和相关的副作用限制了氨苯砜游离碱的耐受性和功效。在本文中，氨苯砜与磺酸的两种药物盐，即氨苯砜-樟脑磺酸（1:1）和氨苯砜-5-磺基水杨酸（1:2），分别缩写为 DAP-CAM 和 DAP-SSA，已经很容易获得并进行了调查。DAP-CAM 和 DAP-SSA 在 pH = 1.2 的缓冲溶液中显示出最高的溶解度，均高于 DAP 本身。此外，两种盐在水中的溶解度分别是 DAP 的 9.3 倍和 13.2 倍，这是迄今为止报告中改进幅度最大的。这两种 DAP 盐的溶解度提高与其结构密切相关，例如阴离子-阳离子相互作用和氢键。N-H⋯O的形成 [双键，长度为 m-dash]

DAP 分子的芳族氨基和磺酰基之间的 S 相互作用被认为不利于 DAP 加合物的溶剂化。通过引入磺酸，如樟脑磺酸和5-磺基水杨酸， [双键，长度为 m-dash]

可以防止DAP分子之间形成主要的氢键N-H⋯OS相互作用，从而提高DAP的溶解度。

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New insight into improving the solubility of poorly soluble drugs by preventing the formation of their hydrogen-bonds: a case of dapsone salts with camphorsulfonic and 5-sulfosalicylic acid

Improving the solubility of poorly soluble drugs has always been a challenging subject in the field of medicine. In this regard, a pharmaceutical cocrystal strategy has been considered to be an effective way. Dapsone (DAP) is nowadays a first-line drug for the treatment of leprosy and is also effective in the treatment of dermatoses, malaria and other AIDS-related diseases. However, because of its low aqueous solubility, the high oral doses required and associated side effects limit the tolerability and efficacy of a dapsone free base. Herein, two drug salts of dapsone with sulfonic acid, namely, dapsone–camphorsulfonic acid (1 : 1) and dapsone–5-sulfosalicylic acid (1 : 2), abbreviated as DAP–CAM and DAP–SSA respectively, have been readily obtained and investigated. DAP–CAM and DAP–SSA shows the highest solubility in the buffered solution at pH = 1.2, which are both higher than DAP itself. In addition, the solubilities of both salts are 9.3 and 13.2 times that of DAP in water, respectively, which shows the highest improvement among the reports so far. The improved solubility of these two DAP salts is closely related to their structures, such as the anion–cation interactions and hydrogen bonds. The formation of N–H⋯O [double bond, length as m-dash]

S interactions between the aromatic amino groups and sulfonyl groups of DAP molecules is considered to disfavor the solvation of the DAP adducts. By introducing sulfonic acids, such as camphorsulfonic acid and 5-sulfosalicylic acid, the formation of the main hydrogen bonding N–H⋯O [double bond, length as m-dash]

S interactions between DAP molecules can be prevented, thus enhancing the solubility of DAP.

更新日期：2021-08-16

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