Drug-Drug Multicomponent Solid Forms: Cocrystal, Coamorphous and Eutectic of Three Poorly Soluble Antihypertensive Drugs Using Mechanochemical Approach
Drug-Drug Multicomponent Solid Forms: Cocrystal, Coamorphous and Eutectic of Three Poorly Soluble Antihypertensive Drugs Using Mechanochemical Approach
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DOI：
10.1208/s12249-016-0701-1
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发表时间：
2017-08-01
影响因子：
3.3
通讯作者：
Chadha, Renu
中科院分区：
文献类型：
--
作者：
Haneef, Jamshed;Chadha, Renu
本研究采用机械化学方法，以阿替洛尔为共成形剂，制备了三种难溶性抗高血压药物（替米沙坦、厄贝沙坦和氢氯噻嗪）的药物-药物多组分固体制剂。所得固体形式包括共晶（替米沙坦-阿替洛尔）、共晶（厄贝沙坦-阿替洛尔）和共晶（氢氯噻嗪-阿替洛尔）。该研究强调，药物分子固态转化为新形式是结构模式改变、二聚体减少和基于结构相似性产生新的易氢键网络的结果。两种不同药物之间的异聚或同聚相互作用的倾向导致了不同的固体形式（共晶/共晶/共晶），并成为这项研究工作的一个有趣的方面。对这些固体形式的评价揭示了溶解度和溶出度的增加，导致在醋酸脱氧皮质酮（DOCA）盐诱导的动物模型中具有更好的抗高血压活性。因此，这些药物-药物多组分固体形式的开发是解决溶解度差的问题的有前景和可行的方法，并且在用于治疗高血压的双重药物疗法中可能具有相当大的兴趣。
The present study deals with the application of mechanochemical approach for the preparation of drug-drug multicomponent solid forms of three poorly soluble antihypertensive drugs (telmisartan, irbesartan and hydrochlorothiazide) using atenolol as a coformer. The resultant solid forms comprise of cocrystal (telmisartan-atenolol), coamorphous (irbesartan-atenolol) and eutectic (hydrochlorothiazide-atenolol). The study emphasizes that solid-state transformation of drug molecules into new forms is a result of the change in structural patterns, diminishing of dimers and creating new facile hydrogen bonding network based on structural resemblance. The propensity for heteromeric or homomeric interaction between two different drugs resulted into diverse solid forms (cocrystal/coamorphous/eutectics) and become one of the interesting aspects of this research work. Evaluation of these solid forms revealed an increase in solubility and dissolution leading to better antihypertensive activity in deoxycorticosterone acetate (DOCA) salt-induced animal model. Thus, development of these drug-drug multicomponent solid forms is a promising and viable approach to addressing the issue of poor solubility and could be of considerable interest in dual drug therapy for the treatment of hypertension.