当前位置：
X-MOL 学术
›
Mol. Pharmaceutics
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Insights into Dissolution and Solution Chemistry of Multidrug Formulations of Antihypertensive Drugs.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-09-01 , DOI: 10.1021/acs.molpharmaceut.0c00835 Mira El Sayed 1, 2 , Amjad Alhalaweh 2 , Christel A S Bergström 1
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-09-01 , DOI: 10.1021/acs.molpharmaceut.0c00835 Mira El Sayed 1, 2 , Amjad Alhalaweh 2 , Christel A S Bergström 1
Affiliation
|
Using fixed dose combinations of drugs instead of administering drugs separately can be beneficial for both patients and the health care system, but the current understanding of how multidrug formulations work at the molecular level is still in its infancy. Here, we explore dissolution, solubility, and supersaturation of various drug combinations in amorphous formulations. The effect of chemical structural similarity on combination behavior was investigated by using structurally related compounds of both drugs. The effect of polymer type on solution behavior was also evaluated using chemically diverse polymers. Indapamide (IPM) concentration decreased when combined with felodipine (FDN) or its analogues, which occurred even when the IPM solution was undersaturated. The extent of solubility decrease of FDN was less than that of IPM from the dissolution of an equimolar formulation of the drugs. No significant solubility decrease was observed for FDN at low contents of IPM which was also observed for other dihydropyridines, whereas FDN decreases at high contents of IPM. This was explained by the complex nature of the colloidal precipitates of the combinations which impacts the chemical potential of the drugs in solution at different levels. The maximum achievable concentration of FDN and IPM during dissolution of the polyvinylpyrrolidone-based amorphous solid dispersion was higher than the value measured with the hydroxypropyl methylcellulose acetate succinate-based formulation. This emphasizes the significance of molecular properties and chemical diversity of drugs and polymers on solution chemistry and solubility profiles. These findings may apply to drugs administered as a single dosage form or in separate dosage forms and hence need to be well controlled to assure effective treatments and patient safety.
中文翻译：
深入了解抗高血压药物多药制剂的溶出度和溶液化学。
使用固定剂量的药物组合而不是单独给药对患者和医疗保健系统都有益，但目前对多药制剂如何在分子水平上发挥作用的理解仍处于起步阶段。在这里，我们探讨了无定形制剂中各种药物组合的溶出度、溶解度和过饱和度。通过使用两种药物的结构相关化合物研究化学结构相似性对组合行为的影响。聚合物类型对溶液行为的影响也使用化学性质不同的聚合物进行了评估。当与非洛地平 (FDN) 或其类似物联合使用时，吲达帕胺 (IPM) 浓度会降低，即使 IPM 溶液不饱和也会发生这种情况。由于药物等摩尔制剂的溶解，FDN 溶解度降低的程度小于 IPM。FDN 在低 IPM 含量下没有观察到显着的溶解度降低，这在其他二氢吡啶中也观察到，而 FDN 在 IPM 含量高时降低。这是通过组合胶体沉淀的复杂性质来解释的，它影响药物在不同水平的溶液中的化学势。在基于聚乙烯吡咯烷酮的无定形固体分散体溶解过程中 FDN 和 IPM 的最大可达到浓度高于使用基于乙酸琥珀酸羟丙基甲基纤维素的制剂测得的值。这强调了药物和聚合物的分子特性和化学多样性对溶液化学和溶解度曲线的重要性。这些发现可能适用于作为单一剂型或单独剂型给药的药物，因此需要很好地控制以确保有效治疗和患者安全。
更新日期：2020-10-05
中文翻译：
深入了解抗高血压药物多药制剂的溶出度和溶液化学。
使用固定剂量的药物组合而不是单独给药对患者和医疗保健系统都有益，但目前对多药制剂如何在分子水平上发挥作用的理解仍处于起步阶段。在这里，我们探讨了无定形制剂中各种药物组合的溶出度、溶解度和过饱和度。通过使用两种药物的结构相关化合物研究化学结构相似性对组合行为的影响。聚合物类型对溶液行为的影响也使用化学性质不同的聚合物进行了评估。当与非洛地平 (FDN) 或其类似物联合使用时，吲达帕胺 (IPM) 浓度会降低，即使 IPM 溶液不饱和也会发生这种情况。由于药物等摩尔制剂的溶解，FDN 溶解度降低的程度小于 IPM。FDN 在低 IPM 含量下没有观察到显着的溶解度降低，这在其他二氢吡啶中也观察到，而 FDN 在 IPM 含量高时降低。这是通过组合胶体沉淀的复杂性质来解释的，它影响药物在不同水平的溶液中的化学势。在基于聚乙烯吡咯烷酮的无定形固体分散体溶解过程中 FDN 和 IPM 的最大可达到浓度高于使用基于乙酸琥珀酸羟丙基甲基纤维素的制剂测得的值。这强调了药物和聚合物的分子特性和化学多样性对溶液化学和溶解度曲线的重要性。这些发现可能适用于作为单一剂型或单独剂型给药的药物，因此需要很好地控制以确保有效治疗和患者安全。
京公网安备 11010802027423号