Cysewski Piotr
Department of Physical Chemistry, Pharmacy Faculty, Collegium Medicum of Bydgoszcz, Nicolaus Copernicus University in Toruń, Kurpińskiego 5, 85-096, Bydgoszcz, Poland.
J Mol Model. 2018 Apr 21;24(5):112. doi: 10.1007/s00894-018-3649-0.
The solubility advantage (SA) of meloxicam cocrystalized with mono- and dicarboxylic acids was expressed in terms of equilibrium constants involving active pharmaceutical ingredient and coformer in aqueous solutions. It is argued that SA can be quantified by concentration of pairs formed in water. The pH and concentration of dissolved components is included explicitly in the model. The alternative behavior of mono- and dicarboxylic acids was emphasized and addressed to different structural motifs. The structural and energetic properties of meloxicam and its complexes with carboxylic acids were characterized, including tautmerism and dissociation in aqueous media. In particular, performed in silico modeling confirmed experimental observation that meloxicam dissolved in water or modest acidic solutions is expected to be a mixture of anionic form in equilibrium with at least five neutral isomers. Tautomer-related diversity of pairs formation and the possibility of salt formation is also discussed. Graphical abstract Two types of motifs found in meloxicam cocrystals reveal two sources of solubility advantage.
美洛昔康与一元和二元羧酸共结晶的溶解度优势（SA）通过涉及活性药物成分和共形成剂在水溶液中的平衡常数来表示。有人认为，SA可以通过水中形成的配对物浓度来量化。该模型明确包含了溶解成分的pH值和浓度。强调了一元和二元羧酸的不同行为，并针对不同的结构 motif 进行了探讨。对美洛昔康及其与羧酸复合物的结构和能量性质进行了表征，包括在水性介质中的互变异构和离解。特别是，计算机模拟证实了实验观察结果，即溶解在水或适度酸性溶液中的美洛昔康预计是阴离子形式与至少五种中性异构体处于平衡的混合物。还讨论了与互变异构相关的配对物形成多样性以及形成盐的可能性。图形摘要 在美洛昔康共晶体中发现的两种类型的 motif 揭示了溶解度优势的两个来源。
