Salem Ala', Hagymási Alexandra, Vörös-Horváth Barbara, Šafarik Tatjana, Balić Tomislav, Szabó Péter, Gősi Fruzsina, Nagy Sándor, Pál Szilárd, Kunsági-Máté Sándor, Széchenyi Aleksandar
Institute of Pharmaceutical Technology and Biopharmacy, University of Pécs, Pécs, Hungary.
Department of Chemistry, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
Eur J Pharm Sci. 2021 Jan 1;156:105599. doi: 10.1016/j.ejps.2020.105599. Epub 2020 Oct 16.
Despite polymorphism of crystalline active pharmaceutical ingredients (APIs) being a common phenomenon, reports on polymorphic co-crystals are limited. As polymorphism can vastly affect API properties, controlling polymorph generation is crucial. Control of the polymorph nucleation through the use of different solvents during solution crystallization has been used to obtain a desirable crystal polymorph. There have been two reported polymorphic forms of the 4-aminosalicylic acid-sulfamethazine co-crystals. These forms were found to have different thermodynamic stabilities. However, the control of co-crystal polymorph generation using preparation parameter manipulation has never been reported. The aim of this study was to establish the effect of different solvent parameters on the formation of different co-crystal polymorphic forms. Selection of the solvents was based on Hansen Solubility Parameters (HSPs) as solvents with different solubility parameters are likely to interact differently with APIs, ultimately affecting co-crystallization. Eight solvents with different HSPs were used to prepare co-crystals by solvent evaporation at two different temperatures. Through characterization of the co-crystals, a new polymorph has been obtained. The hydrogen bond acceptability seemed to affect the co-crystal form obtained more than the hydrogen bond donation ability. Furthermore, the use of HSPs can be utilized as an easy calculation method in screening and design of co-crystals.
尽管结晶活性药物成分（API）的多晶型现象很常见，但关于多晶型共晶体的报道却很有限。由于多晶型会极大地影响API的性质，控制多晶型的产生至关重要。在溶液结晶过程中通过使用不同的溶剂来控制多晶型成核已被用于获得理想的晶体多晶型。已报道4-氨基水杨酸-磺胺二甲嘧啶共晶体有两种多晶型形式。发现这些形式具有不同的热力学稳定性。然而，从未有过关于通过制备参数操纵来控制共晶体多晶型产生的报道。本研究的目的是确定不同溶剂参数对不同共晶体多晶型形式形成的影响。溶剂的选择基于 Hansen 溶解度参数（HSP），因为具有不同溶解度参数的溶剂可能与API有不同的相互作用，最终影响共结晶。使用八种具有不同HSP的溶剂在两个不同温度下通过溶剂蒸发制备共晶体。通过对共晶体的表征，获得了一种新的多晶型。氢键接受能力似乎比氢键供体能力对所获得的共晶体形式影响更大。此外，HSP的使用可作为共晶体筛选和设计中的一种简便计算方法。
