Kim Hakyeong, Jang Soeun, Kim Il Won
Department of Chemical Engineering, Soongsil University, Seoul 06978, Korea.
Pharmaceutics. 2021 Apr 25;13(5):618. doi: 10.3390/pharmaceutics13050618.
Improving dissolution properties of active pharmaceutical ingredients (APIs) is a critical step in drug development with the increasing occurrence of sparingly soluble APIs. Cocrystal formation is one of the methods to alter the physicochemical properties of APIs, but its dissolution behavior in biorelevant media has been scrutinized only in recent years. We investigated the combined strategy of cocrystallization and eutectic formation in this regard and utilized the cocrystal model system of naproxen and three pyridinecarboxamide isomers. Binary melting diagrams were constructed to discover the eutectic compositions of the three cocrystals with excess amounts of pyridinecarboxamides. The melt-crystallized eutectics and cocrystals were compared in their dissolution behaviors with respect to neat naproxen. The eutectics enhanced the early dissolution rates of the cocrystals in both the absence and presence of biologically relevant bile salt and phospholipid components, whereas the cocrystal dissolution was expedited and delayed, respectively. The combined strategy in the present study will be advantageous in maximizing the utility of the pharmaceutical cocrystals.
随着难溶性活性药物成分（APIs）的出现日益增多，改善其溶出特性是药物研发中的关键步骤。共结晶形成是改变活性药物成分物理化学性质的方法之一，但近年来其在生物相关介质中的溶解行为才受到审视。在这方面，我们研究了共结晶和低共熔形成的联合策略，并利用了萘普生和三种吡啶甲酰胺异构体的共结晶模型系统。构建二元熔点图以发现三种共晶体与过量吡啶甲酰胺的低共熔组成。将熔融结晶的低共熔物和共晶体与纯萘普生的溶解行为进行了比较。在不存在和存在生物相关胆盐和磷脂成分的情况下，低共熔物均提高了共晶体的早期溶出速率，而共晶体的溶解分别加快和延迟。本研究中的联合策略将有利于最大限度地发挥药物共晶体的效用。
