Pharmaceutical co-crystals of the anti-inflammatory drug diflunisal and nicotinamide obtained using supercritical CO2 as an antisolvent
Pharmaceutical co-crystals of the anti-inflammatory drug diflunisal and nicotinamide obtained using supercritical CO2 as an antisolvent
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DOI：
10.1016/j.jcou.2015.11.006
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发表时间：
2016-03-01
影响因子：
7.7
通讯作者：
Pando, Concepcion
中科院分区：
文献类型：
--
作者：
Cuadra, Isaac A.;Cabanas, Albertina;Pando, Concepcion
探索了基于使用超临界CO2作为抗溶剂的方法（SAS方法）作为共结晶技术。共结晶是一种新兴的和强大的技术，以改善活性药物成分的物理化学性质。通常采用的固态和溶液共结晶方法存在几个缺点。一步SAS方法对环境的影响很小，并克服了与传统方法相关的一些困难。本文首次用SAS法制备了抗炎药二氟尼柳（DIF）和烟酰胺（NIC）的2：1共晶。使用对应于共晶化学计量组成的药物浓度。研究了SAS参数温度（35和40 ℃）、压力（10.0和12.0 MPa）、药物浓度（两个水平）和溶剂（丙酮和乙醇）对共晶形成的影响。获得具有均匀宽度和更可变长度的针状晶体材料。出于比较的目的，纯DIF和NIC也由SAS处理。共晶体的特征在于结晶度、热行为、共形成物相互作用和药物释放;它们的溶出速率相对于纯DIF的溶出速率提高。SAS共晶表现出与先前通过液体辅助球磨研磨和溶液结晶获得的那些相同的晶体结构、熔点和FTIR光谱。(C)2015爱思唯尔有限公司版权所有。
A method based on using supercritical CO2 as an antisolvent (SAS method) is explored as a co-crystallization technique. Co-crystallization is an emerging and powerful technique to improve the physicochemical properties of an active pharmaceutical ingredient. The solid-state and solution co-crystallization methods usually employed present several disadvantages. The one-step SAS method has a low environmental impact and overcomes some of the difficulties associated to conventional methods. The 2: 1 co-crystals of the anti-inflammatory drug diflunisal (DIF) and nicotinamide (NIC) are prepared for the first time by SAS. Drug concentrations corresponding to the co-crystal stoichiometric composition are used. The influence of the SAS parameters temperature (35 and 40 degrees C), pressure (10.0 and 12.0 MPa), drug concentration (two levels) and solvent (acetone and ethanol) in the co-crystal formation is studied. A crystalline material in the form of needles of uniform width and more variable length is obtained. For comparison purposes, pure DIF and NIC are also processed by SAS. Co-crystals are characterized in terms of crystallinity, thermal behavior, coformer interactions and drug release; their dissolution rate improves with respect to that of pure DIF. SAS co-crystals exhibit the same crystal structure, melting point and FTIR spectrum as those previously obtained by liquid assisted ball mill grinding and solution crystallization. (C) 2015 Elsevier Ltd. All rights reserved.