Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; R&D Drug Product Development, Hovione Farmaciência SA, Loures, Portugal.
R&D Drug Product Development, Hovione Farmaciência SA, Loures, Portugal.
Int J Pharm. 2016 Jun 15;506(1-2):68-78. doi: 10.1016/j.ijpharm.2016.04.010. Epub 2016 Apr 9.
Pharmaceutical cocrystals are used as a strategy to overcome poor physicochemical properties of drugs. The use of cocrystals in the pharmaceutical industry remains to be fully exploited due, in part, to the scarcity of suitable large-scale production methods and lack of robust and cost-effective processes. To overcome these challenges, spray congealing was used for the first time in the preparation of cocrystals. The work considered a feasibility study, followed by a design of experiments to assess the impact of varying atomization and cooling-related process parameters on cocrystal formation, purity, particle size, shape and bulk powder flow properties. It was demonstrated that spray congealing could be used to produce cocrystals. The thermal analysis and X-ray results of the spray-congealed products were different from the pure components or physical mixtures and were aligned with those reported for the same cocrystals systems produced by other techniques. Cocrystal particles were compact and spherical consisting of aggregates of individual cocrystals entangled or adhered with each other. From the design of experiments, the results demonstrated that varying the process parameters did not influence cocrystal formation, but had an impact on cocrystal purity. Moreover, it was demonstrated that cocrystal particle properties can be adjusted, in situ, by varying atomization and cooling efficiency, in order to produce particles more suited for incorporation in final dosage forms such as tablets.
药物共晶被用作克服药物物理化学性质差的策略。由于缺乏合适的大规模生产方法和缺乏强大且具有成本效益的工艺，药物共晶在制药行业的应用仍有待充分开发。为了克服这些挑战，喷雾凝固法首次用于共晶的制备。这项工作首先进行了可行性研究，然后进行了实验设计，以评估雾化和冷却相关过程参数的变化对共晶形成、纯度、粒径、形状和散装粉末流动性能的影响。结果表明，喷雾凝固法可用于生产共晶。喷雾凝固产物的热分析和 X 射线结果与纯组分或物理混合物不同，与其他技术生产的相同共晶系统的报告结果一致。共晶颗粒紧密且呈球形，由单个共晶的聚集体组成，这些聚集体相互缠绕或粘附在一起。从实验设计的结果可以看出，改变工艺参数不会影响共晶的形成，但会影响共晶的纯度。此外，还证明可以通过改变雾化和冷却效率来原位调整共晶颗粒的性质，以便生产出更适合于最终剂型（如片剂）的颗粒。
