Preparation and formulation of pharmaceutical nano-cocrystals by using mechanochemical reaction

共结晶是一种在不改变活性药物成分化学结构的情况下改善其固体性质的制药技术。本研究以扑热息痛（扑热息痛）为模型原料药，在分子水平上阐明共晶的形成机制。利用机械化学反应在固体条件下进行筛选研究，发现了三种新型共晶。特别是，由对乙酰氨基酚和三甲基甘氨酸（甜菜碱）组成的摩尔比为1:1的药物共晶表明，药物性能得到改善，如致密的可塑性和溶解性。此外，还实现了纳米级共晶的制备和显微拉曼光谱评价。

Cocrystallization is a pharmaceutical technology which provides an improvement on solid properties of active pharmaceutical ingredients without modification of its chemical structure. In this study, paracetamol (acetaminophen) was used as model drug substance and to clarify the formation mechanism of cocrystal in molecular level. As a result of exploring screening study in solid state using mechanochemical reaction, novel three cocrystals were discovered. In particular, the pharmaceutical cocrystal consisting of paracetamol and trimethylglycine (betaine) at molar ration of 1:1 indicated improved pharmaceutical properties such as compact moldability and dissolution behavior. In addition, preparing cocrystal in nanogram scale and evaluating by using microscopic Raman spectroscopy were achieved.