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

共结晶是一种在不改变化学结构的情况下改善活性药物成分固体性质的制药技术。本研究以扑热息痛(对乙酰氨基酚)为模型药物，从分子水平上阐明共晶形成机理。通过机械力化学反应在固相中的探索性筛选研究，发现了三种新的共晶。特别是，扑热息痛和三甲基甘氨酸(甜菜碱)以1：1的摩尔比组成的药物共晶体显示出更好的药物性能，如致密的成型性和溶解行为。此外，还制备了纳克尺度的共晶，并用显微拉曼光谱对其进行了评价。

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.