奥拉西坦的逐步冻凝结晶

Progressively frozen condensation crystallization of oxiracetam

奥拉西坦简单冻干往往导致所需时间长、产品质量差等问题,本文应用MS软件计算了山梨醇和奥拉西坦晶体各个晶面的相互作用能,结果表明山梨醇和奥拉西坦之间的相互作用能较小,实验也证明冻干过程中奥拉西坦晶型、晶习不受山梨醇影响。通过DSC和热台显微镜分析,奥拉西坦简单冻干问题的关键因素在于原预冻过程处方逐步冻凝产生的是玻璃态,不利于水分子升华干燥,因此本文提出奥拉西坦冻干过程的逐步冻凝结晶工艺,改变山梨醇的结晶状态,使各组分分别冻凝分离成微晶态,实验放大结果表明冻干所需时间大幅度缩短,产品质量得到很大提高。

It is found that direct freeze-drying method is not applicable to oxiracetam because of long time and poor product quality. In this paper, MS software is used to calculate the molecular interactions between additive （sorbitol） and different crystal surfaces of oxiracetam. These values are very small and could be neglected. Experiments also show that the crystal form and morphology are independent of sorbitol in freeze-drying process. Analyzed by differential scanning calorimetry and hot-stage microscopy, glassy sate of oxiracetam prescription is identified during original prefreezing process, against sublimation of water molecules. Therefore, we propose a gradual congelation crystallization technology to change the crystal state of sorbitol, congeal every component and separate them in microcrystalline. According to results of larger scale experiments, this new technique greatly shortens the time required and improves the product quality.