This study uses a cooling sonocrystallization process to recrystallize an active pharmaceutical ingredient, probenecid, and to improve the crystal qualities such as crystal habit and particle size characteristics. To screen the appropriate solvent system, solubility data of probenecid in organic solvent are measured, reported, and correlated by van't Hoff equation. According to the measured solubilities and data acquired from literature, sonocrystallization experiments using solvents with acceptable theoretical recovery are performed. Owing to the satisfactory throughput, yield, and crystal qualities, ethanol is finally decided as the appropriate solvent system. The effect of operating parameters in sonocrystallization including the solution concentration, sonication intensity, sonication duration, and cooling rate using ethanol as the solvent is further studied. With applying power ultrasound, probenecid crystals with narrow size distribution, regular crystal habit, and mean size around 15 µm are successfully produced. Finally, crystal form and spectroscopic property of sonocrystallized sample and probenecid as received from the supplier are compared and confirmed consistent from the analytical results of powder X‐ray diffractometer and Fourier transform infrared spectroscopy.

中文翻译：

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冷却声结晶法制备活性药物成分的粒径和晶体习性：丙磺舒的案例研究

这项研究使用冷却的超声波结晶工艺对活性药物成分丙磺舒进行重结晶，并改善晶体质量，例如晶体习性和粒度特征。为了筛选合适的溶剂系统，可以测量，报告丙磺舒在有机溶剂中的溶解度数据，并通过van't Hoff方程进行关联。根据测得的溶解度和从文献中获得的数据，进行使用可接受的理论回收率的溶剂进行声结晶实验。由于令人满意的生产量，产率和晶体质量，乙醇最终被确定为合适的溶剂体系。操作参数对声结晶的影响，包括溶液浓度，超声强度，超声持续时间，进一步研究了以乙醇为溶剂的冷却速度。通过施加功率超声，可以成功生产出尺寸分布窄，晶体习惯规则，平均粒径约15 µm的丙磺舒晶体。最后，比较了从供应商处获得的超声结晶样品和丙磺舒的晶形和光谱性质，并与粉末X射线衍射仪和傅里叶变换红外光谱法的分析结果相一致。