Tazobactam as the third generation antibacterial synergist presented the low toxicity and a wider antimicrobial spectrum, and dominated in clinical application. Tazobactam sodium powder as pharmaceutical form was usually prepared by lyophilization in the pharmaceutical industry, which was extremely hygroscopic and required strict storage conditions. In this work, we prepared four new polymorphs of tazobactam sodium by antisolvent methods, and optimized the crystallization process. Among them, the single crystal of tazobactam sodium in water/ethanol solvent was obtained and the structure was analyzed. Further, reactive crystallization process was explored and optimized, including amine reagent, salt-forming agent and solvent system. The current work provided more options for the pharmaceutical polymorphs of tazobactam sodium, supporting the industrial production and transportation of the drug.

他唑巴坦作为第三代抗菌增效剂，具有毒性低、抗菌谱广等特点，在临床应用中占据主导地位。作为药物剂型的他唑巴坦钠粉末在制药工业中通常通过冻干法制备，具有极强的吸湿性和对储存条件的严格要求。在这项工作中，我们通过反溶剂法制备了他唑巴坦钠的四种新晶型，并优化了结晶工艺。其中，获得了他唑巴坦钠在水/乙醇溶剂中的单晶，并进行了结构分析。此外，探索和优化了反应结晶工艺，包括胺试剂、成盐剂和溶剂体系。目前的工作为他唑巴坦钠的药物晶型提供了更多的选择，