Influence of the Solvent Content on the Phase Transformation of Sulfadiazine N‐Methyl Pyrrolidone Solvate

• Published in: Chemical engineering & technology Vol. 42; no. 7; pp. 1435 - 1445
• Main Authors: Macaringue, Estevao G. J., Wu, Songgu, Liu, Shiyuan, Xu, Shijie, Gong, Junbo
• Format: Journal Article
• Language: English
• Published: Frankfurt Wiley Subscription Services, Inc 01.07.2019
• Subjects: Aggregate; Phase transformation; Phase transitions; Raman spectroscopy; Reflectance; Scanning electron microscopy; Single crystal; Single crystals; Solvate; Solvents; Sulfadiazine
• ISSN: 0930-7516; 1521-4125
• DOI: 10.1002/ceat.201800738

The influence of the solvent content on the solution‐mediated phase transformation of sulfadiazine (SD) N‐methyl pyrrolidone (NMP) solvate into SD was investigated for process development. The solubility results of the NMP solvate and SD in NMP solvent/water mixtures supported by the analysis of solvent‐solvent interactions between NMP solvent molecules were used to understand and optimize the transformation of the NMP solvate into SD. Needle‐on‐rhombic‐like aggregated crystals and rod‐like single crystals of SD were obtained and reported for the first time. By combining Raman spectroscopy, focused‐beam reflectance measurements, and scanning electron microscopy, the phase transformation of NMP solvate into SD was tracked. Higher temperatures and stirring rates accelerate the transformation process and have a negative influence on the final SD product quality. Finer powders of poorly soluble drugs provide better bioavailability and are therefore preferred by the pharmaceutical industry. In the solution‐mediated phase transformation of sulfadiazine (SD) N‐methyl pyrrolidone (NMP) solvate into SD, the NMP amount influences the crystal structure while higher temperatures and stirring rates accelerate the transformation process, negatively influencing the product quality.