Gelation Phenomenon and Its Regulation Strategy of Tilmicosin Phosphate

Amorphous tilmicosin phosphate (TMP) suffers from low stability, and its crystalline product is not reported. At the same time, the gelation phenomenon often occurs in the crystallization process of TMP, which seriously affects the robustness of the process and product quality. In this paper, a crystal form of TMP was developed, and it was determined to be tilmicosin phosphate trihydrate by powder X-ray diffraction, thermogravimetric differential scanning calorimetry, Fourier transform infrared (FTIR), and Karl Fischer water content test. Besides, the gelation phenomenon and the gel transition process during TMP crystallization were studied by spectroscopic and microscopic methods. The results show that TMP gel is an intermediate form formed by amorphous TMP and solvent, and the type of solvents and water content in these solvents were important factors affecting the gelation and crystallization behavior of TMP. Finally, the TMP crystallization process was optimized, and trihydrate of TMP could be obtained directly without passing through the intermediate gel state. It was found that, after process optimization, the particle size, crystallinity, and stability of the obtained crystal products were improved.