(449aa) Mechanism and Kinetics of the Polymorphic Transportation from Amorphous to Hydrate of Disodium Guanosine 5′-Monophosphate

Zou, F., Nanjing Tech University
Chen, Q., Nanjing Tech University
Yang, P., Nanjing Tech University
Zhuang, W., Nanjing Tech University
Wu, J., Nanjing Tech University
Ying, H., Jiangsu National Synergetic Innovation Center for Advanced Materials
Polymorphism is a key factor in the development of the process for pharmaceutical and fine-chemical manufacture. Different polymorphs may contribute to different functionalities and physical properties, such as bioavailability, stability, solubility and morphology of the particles, etc. Hence, it is essential to investigate the mechanism of polymorphic transformation and transformation kinetics, which can guide us to obtain the desired polymorph in industry.

The aim of this work was to investigate the mechanism of the solution-mediated transformation (SMT) from amorphous to hydrates of disodium guanosine 5â?²-monophosphate in ethanol. The polymorphic transformation was monitored by four in situ analytical techniques, the Focused beam reflectance measurement (FBRM) and particle vision and measurement (PVM) have been used to track the chord length and morphology; the Raman spectroscopy was used to detect the polymorphic form in transformation process, while attenuated total reflection Fourier transformation infrared (ATR-FTIR) spectroscopy was used to measure the liquid-phase concentration profile. The transformation follows a SMT mechanism in solution.

The SMT process includes five important process: metastable polymorph nucleation and growth, dissolution and stable polymorph nucleation and growth. A series of seeded transformation experiments, the effect of different operating condition on the transformation was studied. The seed mass and pH is key factor in all operation condition, both increasing seed mass and value of pH decrease the transformation time, and indicating that a seed-based secondary nucleation mechanism of the stable polymorph.

Also some independent seeded batch desuperstauration experiments were conducted to determine the kinetics of the five different process for both polymorphs. Furthermore the popular balance model was also used to calculate the kinetics to identify the determining step in the polymorph transformation process.


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