[Real-time monitoring of drug crystallization with and without additives]

Crystallization processes can be evaluated from both kinetic and thermodinamic point of view with real-time analitical methods, effects of production parameters on the final quality can be estimated as well. Consequently there is an increasing emphasis on analytical devices being applicable for real-time detection. Among these techniques Raman spectrometry is advantageously utilizable for real-time monitoring of crystallizations. Impurities can dramatically change the nucleation and crystal growth, thus they can alter the physical and chemical properties of the final product. The use of different additives (polymers;surface active ingredients) in the crystallization step in order to modify the product morphology methodically is a new direction in the scientific literature. This study provides an overview of crystallization processes in the presence of additives as well as a summary concerning the monitoring of the drug crystallizations by real-time Raman spectrometry. Furthermore the effect of polyvinyl-pyrrolidone was examined in the course of cooling crystallization of Donepezil HCl, while the process was monitored by in-line Raman spectrometry.