Carvedilol precipitation by combined antisolvent-cooling crystallization was performed in the presence of polyvinylpyrrolidone (PVP) of different molecular weight. Drug emulsion was formed as a result of water addition and crystal growth occurred after cooling. In the absence of the additive, the kinetically preferred Form II polymorph crystallized while PVP facilitated the formation of the thermodynamically stable Form III (hemihydrate) polymorph. Crystallization was monitored by real-time Raman spectrometry to indicate the polymorphic form and the endpoint of the process. The thermodynamic relationship between these polymorphs was established also by real-time Raman spectrometry using ethanol and water as solvent mixture. In all cases, just a small amount of PVP, adsorbed on the crystal surface, was sufficient to affect the crystal form advantageously and induce excellent flowability of the products. The modification of crystal morphology assisted by the applied additives is ascribed to the altered way of crystal growth.
- Inline monitoring
- Raman spectrometry
ASJC Scopus subject areas
- Chemical Engineering(all)
- Industrial and Manufacturing Engineering