Impact of Impurities on Crystallization and Product Quality: A Case Study with Paracetamol

A thorough, systematic study into the effect that structurally related impurities have on both process and product quality during crystallization of an active pharmaceutical ingredient is presented. The presence acetanilide metacetamol influences paracetamol. Where high concentrations either impurity were present in feed, recovery decreased by up to 15%. Acetanilide included final through adsorption onto particle surface 0.79 mol%, which can be reduced acceptable levels reslurrying. results much higher concentrations—up 6.78 mol% product, approximately 1 incorporated crystal lattice, resulting perturbation unit-cell dimensions. incidental subsequent isolation metastable Form II paracetamol increased purity a low concentration. This converts stable I reslurrying, offering efficient rejection route. morphology modified consistently impurities. An elongation normal prismatic shape observed, extreme case contamination fine, fragile needles. problematic also improved reslurrying give more equilateral shape. influence builds well-rounded picture concomitant impact principal attributes product.