Mechanisms of Crystal Agglomeration of Paracetamol in Acetone−Water Mixtures

The mechanisms governing the influence of the solvent composition on the agglomeration in a crystallization process have been investigated. Narrowly sieved paracetamol crystals were suspended in supersaturated acetone−water solutions, and were allowed to grow at isothermal conditions, after which the agglomeration was recorded. In all experiments the same sieve size fraction was used as well as the same magma density. In each experiment the supersaturation was kept constant. Experiments were performed in different solvent compositions at different supersaturation, crystal growth rate, solution viscosity, and agitation rate. For a statistically sufficient number of particles from each experiment, the number of crystals in each product particle was determined by image analysis and multivariate data evaluation. From the resulting number distributions of crystals per product particle, parameters defining the “degree of agglomeration” were extracted. The experimental results clearly establish that there is an influence of the solvent composition on the degree of agglomeration, which cannot be explained by differences in crystal growth rate, or differences in solution viscosity. The degree of agglomeration is found to decrease with increasing solvent polarity. It is suggested that the mechanism by which the solvent influence relates to the crystal−solvent interaction and the physicochemical adhesion forces between crystals in the solution.