Agglomeration is an important phenomenon which often controls the particle size distribution and morphology in the crystallization of organic compounds. In this thesis the influence of solvent composition on crystal agglomeration of paracetamol is investigated.
Particles from (i) isothermal desupersaturation experiments with initiated nucleation and (ii) fully seeded isothermal crystallization experiments operating at constant supersaturation have been characterized. The number of crystals in each particle has been determined by image analysis using multivariate data evaluation and a set of calibration particles. A parameter defining the degree of agglomeration is extracted from the number distribution of crystals per particle. In addition, the agglomerate strength determined by the crushing of single agglomerates has been measured.
The results clearly show that the solvent composition has an influence on the crystal agglomeration. This observed influence cannot be explained by differences in the solution viscosity (fluid mechanics), or by differences in the overall crystal growth rate. The product is less agglomerated and the agglomerates are weaker when the crystallization is carried out in a more polar solvent, e.g. water. In the systems studied, a high solvent polarity coincides with hydrogen-bond-donating and hydrogen-bond-accepting capabilities. These solvents can interact strongly with paracetamol crystal surfaces which exhibit both donating and accepting sites. In less polar solvents like acetone, only donating sites on the surfaces can be occupied.
Surfaces of large, well-grown paracetamol crystals have been characterized by contact angle measurements according to the Lifshitz-van der Waals acid-base theory. The surface free energy varies between 50-57 mJ/m2, and all faces indicate a strong hydrogen-bond acceptance.
The free energy of adhesion between crystal faces in different solvents has been calculated from the surface free energy components. The findings in this thesis strongly support the hypothesis that the mechanism by which the solvent influences on the agglomeration relates to the molecular interaction at the crystal-solvent interface and the physico-chemical adhesion forces between crystal faces in the solution.
2005. , xii, 61 p.
2005-05-20, D2, KTH, Lindstedtsv. 5, Stockholm, 13:00