Characterisation of the Crystal-Solution Interface during Growth and Dissolution using Laser Interferometry

Growth and dissolution models are often based on bulk solution properties and hence do not implicitly consider the influence of concentration variation close to the crystal–solution interface and how this is mediated by solute diffusive mass transfer. A novel, dual interferometric system is developed and applied to examination of growth and dissolution on the crystal habit surfaces of the organic materials ˪-alanine and paracetamol. The {120} and {011} crystal surfaces of ˪-alanine and the {001} surface of paracetamol were found to be below saturation during growth and dissolution. The growth process is found to be rate-limited by the kinetics of surface integration rather than mass transfer for all supersaturations examined and to the same degree, whereas the dissolution process exhibits a mixed dependency on surface kinetics and mass transfer.

Boundary layer thicknesses for ˪-alanine and paracetamol increase with super/undersaturation but to a lesser degree than the concentration differences between the crystal surfaces and bulk solutions leading to a higher mass flux of solute molecules through the boundary layer. At the same relative super/undersaturation, mass flux of solute molecules was faster during the dissolution process when compared to the growth process. This, coupled with the faster surface kinetics during dissolution, indicates that detachment of solute molecules at the crystal/solution interface is easier than their attachment under the same relative driving force for growth or dissolution.

The {011} surface of ˪-alanine displays faster growth and dissolution kinetics and a larger concentration difference between the crystal surface and bulk solution than the {120} surface reflecting its polar nature and stronger solute binding energy. The edge between the {011} and {120} faces of ˪-alanine shows characteristics of faster dissolution but slower growth. The {001} face of paracetamol has a surface solute concentration closer to saturation at much higher super/undersaturations than observed for ˪-alanine reflecting paracetamol’s lower aqueous solubility and weaker binding of this surface to the solution phase.

This calculation of the mass flux and combination of this together with accurately measured kinetics provided an important step in the development of new, more accurate crystal growth and dissolution models. This can have implications for the development of poorly soluble APIs as well as allowing for deeper elucidation into the fundamentals of growth and dissolution.