Solvent Dynamics and Thermodynamics at the Crystal–Solution Interface of Ibuprofen

Abstract

The choice of solvent is key in the manufacturing of solution-grown crystals due to the critical effect it can exert on their morphology. Here we set out to investigate the dynamics and thermodynamics of solvent molecules at the crystal-solution interface for the morphologically dominant crystal faces of ibuprofen. In particular, we evaluate how thermodynamically favourable the desorption of a solvent molecule is and estimate the rate of exchange of adsorbed solvent molecules with molecules from the bulk solution. This analysis is carried out for all four morphologically dominant crystal faces of ibuprofen {100}, {002}, {011} and {110}, and ten solvents, i.e. water, 1-butanol, toluene, cyclohexanone, cyclohexane, acetonitrile, trichloromethane, methanol, ethyl acetate and ethanol. Our work reveals that the structure of the solution and the exchange dynamics can be strongly dependent on both the crystal face and the solvent, i.e. the same solvent can show radically different structure when in contact with different faces, alternatively the same face can induce different structuring in different solvents. Moreover, we find particularly strong surface-solvent interactions for the {002} and {100} crystal faces in several of the solvents examined. We conclude that the role of desolvation in the growth process is solvent-and face-specific, and therefore it has the potential of impacting the crystal shape anisotropy. We provide a framework to rationalise this effect based on molecular simulations of the crystal/solution interface.

Solvent-Induced, Highly Unusual, Triangular-Shaped Organic Polar Crystal

“…The computational model based on MD simulations was developed to facilitate the understanding of crystal–solvent interfaces. ,− In this study, MD simulations were performed to investigate the behavior of toluene molecules at the crystal–solvent interfaces of (001) and (00) during the crystallization. As shown in Figure a, the simulation cell comprises a crystal lamina of BCA with the face (001) (−OH groups) and (00) (−OCH 3 groups) exposed to toluene.…”

On the Role of Solvent in the Formation of Vacancies on Ibuprofen Crystal Facets

“…7, we plot the work of defect formation as a function of the solvent residence time at the interface obtained and reported in detail in Ref. 11 Assessing Fig. 7, a very prominent linear correlation between the residence time of a solvent molecule at the crystal surface and the work required to form a surface vacancy, particularly for the {002} and {011} crystal facets, can be noted.…”

“…The {110} is occasionally also considered as a morhphologically dominant crystal face, but was excluded from the analysis in this study due to its generally rough nature and tendency for spontaneous surface roughening and dissolution, indicating a comparably lower barrier to the process of interest and therefore, lower morphological importance. 11,13…”

“…In previous work 11 we demonstrated how surface-solvent interactions have the ability to affect the surface roughness as well as the solvent behaviour at the crystal surface, which, in turn will play an important role in the processes of incorporation or detachment of growth units from the crystal surface. Moreover, internal conformational rearrangements of the solute are typically present, and can be dependent on both the crystal face and the solvent.…”

“…7 Solvent polarity, steric interactions and hydrogen bonding capabilities have also been found to affect the growth rate of specific crystal facets, 8,9 while in some cases Coloumb and Van der Waals forces can have a significant impact. 10 In out recent work, 11 the dynamics and thermodynamics of solvent molecules at the crystalsolution interface reveal how the type, strength and lifetime of surface-solvent interactions can have a dramatic impact on the solvent behaviour at the crystal surface. Quantifying this information has provided a straightforward and easily accessible screening procedure of identifying solvents which have the potential to affect crystal shape anisotropy.…”