The Evolution of Crystal Shape During Dissolution: Predictions and Experiments

Abstract

ࠗ w This paper contains enhanced objects available on the Internet at http://pubs.acs.org/crystal. ABSTRACT: A comparison between a priori model predictions and experimental results for crystal shapes of succinic acid crystals dissolving in aqueous solution is presented. The model is the simplest possible model which neglects all effects other than a determination of which faces to include on the crystal habit and their perpendicular growth rates. The experiments are carried out in a thermostatted peltier cell and are imaged in situ using a microscope with digital imaging capabilities. The predicted and experimentally measured crystal shapes are very similar throughout the dissolution process. Thus, the experiments provide support for the model's predictive power.The change in crystal shape as a result of dissolution is a topic of interest for a wide range of materials including organics such as pharmaceuticals, proteins and specialty chemicals as well as inorganics in geology and semiconductors. For inorganic and organic materials, dissolution not only affects the crystal shape but also plays a vital role in polymorphic phase transformations. The possible end-shapes in crystal dissolution have been discussed in many contexts. 1-4 For example, Moore suggested that vertices on growth shapes would end up as faces on dissolution shapes, 2 and Gibbs suggested that shapes in dissolution will differ from the equilibrium form in a direction "opposite" to that of growth. 3 Despite these qualitative descriptions, a model that can quantitatively predict the evolution of crystal shapes during dissolution has only recently been developed. 5 This communication presents recently produced in situ experimental confirmation of the model's predictions for the dynamics of dissolving crystal shapes, along with the related modeling information necessary for comparison.We have chosen -succinic acid crystals dissolving in water as the system to demonstrate the effective predictions of the model. The crystallization and subsequent dissolution and visualization were performed in a thermostatted peltier cell equipped with a Nikon microscope and digital imaging capabilities, and has been previously described in detail. 6 A saturated solution of -succinic acid 7 in 2 mL of water was prepared at a saturation temperature of 36°C. Nucleation was induced at a lower temperature (25°C). Once a crystal could be observed in the solution, the temperature was raised to within a degree of saturation, and the crystal was allowed to grow to a size suitable for dissolution visualization (∼100 µm). Then, the temperature was increased to one degree above saturation, leading to dissolution during which the crystal shape evolution was recorded. Since the mass of the dissolving crystal is very small (∼0.001 mg compared to the 2 mL volume of the crystallizer) the undersaturation is approximately constant throughout the dissolution process.The model for shape evolution can predict and track each of the faces of a fully three-dimensional crystal during growth an...

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution

“…27,28 This knowledge of anisotropic dissolution behaviour of single crystals can highlight the factors 6 affecting crystal dissolution, which is crucial in the design, evaluation and control of therapeutic efficacy of solid dosage forms. 29,30 Due to the complexity arising from the multi-component nature of pharmaceutical cocrystals, it is expected that the knowledge from single component crystals needs to be rigorously validated and further extended when applied to the dissolution of cocrystals. The present work, for the first time, is aimed at understanding the dissolution mechanisms of cocrystals in solution in the absence and presence of a pre-dissolved polymer.…”

Controlling and Predicting Crystal Shapes: The Case of Urea

“…Since the interaction of crystals with their environment occurs through their surface, their shape controls a wide variety of properties. [1][2][3] This is particularly important not only in nanotechnology, where shape-function relations play a key role, but also in medicine where changing the morphology of particles allows for instance for a better targeting of cancer cells. [4] In this work we combine experiments, molecular simulations, and theory to examine the morphology of urea crystals grown in different solutions.…”

Measurement, modelling, and closed-loop control of crystal shape distribution: Literature review and future perspectives

“…In literature, the so-called multidimension is often interpreted as multiple-variables, i.e., a single-size dimension as volume equivalent spherical diameter plus other variables, such as particle location, porosity and fraction ratio. Crystal morphology has been a very important research area, but the focus has been on shape prediction for single crystals [10,[75][76][77][78][79][80] rather than for all the crystal population within a crystalliser. On the other hand, although population balance (PB) modeling for crystallisation processes is for all crystals in a crystalliser, crystal shape was often ignored with an over-simplified crystal-size definition, i.e., the volume equivalent diameter of spheres (see for example [54,[81][82][83][84][85][86][87][88]).…”

“…Considering the length of the paper, a full review on how to construct accurate and reliable kernels for nucleation (homogeneous and heterogeneous), and dissolution and Oswald ripening is not included here. Readers are directed to literature [15,79,109,110].…”