A mechanistic model for supersaturation and crystal growth during batch crystallization of organic solids from solutions containing multiple conformers is presented. The model is based on the approach of the right conformer (RC) which assumes that only one conformer participates in the surface integration step. The model is concerned with systems characterized by slow crystal growth and low supersaturation, a behavior favored when the RC is the minority species in solution. Crystal growth is assumed to occur via a step advance mechanism with a variable step advance velocity (VSAV). Model derivation indicated that when the approach of the RC applies, crystal growth is inversely proportional to crystal size. Lastly, model simulations predicted an exponential increase of maximum relative supersaturation with linear antisolvent addition rate. The simulation also allowed estimation of maximum addition rate below which secondary nucleation is minimized.
In this Article, the validity of a model derived for crystal growth rates and supersaturation for solids crystallized from solutions of materials containing multiple conformers is evaluated. A simple and straightforward method for determining crystal growth rates using FBRM and FTIR/ATR is utilized, which leads to a large amount of growth rate data from a single experiment. Supersaturation and crystal growth rate obtained experimentally were in good agreement with model predictions. In particular, data indicated that for the system at hand, crystal growth rate is inversely proportional to crystals size. Further, the solute integration coefficient determined from supersaturation measurements can be slightly overestimated due to surface nucleation and/or agglomeration that can result from supersaturation spikes during antisolvent addition. Last, crystal growth data obtained at different temperatures indicated that slow growth rate observed at low temperatures is likely to be due in part to surface poisoning by the wrong conformer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.