Evaporative crystallization is widely used in various manufacturing processes, which concentrate organic or inorganic solutions by solvent evaporation above supersaturation limits. Controlling the evaporation process and the uniformity of crystals still remain the critical issues in this type of unit operation. Particularly, for drug crystals for orally disintegrating films or crystal layers for electrical and optical applications, the fabrication of uniform crystals is highly preferable. However, it is quite difficult to constantly control evaporation rates, uniformly throughout the surfaces of solutions with minimizing random fluctuation. In this study, an evaporation rate was uniformly maintained by controlling the critical parameters such as thermal gradient and flow rate of air, resulting in the formation of well-aligned crystals of uniform morphologies. We chose acetaminophen as a model compound, and various polymers were used as additive for polymer-directed crystallization. It was found to be important to control the nucleation behavior in the solution. The morphology of acetaminophen crystals significantly depends on evaporation rate, type and composition of polymers. It changed from triangular to rod shape with increasing the content of ethyl cellulose. The crystal faces of acetaminophen grow more dominant or limited state because the arrangement of acetaminophen molecules was transformed depending on the functional group of polymers. Selective etching process could dissolve only acetaminophen or polymers, resulting in patterned polymeric materials or acetaminophen crystals with regular and unique patterns. These patterns could be related with the sub-micron structures of acetaminophen and polymers. As a result, controlling the structures of composite crystals could help us to develop the engineering strategy of future functional crystals such as orally disintegrating film.

Evaporative crystallization of drug with limited air flow for preparation of uniformly aligned composite crystals

2019 Fall National Meeting

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