(286g) Continuous Heterogeneous Crystallization of Active Pharmaceutical Ingredients on Excipients Surfaces

Novel continuous heterogeneous crystallization processes were developed, which the active pharmaceutical ingredient is crystallized directly on the surface of an excipient within the crystallizer. The product is then dried, and formed into tablets without the need for complex downstream processing steps such as milling, sieving, granulation, and blending. The APIs and excipients systems selected by study of heteroepitaxial mechanisms, and surface functionality of substrate. The effect of various process parameters, such as temperature, residence time, mode of operation, and excipient loading were studied. Three different process types in two categories of direct crystallization on surface of crystalline excipient and on surface of a carefully selected polymer (with surface modification) were studied. The excipient selection, and process parameters design have significant impact on drug loading, avoiding bulk nucleation and crystallization, control of API crystals shape and size, and control of process. In general, a decrease in temperature as well as the increase in residence time, both increased the drug loading of excipient with API. Within the range of our analysis, proportional drug loading can be easily tailored for a wide range depending on required drug dosage per tablet. The fully continuous processes, and eliminating the downstream steps result in producing crystalline compounds and final form (tablets) in significantly faster, more efficient, with lower footprint, and more economical.