Continuous Heterogeneous Crystallization on Excipient Surfaces

Abstract

A novel continuous heterogeneous crystallization process is developed in which the active pharmaceutical ingredient (API) is crystallized directly on the surface of an excipient within the crystallizer. The product is subsequently dried and formed into tablets without the need for complex downstream processing steps, such as milling, sieving, granulation, and blending. The aim is to eliminate many steps of the particle processing in drug product manufacturing. The APIs and excipients systems were selected by investigating heteroepitaxial mechanisms. The effects of various process parameters, such as temperature, residence time, and mode of operation, on drug loading were studied. Three different process designs—mixed suspension mixed product removal with a traditional impeller, Viscojet mixing, and a fluidized bed crystallizer—were utilized for direct crystallization of the API on the surface of the crystalline excipient. The excipient selection and process design parameters have a significant impact on d...