Pharmaceutical crystal shape control based on online image processing and multi-scale modelling

Abstract

Pharmaceutical crystals grown from solution are known to exhibit multiple morphological forms and habits which are of great importance to the end use properties of the product such as the bioavailability and down stream processing such as filtration and drying. The crystal morphology can also dictate other quality measures such as size. This paper reviews recent developments in online crystal morphology measurement and control using online imaging and image analysis. Online imaging was found to be able to capture with high fidelity crystal shape and polymorphic transitions in real-time. The images were analysed using a multi-scale image analysis method to extract the crystals from the image background. Preliminary results on estimating crystal growth rates and kinetics parameters for different facets for rod-like crystals were presented. The paper also reviews recent developments in morphological population balance (PB) modelling which can provide the evolution of the shape and distributions of sizes in all crystal face directions in a reactor. Finally, the perspectives for automatic morphology control which require integration of crystal morphology prediction, morphological PB modelling, online 3D imaging and image analysis for shape characterisation as well as computational fluid dynamics are outlined.