Crystallo-co-spray drying as a new approach to manufacturing of drug/excipient agglomerates: impact of processing on the properties of paracetamol and lactose mixtures.

Abstract

The novel process of crystallo-co-spray drying of paracetamol and α-lactose monohydrate was investigated by varying the spray dryer inlet temperature and inlet feed solvent composition. A crystalline agglomerate was obtained with no change to the physical structure of either component throughout both investigations and with possible interactions between the hydroxyl groups of the α-lactose monohydrate and the amide and hydroxyl groups of the paracetamol detected. The percentage soluble fraction of the components in the inlet feed had the largest influence on the morphology of the final dried agglomerate. Low excipient soluble fraction resulted in an increase in paracetamol surface coating and high excipient soluble fraction produced agglomerates of highly mixed components. The use of crystallo-co-spray drying can serve as a method of producing an agglomerated blend of crystalline co-spray dried components leading to possible opportunities for process intensification with the reduction of process steps such as blending, agglomeration, drying and milling into one single stage.