Sugars as bulking agents to prevent nano-crystal aggregation during spray or freeze-drying

摘要

In this study, the effect of low and high molecular weight sugars on indomethacin nano-crystalline suspension powders prepared by spray or freeze-drying was evaluated. Dowfax 2A1 (negatively charged surfactant) was utilized as indomethacin nanosuspensions stabilizer. Dried crystalline powders with or without sugars were characterized for crystallinity, particle size and powder yield. Interactions between the nanosuspension stabilizer (i.e. Dowfax 2A1) and sugars were investigated by utilizing IR spectroscopy and contact angle measurements. The nanosuspension formulations containing small molecular weight sugars were non-aggregating compared to those containing polysaccharides. Additionally, higher powder yields were observed with formulations containing sugars with higher glass transition temperature during spray drying. The formulations containing low glass transition temperature sugars were sticking to the spray drier glass walls and thus resulted in lower yields. The small molecular weight sugars showed favorable interactions with Dowfax 2A1, as evident by the IR and contact angle data, possibly resulting in minimal nano-crystal aggregation during spray or freeze-drying. A combination of sugars (i.e. small molecular weight and polysaccharides) may be utilized to achieve higher spray-drying yields and non-aggregating nano-crystalline powders. Published by Elsevier B.V.