title: Sugars as bulking agents to prevent nano-crystal aggregation during spray or freeze-drying.
abstract: 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.
authors.affiliation: University of Connecticut, School of Pharmacy, 69 North Eagleville Road, Storrs, CT 06269, USA.
authors.forename: Sumit
authors.initials: S
authors.lastname: Kumar
authors.affiliation: AbbVie Pte Ltd, Research and Development, 11 Biopolis Way, Helios, #05-06, Singapore 138667, Singapore.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Gokhale
authors.affiliation: University of Connecticut, School of Pharmacy, 69 North Eagleville Road, Storrs, CT 06269, USA. Electronic address: d.burgess@uconn.edu.
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Burgess
mesh_terms: D002152:Calorimetry, Differential Scanning; D002241:Carbohydrates / Q000737:chemistry*; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying; D007213:Indomethacin / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size
chemical_list: D002241:Carbohydrates; D005079:Excipients; D007213:Indomethacin
keywords: Freeze-drying; Nano-crystal powder; Nano-crystalline suspension; Spray-drying; Sugars