title: Short- and long-term stability of lyophilised melatonin-loaded lecithin/chitosan nanoparticles.
abstract: The aim of this study was to establish a freeze-drying process for melatonin-loaded lecithin/chitosan nanoparticles (NPs) to preserve their chemical and physical stability for a longer time period that what is possible in an aqueous suspension. Glucose and trehalose were investigated as potential excipients during freeze-drying of NP suspensions. Lecithin/chitosan NPs were characterised by mean diameter and zeta potential, ranging between 117.4 and 328.5 nm and 6.7 and 30.2 mV, respectively, depending on the lecithin type and chitosan content in the preparation. Melatonin loadings were up to 7.1%. For all lecithin/chitosan NPs, no notable differences in the mean particle size, size distribution, zeta potential or melatonin content were observed before or immediately after the lyophilisation process or after 7 months of storage at 4 °C. The residual moisture contents of lyophilisates with glucose and trehalose immediately after the lyophilisation process varied between 4.0-4.8% and 2.4-3.0%, respectively. All lecithin/chitosan NPs had a fully amorphous nature after the freeze-drying process, as indicated by modulated differential scanning calorimetry. NP lyophilisates with glucose had a low glass transition temperature (ca. 5 °C), confirming that lyophilisation with glucose as a cryoprotectant was not appropriate. All lyophilisates with trehalose had a glass transition temperature above the room temperature, allowing formation of the cake without a collapse of the structure, which was capable of preserving its characteristics and appearance following 7 months of storage at 4 °C.
authors: Department of Pharmaceutics, Faculty of Pharmacy & Biochemistry, University of Zagreb, Croatia. ahafner@pharma.hr
authors: Anita
authors: A
authors: Hafner
authors: Marjana
authors: M
authors: Dürrigl
authors: Ivan
authors: I
authors: Pepić
authors: Jelena
authors: J
authors: Filipović-Grčić
mesh_terms: D002152:Calorimetry, Differential Scanning; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D005612:Freeze Drying; D005947:Glucose / Q000737:chemistry; D054709:Lecithins / Q000737:chemistry*; D008550:Melatonin / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D044366:Transition Temperature; D014199:Trehalose / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D054709:Lecithins; D048271:Chitosan; D014199:Trehalose; D005947:Glucose; D008550:Melatonin