Hafner Anita, Dürrigl Marjana, Pepić Ivan, Filipović-Grčić Jelena
Department of Pharmaceutics, Faculty of Pharmacy & Biochemistry, University of Zagreb, Croatia.
Chem Pharm Bull (Tokyo). 2011;59(9):1117-23. doi: 10.1248/cpb.59.1117.
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.
本研究的目的是建立一种用于负载褪黑素的卵磷脂/壳聚糖纳米颗粒（NPs）的冷冻干燥工艺，以在更长时间内保持其化学和物理稳定性，这在水悬浮液中是无法实现的。在NP悬浮液的冷冻干燥过程中，研究了葡萄糖和海藻糖作为潜在的赋形剂。卵磷脂/壳聚糖NPs通过平均直径和zeta电位进行表征，根据制备中卵磷脂类型和壳聚糖含量的不同，平均直径在117.4至328.5 nm之间，zeta电位在6.7至30.2 mV之间。褪黑素负载量高达7.1%。对于所有卵磷脂/壳聚糖NPs，在冻干过程之前或之后立即以及在4℃储存7个月后，未观察到平均粒径、粒径分布、zeta电位或褪黑素含量有明显差异。冻干后立即含有葡萄糖和海藻糖的冻干物的残留水分含量分别在4.0 - 4.8%和2.4 - 3.0%之间。如调制差示扫描量热法所示，所有卵磷脂/壳聚糖NPs在冷冻干燥过程后均具有完全无定形的性质。含有葡萄糖的NP冻干物具有较低的玻璃化转变温度（约5℃），这证实了以葡萄糖作为冷冻保护剂进行冻干是不合适的。所有含有海藻糖的冻干物的玻璃化转变温度均高于室温，能够形成块状物而不会出现结构坍塌，并且在4℃储存7个月后仍能保持其特性和外观。
