Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, Pharmacy and Bank Building A15, The University of Sydney, NSW 2006, Australia.
Hangzhou Chance Pharmaceuticals, Hangzhou, China.
Int J Pharm. 2020 Dec 15;591:119984. doi: 10.1016/j.ijpharm.2020.119984. Epub 2020 Oct 16.
Lactose is widely used as an approved excipient for dry powder inhaler (DPI) products. Spray drying technique is a rapid method for converting a liquid feed into inhalable dried particles. However, spray-dried (SD) lactose powders produced from solutions are mostly amorphous and particularly unstable when exposed to moisture. In the present study, we explored the use of spray drying suspensions containing crystalline lactose particles in an organic solvent, and investigated the physicochemical properties of the resulting powders. The solution formulation was spray dried as a control. Two conditioned crystalline lactose samples were used for suspension formulations: Lactohale (LH) 300 lactose and jet-milled (JM) lactose micronized from LH300. The suspension formulations each contained 12 mg/ml suspended crystalline lactose particles (either LH300 or JM lactose) in isopropyl alcohol. The solution formulation contained 60 mg/ml lactose in water. The SD powders were stored under 25 °C/60% RH and 40 °C/75% RH for 3 months. The particulate properties and in vitro dispersion performance were examined at various time points. The SD lactose obtained from solution recrystallized and was no longer dispersible after 1-day storage at both storage conditions. The suspension SD JM lactose powder showed deterioration in the particulate properties and dispersibility over time, but more gradually. In contrast, the SD LH300 powder was stable, with its particulate properties and dispersion performance (FPF: ~12%) remaining the same after 3-months storage at 25 °C/60% RH. The SD LH300 stored at 40 °C/75% RH showed no change in particulate properties, but the FPF decreased over 3 months. Overall, SD lactose powders obtained from suspension demonstrated superior stability performance compared to SD lactose obtained from solution.
乳糖被广泛用作干粉吸入剂（DPI）产品的批准赋形剂。喷雾干燥技术是一种将液体饲料转化为可吸入干燥颗粒的快速方法。然而，从溶液中喷雾干燥（SD）的乳糖粉末大多是无定形的，当暴露于水分时特别不稳定。在本研究中，我们探索了使用含有结晶乳糖颗粒的喷雾干燥悬浮液的方法，并研究了所得粉末的物理化学性质。该溶液制剂作为对照进行喷雾干燥。两种条件结晶乳糖样品用于悬浮液配方：Lactohale（LH）300 乳糖和从 LH300 微粉化的喷射磨（JM）乳糖。悬浮液配方各含有 12mg/ml 悬浮结晶乳糖颗粒（LH300 或 JM 乳糖）在异丙醇中。溶液配方含有 60mg/ml 乳糖在水中。SD 粉末在 25°C/60%RH 和 40°C/75%RH 下储存 3 个月。在不同时间点检查 SD 粉末的颗粒特性和体外分散性能。从溶液中获得的 SD 乳糖重新结晶，在两种储存条件下储存 1 天后不再可分散。随着时间的推移，悬浮 SD JM 乳糖粉末的颗粒特性和分散性逐渐恶化，但更缓慢。相比之下，SD LH300 粉末是稳定的，其颗粒特性和分散性能（FPF：~12%）在 25°C/60%RH 下储存 3 个月后保持不变。在 40°C/75%RH 下储存的 SD LH300 粉末的颗粒特性没有变化，但 FPF 在 3 个月内下降。总体而言，与从溶液中获得的 SD 乳糖粉末相比，从悬浮液中获得的 SD 乳糖粉末表现出更好的稳定性。
