Advanced Drug Delivery Group, School of Pharmacy, University of Sydney, Sydney, NSW, Australia.
Advanced Drug Delivery Group, School of Pharmacy, University of Sydney, Sydney, NSW, Australia.
Int J Pharm. 2021 Jun 1;602:120608. doi: 10.1016/j.ijpharm.2021.120608. Epub 2021 Apr 20.
Spray drying is a rapid method for converting a liquid feed into dried particles for inhalation aerosols. Lactose is a major inhalation excipient used in spray-dried (SD) formulations. However, SD powders produced from solutions are usually amorphous hence unstable to moisture. This problem can potentially be minimized by spray drying a suspension (instead of solution) containing crystalline lactose particles and dissolved drugs. In the present study, the suspension formulation containing dissolved budesonide (BUD) or rifampicin (RIF) and suspended lactose crystals in isopropanol alcohol (IPA) were produced. For comparison, powders were also produced from solution formulations containing the same proportions of drug and lactose dissolved in 50:50 IPA/water as controls. These SD powders were stored at 25 °C/60% RH and 40 °C/75% RH for six months. The particulate properties and in vitro dispersion performance were examined at various storage time points. All powders obtained from spray drying of solutions recrystallized after one week of storage at 25 °C/60% RH. In contrast, SD BUD-lactose obtained from suspension did not change until after three-months of storage when the particle size increased gradually with morphology change and yet the crystallinity remained the same as determined by X-ray powder diffraction. For the SD RIF-lactose obtained from suspension, both particulate properties and in vitro powder dispersion performance showed no significant difference before and after storage at both storage conditions. To conclude, this is the first study to show that SD powder formulations obtained from suspensions containing lactose crystals demonstrated superior storage stability performance, which is desirable for inhaled powders.
喷雾干燥是一种将液体饲料转化为吸入气溶胶干燥颗粒的快速方法。乳糖是用于喷雾干燥（SD）制剂的主要吸入赋形剂。然而，从溶液中生产的 SD 粉末通常是无定形的，因此对水分不稳定。通过喷雾干燥含有结晶乳糖颗粒和溶解药物的悬浮液（而不是溶液）可以最小化这个问题。在本研究中，制备了含有溶解布地奈德（BUD）或利福平（RIF）和异丙醇（IPA）中悬浮乳糖晶体的悬浮液制剂。为了进行比较，还从含有相同比例药物和乳糖的溶液制剂中制备了粉末，这些药物和乳糖溶解在 50:50IPA/水中作为对照。将这些 SD 粉末在 25°C/60%RH 和 40°C/75%RH 下储存 6 个月。在不同的储存时间点检查颗粒特性和体外分散性能。在 25°C/60%RH 下储存一周后，从溶液喷雾干燥获得的所有粉末均重新结晶。相比之下，从悬浮液中喷雾干燥获得的 SD BUD-乳糖在储存三个月后才发生变化，此时粒径逐渐增大，形态发生变化，但结晶度仍与 X 射线粉末衍射确定的相同。对于从悬浮液中获得的 SD RIF-乳糖，在两种储存条件下储存前后，颗粒特性和体外粉末分散性能均无明显差异。总之，这是第一项表明含有乳糖晶体的悬浮液中获得的 SD 粉末制剂表现出优异的储存稳定性性能的研究，这是吸入粉末所期望的。
