Stankovic-Brandl Milica, Radivojev Snezana, Sailer Pia, Penz Franz-Karl, Paudel Amrit
Research Center Pharmaceutical Engineering, Inffeldgasse 13, Graz, 8010, Austria.
Research Center Pharmaceutical Engineering, Inffeldgasse 13, Graz, 8010, Austria; Center for Medical Research, Stiftingtalstrasse 24, Graz, 8010, Austria.
Int J Pharm. 2022 Dec 15;629:122359. doi: 10.1016/j.ijpharm.2022.122359. Epub 2022 Nov 1.
Dry powder inhalers (DPIs) are regularly used to treat respiratory diseases. Adding extrinsic fine excipient particles to the blend of active pharmaceutical ingredient (API) and carrier is an established strategy to improve aerosolization efficiency during pulmonary drug delivery. Different amounts and grades of lactose fines may, however, compromise the flowability and downstream processing of the material. Further, given the particle size of the inhaled fine particles (<5.5 µm), also deposition of lactose fines to different lung regions following inhalation cannot be excluded. This study aimed to investigate the impact of commercially available extrinsic lactose fine materials produced using different milling parameters, on physicochemical properties and aerosolization performance of ternary blends, as a factor of time and storage conditions. Further, for the first time, it was attempted to elucidate the effect that the amount of present fines has on the dissolution of the model API from the ternary blends exposed to different storage conditions. We showed that rheological behavior was impacted when a higher amount of fines was present, and this effect was further enhanced by storage at high relative humidity. The aerosolization efficiency was vastly improved with increasing content of fines. Still, initial data indicated that the dissolution of the poorly soluble API was retarded when more fines were present in blends.
干粉吸入器（DPIs）常用于治疗呼吸系统疾病。在活性药物成分（API）与载体的混合物中添加外部细赋形剂颗粒是一种既定的策略，可提高肺部给药期间的雾化效率。然而，不同数量和等级的乳糖细粉可能会损害材料的流动性和下游加工性能。此外，考虑到吸入细颗粒的粒径（<5.5 µm），吸入后乳糖细粉在不同肺区域的沉积也不能排除。本研究旨在调查使用不同研磨参数生产的市售外部乳糖细粉材料对三元混合物的物理化学性质和雾化性能的影响，作为时间和储存条件的一个因素。此外，首次尝试阐明细粉含量对暴露于不同储存条件下的三元混合物中模型API溶解的影响。我们发现，当细粉含量较高时，流变行为会受到影响，并且在高相对湿度下储存会进一步增强这种影响。随着细粉含量的增加，雾化效率大幅提高。不过，初步数据表明，当混合物中细粉含量更多时，难溶性API的溶解会受到阻碍。
