Pinto Joana T, Radivojev Snezana, Zellnitz Sarah, Roblegg Eva, Paudel Amrit
Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria; Institute of Pharmaceutical Sciences, Pharmaceutical Technology and Biopharmacy, University of Graz, Universitätsplatz 1, 8010 Graz, Austria.
Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria.
Int J Pharm. 2017 Aug 7;528(1-2):416-428. doi: 10.1016/j.ijpharm.2017.06.027. Epub 2017 Jun 12.
As pulmonary drug delivery is extended from low doses to high doses, physicochemical characteristics of the active pharmaceutical ingredient gain importance in the development of dry powder inhalers. Therefore, the present work aims to understand the impact of distinct engineering techniques on the process induced physicochemical characteristics of salbutamol sulphate particles over time. The particle engineering techniques chosen were jet-milling and spray-drying, two well used processes in the production of predominately crystalline and amorphous inhalable particles, respectively. Fourier transform infrared spectroscopy, modulated differential scanning calorimetry, particle size distribution and tensiometry experiments were used to characterise the engineered powders immediately, 7, 14 and 21 days after production. The rugged spherical amorphous particles (3.75±0.08μm) obtained via spray-drying showed that they were capable of forming strong agglomerates (5.01±0.22μm) through "amorphous bridging". On the other hand, jet-milling produced smaller (2.06±0.08μm), crystalline, irregular shaped particles with a very large surface area (11.04±0.10m/g) that, over time, formed looser particle aggregates of decreasing size (3.76±0.10μm). Temporal evolution of the properties of spray-dried and jet milled particles showed a notable influence on the efficiency of blending with a model carrier at 0, 7 and 21 days (e.g. relative standard deviation of drug content of 11.3, 7.0 and 21.6%, respectively).
随着肺部药物递送从低剂量扩展到高剂量，活性药物成分的物理化学特性在干粉吸入器的开发中变得愈发重要。因此，本研究旨在了解不同的工程技术对硫酸沙丁胺醇颗粒随时间变化的过程诱导物理化学特性的影响。所选用的颗粒工程技术分别是气流粉碎和喷雾干燥，这是两种在生产主要为结晶态和无定形态可吸入颗粒时常用的工艺。采用傅里叶变换红外光谱、调制差示扫描量热法、粒度分布和表面张力测定实验，对生产后即刻、7天、14天和21天的工程化粉末进行表征。通过喷雾干燥获得的坚固球形无定形颗粒（3.75±0.08μm）表明，它们能够通过“无定形桥连”形成强团聚体（5.01±0.22μm）。另一方面，气流粉碎产生的颗粒较小（2.06±0.08μm）、呈结晶态、形状不规则且表面积非常大（11.04±0.10m²/g）,随着时间的推移，会形成尺寸逐渐减小的较松散颗粒聚集体（3.76±0.10μm）。喷雾干燥颗粒和气流粉碎颗粒性质的时间演变对在0天、7天和21天与模型载体混合的效率有显著影响（例如，药物含量的相对标准偏差分别为11.3%、7.0%和21.6%）。
