Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
Center for Medical Research, Medical University of Graz, Graz, Austria.
Eur J Pharm Sci. 2019 Nov 1;139:105065. doi: 10.1016/j.ejps.2019.105065. Epub 2019 Sep 4.
The generation of inhalable sized particles (1-5 μm) usually involves a particle-processing step; most commonly milling but spray drying has shown to be a suitable alternative. Besides particle size, processing may affect other particle properties, like shape and solid-state. For example, spray drying of salbutamol sulphate leads to spherical shaped predominantly amorphous particles whereas jet milling frequently maintains the irregular shape and the crystallinity of the raw material. The aim of the present study was to investigate whether particle properties, especially shape, change the biological action of the inhaled particles as well. Therefore, highly water soluble salbutamol sulphate and poorly water soluble budesonide were compared regarding dissolution, permeation and preferential uptake by epithelial cells compared to macrophages after jet milling and spray drying. For both drugs the spray dried, predominantly amorphous, particles resulted in lower respirable fractions, but higher permeability and cell uptake rates compared to the needle shaped, predominantly crystalline particles. The distinct particle properties did not affect the dissolution behaviour of salbutamol sulphate. In turn for drugs with lower solubility (budesonide), spray dried particles dissolved slower compared to jet milled particles. Preferential uptake by macrophages was higher for spray dried particles, suggesting that processing may improve targeted delivery. The comparison between murine cell lines and human monocyte derived macrophages primary cells showed similar trends in rate and preference of particle uptake.
可吸入大小的颗粒（1-5μm）的生成通常涉及颗粒处理步骤；最常见的是研磨，但喷雾干燥已被证明是一种合适的替代方法。除了颗粒大小之外，处理还可能影响其他颗粒特性，例如形状和固态。例如，硫酸沙丁胺醇喷雾干燥导致球形的主要无定形颗粒，而射流磨通常保持原材料的不规则形状和结晶度。本研究的目的是研究颗粒特性，特别是形状，是否会改变吸入颗粒的生物学作用。因此，与巨噬细胞相比，对高度水溶性的硫酸沙丁胺醇和水溶性差的布地奈德进行了比较，研究了它们在射流磨和喷雾干燥后的溶解、渗透和上皮细胞优先摄取情况。对于这两种药物，喷雾干燥的、主要无定形的颗粒导致更低的可吸入分数，但与针状的、主要结晶的颗粒相比，具有更高的渗透率和细胞摄取率。不同的颗粒特性并不影响硫酸沙丁胺醇的溶解行为。对于溶解度较低的药物（布地奈德），喷雾干燥的颗粒溶解速度较慢，而射流磨的颗粒溶解速度较快。喷雾干燥的颗粒被巨噬细胞优先摄取，这表明处理可能会改善靶向输送。鼠类细胞系和人单核细胞衍生的巨噬细胞原代细胞之间的比较显示出颗粒摄取的速率和偏好性相似的趋势。
