Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia.
Drug Dev Ind Pharm. 2012 Dec;38(12):1504-11. doi: 10.3109/03639045.2012.654793. Epub 2012 Feb 16.
To evaluate physicochemical properties of two micronized drugs, salbutamol sulfate (SS) and beclomethasone dipropionate (BDP) prepared as dry powder inhalation physical blends.
Five different blends of SS:BDP ratios of 0:100, 25:75, 50:50, 75:25, and 100:0 (w/w) were prepared. Aerosolization performance was evaluated using a multistage impinger and a Rotahaler® device.
The median SS particle diameter was larger than BDP (4.33 ± 0.37 µm compared to 2.99 ± 0.15 µm, respectively). The SS appeared to have a ribbon-like morphology, while BDP particles had plate-like shape with higher cohesion than SS. This was reflected in the aerosolization performance of the two drugs alone, where SS had a significantly higher fine particle fraction (FPF) than BDP (12.3%, 3.1% and 2.9%, 0.2%, respectively). The study of cohesion versus adhesion for a series of SS and BDP probes on SS and BDP substrates suggested both to be moderately adhesive, verified using scanning Raman microscopy, where a physical association between the two was observed. A plot of loaded versus emitted dose indicated that powder bed fluidization was significantly different when the drugs were tested individually. Furthermore, the FPF of the two drugs from the binary blends, at all three ratios, were similar.
Such observations indicate that when these two drugs are formulated as a binary system, the resulting powder structure is altered and the aerosolization performance of each drug is not reflective of the individual drug performance. Such factors could have important implications and should be considered when developing combination dry powder inhalation systems.
评估两种微米化药物沙丁胺醇硫酸盐（SS）和丙酸倍氯米松（BDP）作为干粉吸入物理混合物的物理化学性质。
制备了 SS:BDP 比为 0:100、25:75、50:50、75:25 和 100:0（w/w）的五种不同 SS:BDP 混合物。使用多阶段撞击器和 Rotahaler®装置评估雾化性能。
SS 的中值粒径大于 BDP（分别为 4.33±0.37 µm 和 2.99±0.15 µm）。SS 似乎具有带状形态，而 BDP 颗粒具有板状形状，与 SS 相比具有更高的内聚性。这反映在两种药物单独的雾化性能上，SS 的细颗粒分数（FPF）明显高于 BDP（分别为 12.3%、3.1%和 2.9%、0.2%）。对一系列 SS 和 BDP 探针在 SS 和 BDP 基质上的内聚性与粘附性的研究表明，两者均具有中等的粘附性，使用扫描拉曼显微镜得到了验证，其中观察到两种药物之间存在物理结合。加载量与发射量的关系表明，当单独测试药物时，粉末床流化有明显的差异。此外，两种药物在所有三个比例的二元混合物中的 FPF 相似。
这些观察结果表明，当这两种药物被配方制成二元体系时，所得粉末结构发生改变，每种药物的雾化性能不再反映单个药物的性能。这些因素可能具有重要意义，在开发组合干粉吸入系统时应予以考虑。
