Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, 24118 Kiel, Germany.
Deva Holding A.S., Istanbul, Turkey.
Int J Pharm. 2017 Feb 25;518(1-2):20-28. doi: 10.1016/j.ijpharm.2016.12.052. Epub 2016 Dec 23.
The present study investigates the effect of different carrier surface modifications on the aerosolisation performance and on the effective carrier payload of interactive blends for inhalation. Two different active pharmaceutical ingredients (APIs) were used: Formoterol fumarate dihydrate (FF) and budesonide (BUD). Blends were prepared with glass beads as model carriers which have been subjected to mechanical surface modifications in order to introduce surface roughness via treatment with hydrofluoric acid (HF) and/or milling with tungsten carbide (TC). As far as effective carrier payload, in this study expressed as true surface coverage (TSC), is concerned, surface modification had varying effects on blends containing BUD or FF. Aerodynamic characterisation in vitro showed a significant decrease in respirable fraction for glass beads treated with HF (40.2-50.1%), due to the presence of clefts and cavities, where drug particles were sheltered during inhalation. In contrast, grinding with TC leads to surface roughness on a nano scale, ultimately increasing aerodynamic performance up to 20.0-38.1%. These findings are true for both APIs, regardless of their chemical properties.
本研究考察了不同载体表面修饰对吸入用互动混合物的气溶胶化性能和有效载体载药量的影响。使用了两种不同的活性药物成分（APIs）：富马酸福莫特罗二水合物（FF）和布地奈德（BUD）。将玻璃珠作为模型载体进行机械表面修饰，以通过氢氟酸（HF）处理和/或碳化钨（TC）研磨来引入表面粗糙度，从而制备混合物。就有效载体载药量而言，在本研究中表示为真实表面覆盖率（TSC），表面修饰对含有 BUD 或 FF 的混合物有不同的影响。体外空气动力学特性表明，经 HF 处理的玻璃珠的可吸入分数显著降低（40.2-50.1%），这是由于存在裂缝和空腔，药物颗粒在吸入过程中被保护在其中。相比之下，用 TC 研磨会导致纳米级的表面粗糙度，最终使空气动力学性能提高 20.0-38.1%。这些发现对两种 API 都是正确的，无论其化学性质如何。
