Differences in physical chemistry and dissolution rate of solid particle aerosols from solution pressurised inhalers
Differences in physical chemistry and dissolution rate of solid particle aerosols from solution pressurised inhalers
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DOI：
10.1016/j.ijpharm.2014.01.033
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发表时间：
2014-04-25
影响因子：
5.8
通讯作者：
Forbes, Ben
中科院分区：
文献类型：
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作者：
Buttini, Francesca;Miozzi, Michele;Forbes, Ben
溶液组成改变了由加压计量吸入器(PMDI)释放的液滴形成二氯米松(BDP)颗粒的动力学。吸入器溶液的不同会导致不同的固体颗粒物理化学，这一假设是使用一套互补量热技术进行测试的。来自商用HFA-pMDI的BDP-乙醇溶液的雾化产生了空气动力学上等效的固体颗粒气雾剂。然而，通过差示扫描量热仪(DSC)、热重分析(TGA)和热台显微镜(HSM)检测到了颗粒物理化学(形态和溶剂/笼合物的形成)的差异。将配方中的乙醇含量从8%提高到12%(w/w)，可以延缓推进剂的蒸发，减缓液滴表面粘度的增加，从而增加颗粒干燥的可能性，使颗粒表面光滑。与8%(w/w)乙醇配方衍生颗粒(86%在120分钟内溶解)相比，12%(w/w)乙醇配方衍生颗粒(63%溶解超过120 mm)的BDP溶解速度降低。在吸入液中加入0.01%(w/w)富马酸福莫特罗或1.3%(w/w)甘油，可使BDP在120 mm中的溶出度分别降至34%和16%。这些数据提供了证据，表明来自明显相似的吸入器产品的治疗性气雾剂，包括那些具有类似空气动力学性能的产品，在肺部沉积后可能表现不同。(C)2014爱思唯尔B.V.保留所有权利。
Solution composition alters the dynamics of beclomethasone diproprionate (BDP) particle formation from droplets emitted by pressurised metered dose inhalers (pMDIs). The hypothesis that differences in inhaler solutions result in different solid particle physical chemistry was tested using a suite of complementary calorimetric techniques. The atomisation of BDP-ethanol solutions from commercial HFA-pMDI produced aerodynamically-equivalent solid particle aerosols. However, differences in particle physico-chemistry (morphology and solvate/clathrate formation) were detected by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and supported by hot stage microscopy (HSM). Increasing the ethanol content of the formulation from 8 to 12% (w/w), which retards the evaporation of propellant and slows the increase in droplet surface viscosity, enhanced the likelihood of particles drying with a smooth surface. The dissolution rate of BDP from the 12% (w/w) ethanol formulation-derived particles (63% dissolved over 120 mm) was reduced compared to the 8% (w/w) ethanol formulation-derived particles (86% dissolved over 120 min). The addition of 0.01% (w/w) formoterol fumarate or 1.3% (w/w) glycerol to the inhaler solution modified the particles and reduced the BDP dissolution rate further to 34% and 16% dissolved in 120 mm, respectively. These data provide evidence that therapeutic aerosols from apparently similar inhaler products, including those with similar aerodynamic performance, may behave non-equivalently after deposition in the lungs. (C) 2014 Elsevier B.V. All rights reserved.