School of Life Sciences, University of Bradford, BD7 1DP, UK.
Int J Pharm. 2011 Aug 30;415(1-2):62-72. doi: 10.1016/j.ijpharm.2011.05.043. Epub 2011 Jun 12.
Salbutamol sulphate (SS) used in dry powder inhalers requires drug particles in the respirable size range of 1-5 μm to achieve a suitable therapeutic effect. The aim of this study was therefore to determine strategies for controlling drug substance characteristics pre and post-crystallisation to facilitate the production of micronised SS with desirable particle attributes for optimal delivery as an inhaled aerosol. SS batches were crystallised using an antisolvent method to produce a range of crystal morphologies. Air jet milling was then used to reduce the size of crystallised SS particles. Starting materials and micronised batches of SS were characterised in the solid state using a range of techniques with subsequent assessment of aerosol properties. Assessment of the aerodynamic characteristics of micronised SS delivered by DPI (without any carrier) indicated that fine particle fraction and emitted dose as a percentage of the total recovered dose were dependent on the quality attributes of the micronised SS, which were directly linked to the degree of imperfections and the morphology of the crystalline feedstock used in micronisation. Aerosolization performance of micronised SS can be optimised by manipulation of feedstock characteristics through crystal engineering and through definition of optimal processing conditions for micronisation.
硫酸沙丁胺醇（SS）在干粉吸入器中使用时，需要药物颗粒在 1-5μm 的可呼吸范围内，以达到适当的治疗效果。因此，本研究的目的是确定在结晶前后控制药物特性的策略，以方便生产具有理想颗粒特性的微米级 SS，从而将其作为吸入式气溶胶最佳传递。使用抗溶剂法使 SS 批料结晶，以产生一系列晶体形态。然后使用空气喷射磨将结晶 SS 颗粒的尺寸减小。使用一系列技术对起始材料和微米化的 SS 批次进行固态特性表征，随后对气溶胶特性进行评估。对 DPI （不使用任何载体）输送的微米化 SS 的空气动力学特性进行评估表明，细颗粒分数和作为总回收剂量的百分比的释放剂量取决于微米化 SS 的质量特性，这直接与结晶原料的不完美程度和晶体形态有关用于微米化。通过通过晶体工程操纵原料特性并通过定义微米化的最佳加工条件，可以优化微米化 SS 的气溶胶化性能。
