Lau Michael, Young Paul M, Traini Daniela
Respiratory Technology Group, The Woolcock Institute for Medical Research and Discipline of Pharmacology, Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia.
AAPS PharmSciTech. 2017 Aug;18(6):2248-2259. doi: 10.1208/s12249-016-0708-7. Epub 2017 Jan 9.
The aim of the study was to understand the impact of different concentrations of the additive material, magnesium stearate (MGST), and the active pharmaceutical ingredient (API), respectively, on the physicochemical properties and aerosol performance of comilled formulations for high-dose delivery. Initially, blends of API/lactose with different concentrations of MGST (1-7.5% w/w) were prepared and comilled by the jet-mill apparatus. The optimal concentration of MGST in comilled formulations was investigated, specifically for agglomerate structure and strength, particle size, uniformity of content, surface coverage, and aerosol performance. Secondly, comilled formulations with different API (1-40% w/w) concentrations were prepared and similarly analyzed. Comilled 5% MGST (w/w) formulation resulted in a significant improvement in in vitro aerosol performance due to the reduction in agglomerate size and strength compared to the formulation comilled without MGST. Higher concentrations of MGST (7.5% w/w) led to reduction in aerosol performance likely due to excessive surface coverage of the micronized particles by MGST, which led to failure in uniformity of content and an increase in agglomerate strength and size. Generally, comilled formulations with higher concentrations of API increased the agglomerate strength and size, which subsequently caused a reduction in aerosol performance. High-dose delivery was achieved at API concentration of >20% (w/w). The study provided a platform for the investigation of aerosol performance and physicochemical properties of other API and additive materials in comilled formulations for the emerging field of high-dose delivery by dry powder inhalation.
该研究的目的是分别了解不同浓度的添加剂硬脂酸镁（MGST）和活性药物成分（API）对用于高剂量递送的共研磨制剂的物理化学性质和气溶胶性能的影响。最初，制备了含有不同浓度MGST（1-7.5%w/w）的API/乳糖混合物，并通过气流粉碎机进行共研磨。研究了共研磨制剂中MGST的最佳浓度，特别是对于团聚体结构和强度、粒度、含量均匀性、表面覆盖率和气溶胶性能。其次，制备了具有不同API（1-40%w/w）浓度的共研磨制剂，并进行了类似的分析。与未添加MGST共研磨的制剂相比，共研磨5%MGST（w/w）的制剂由于团聚体尺寸和强度的降低，体外气溶胶性能有显著改善。较高浓度的MGST（7.5%w/w）导致气溶胶性能下降，可能是由于MGST对微粉化颗粒的过度表面覆盖，导致含量均匀性不佳以及团聚体强度和尺寸增加。一般来说，API浓度较高的共研磨制剂会增加团聚体强度和尺寸，进而导致气溶胶性能下降。当API浓度>20%（w/w）时可实现高剂量递送。该研究为通过干粉吸入进行高剂量递送这一新兴领域中其他API和添加剂材料在共研磨制剂中的气溶胶性能和物理化学性质研究提供了一个平台。
