Brodka-Pfeiffer Katharina, Langguth Peter, Grass Peter, Häusler Heribert
Boehringer Ingelheim Pharma KG, Ingelheim am Rhein, Germany.
Eur J Pharm Biopharm. 2003 Nov;56(3):393-400. doi: 10.1016/s0939-6411(03)00134-6.
In order to obtain the optimal particle size distribution for pharmaceutical powders in dry powder inhalers the particles have to be micronised. In most cases the process of micronisation is connected with a high input of energy which induces disorder and defects on the surface of the drug particles and as a result changes in the crystallinity. Consequently, changes in the physical stability of the powders may occur. To investigate changes on the physical stability of the powder, different analytical methods are used in the present investigation: laser diffraction, Differential Scanning Calorimetry (DSC), isothermal microcalorimetry and DVS-method.Air-jet-milling is one of the most frequently used techniques in the pharmaceutical industry, in order to obtain particles of respirable size. In the treatise described here the influence of the critical parameters of the process, i.e. feed pressure, grind pressure and feed rate is assessed for salbutamol sulphate. The grind pressure is of utmost importance with respect to particle size distribution and the physical powder stability. For salbutamol sulphate, ground with a MC Jetmill 50, a grind pressure of 6 bar has been found optimal. Pressures below 6 bar are not sufficient to produce the required reduction in particle size. The feed pressure and rate have negligible influence on the powder quality. Furthermore, the micronisation process is optimised to achieve respirable particles while minimising the amorphous content. A correlation between mechanical activation and the amount of the amorphous regions is showed clearly.Air-jet-milling has been compared to ball milling in this investigation. In pilot tests ball milling was not suitable to achieve the needed particle size distribution, however, it generates a specific quantity of amorphous material. With the help of specific amorphous regions in the powder, the sensitivity of the used methods for salbutamol sulphate can be examined.
为了获得干粉吸入器中药物粉末的最佳粒度分布，必须对颗粒进行微粉化处理。在大多数情况下，微粉化过程需要大量的能量输入，这会在药物颗粒表面引发无序和缺陷，从而导致结晶度发生变化。因此，粉末的物理稳定性可能会改变。为了研究粉末物理稳定性的变化，本研究采用了不同的分析方法：激光衍射、差示扫描量热法（DSC）、等温微量热法和动态蒸汽吸附法（DVS法）。气流粉碎是制药行业最常用的技术之一，目的是获得可吸入尺寸的颗粒。在本文所述的论文中，评估了硫酸沙丁胺醇气流粉碎过程中关键参数（即进料压力、研磨压力和进料速率）的影响。研磨压力对于粒度分布和粉末的物理稳定性至关重要。对于使用MC Jetmill 50进行研磨的硫酸沙丁胺醇，已发现6巴的研磨压力是最佳的。低于6巴的压力不足以使颗粒尺寸减小到所需程度。进料压力和进料速率对粉末质量的影响可忽略不计。此外，对微粉化过程进行了优化，以获得可吸入颗粒，同时尽量减少无定形成分的含量。机械活化与无定形区域数量之间的相关性得到了明确体现。在本研究中，将气流粉碎与球磨进行了比较。在中试试验中，球磨不适合获得所需的粒度分布，然而，它会产生一定量的无定形材料。借助粉末中特定的无定形区域，可以检验所使用的硫酸沙丁胺醇分析方法的灵敏度。
