Enhancing the performance of dry powder inhalates with any inhalable active pharmaceutical ingredient by using spray dried mannitol carrier particles with tailored surface roughness

通过使用具有定制表面粗糙度的喷雾干燥甘露醇载体颗粒，增强任何可吸入活性药物成分的干粉吸入剂的性能

• 批准号: 122634570
• 负责人: Professorin Dr. Regina Scherließ, since 10/2014
• 金额: --
• 依托单位: Daiichi Sankyo Europe GmbH
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/122634570?language=en
• 关键词: Enhancing; performance; dry; powder; inhalates

The aim of the current proposal is to tailor the quality attributes – especially the respirable fraction - of powders for inhalation consisting of a carrier and any active pharmaceutical ingredient (API) suitable for inhalation therapy. As the respirable fraction is dependent on interparticle forces between the API and the carrier and as the interparticle forces in turn rely on the surface topography of the carrier, this may be achieved by modifying the surface topography of mannitol carrier particles via spray drying. The focus of the first and the second funding period was on providing of mannitol carrier particles with tailor-made surface topography. The results of these studies will be used in the upcoming third funding period to combine the surface modified carrier particles with any inhalable API in order to optimize the respirable fraction, which is besides carrier surface topography dependent on the properties of the API as well. Already during the second funding period salbutamol sulphate particles of various sizes and shapes were prepared by milling and spray drying in order to evaluate the influence of geometric factors on the respirable fraction. In the upcoming third funding period API with various physico-chemical properties will be included. The aim of these studies is to check whether there is a correlation between the API properties and the respirable fraction as well as the development of a rational approach of selecting the appropriate carrier for any inhalable API. Using this platform it will become possible to develop dry powder inhalates for any new chemical entity on a scientific basis, which may reduce time and costs of the development process. Additionally, a second part of this proposal is dedicated to the simulation of mannitol particle formation within the spray drying process in order to enhance the insight into the particle formation mechanism of mannitol and the process understanding. A multi phase approach is used to simulate the spray drying process depending on substance specific parameters (solubility, viscosity, etc.) as well as on process parameters (humidity, temperature, etc.).

当前提案的目的是定制由载体和任何适用于吸入治疗的活性药物成分（API）组成的吸入粉末的质量属性-特别是可吸入部分。由于可吸入部分取决于原料药和载体之间的颗粒间力，而颗粒间力又依赖于载体的表面形貌，这可以通过喷雾干燥来改变甘露醇载体颗粒的表面形貌来实现。第一和第二个资助期的重点是提供具有定制表面形貌的甘露醇载体颗粒。这些研究的结果将用于即将到来的第三个资助期，将表面改性的载体颗粒与任何可吸入的原料药结合起来，以优化可吸入部分，除了载体表面形貌取决于原料药的性质之外。在第二个资助期内，已经通过研磨和喷雾干燥制备了各种大小和形状的硫酸沙丁胺醇颗粒，以评估几何因素对可吸入部分的影响。在即将到来的第三个资助期内，将包括具有各种物理化学性质的API。这些研究的目的是为了检查原料药的性质与可吸入组分之间是否存在相关性，以及为任何可吸入原料药选择合适载体的合理方法。使用该平台，将有可能在科学的基础上为任何新的化学实体开发干粉吸入剂，这可能会减少开发过程的时间和成本。此外，本提案的第二部分致力于模拟甘露醇颗粒在喷雾干燥过程中的形成，以增强对甘露醇颗粒形成机制和过程理解的洞察。采用多相方法根据物质特定参数（溶解度、粘度等）以及工艺参数（湿度、温度等）来模拟喷雾干燥过程。