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

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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.).