What Could Be Learned From Glass Beads As Model Carrier System?
Niklas Renner1 Hartwig Steckel, Nora Urbanetz & Regina Scherließ1
1Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, 24118 Kiel, Germany
2Deva Holding A.S., Istanbul, Turkey 3Daiichi Sankyo, Pfaffenhofen, Germany
Glass beads (GBs) represent an innovative model carrier system to investigate the complex mechanisms that govern drug detachment and deagglomeration of carrier-based formulations. Therefore, the surface of GBs was modified via different methods to either alter surface chemistry or topography. The former was done through silanisation of the GB surface and determined via contact angle measurements and inverse gas chromatography. The latter was achieved by incubation with hydrofluoric acid and/or ball-milling with tungsten carbide. This was investigated utilising scanning electron and atomic force microscopy. Two APIs with differing properties, namely budesonide and formoterol fumarate, were spray-dried to obtain particles in the suitable size range for inhalation and a uniform shape. Aerodynamic performance of the different API-carrier blends was subsequently investigated by impaction analysis. It could be demonstrated that surface chemistry of the carrier was more important for a hydrophobic drug (budesonide) while their impact on aerodynamic performance was limited when using more hydrophilic APIs. On the contrary, the alteration of carrier surface topography on micro- and/or nano-scale showed the same trends for both APIs. Micro-scale indentations proved to be able to shelter drug particles from drag and lift forces created by the Cyclohaler®. Nano-scale roughness reduced the contact area between carrier and API and therefore facilitated drug detachment which could be confirmed by reduced adhesion forces. These trends also applied to drugs in micronised quality. As a consequence, surface topography should be adjusted in formulation development to nano-scale roughness regardless of the API properties to obtain enhanced aerodynamic performance.