(696g) Comparing Physically and Chemically Modified Glass Beads As Model Carrier Particles in Dry Powder Inhalers

Interparticle interactions play a crucial role in carrier-based dry powder inhalers (DPIs). It is important, that they are on the one hand high enough that uniform dosing is possible and on the other hand low enough that drug detachment from the carrier during inhalation is guaranteed. Interparticle interactions are affected by a multitude of factors of which particle surface properties is the major factor studied. Different attempts have been made to modify the surface properties of commonly used carriers like lactose or mannitol. However in most of these cases, several other properties impacting interparticle interactions like particle size or shape of the carrier particles were altered besides the surface properties. For example, Maas et al. recently reported that the carrier surface modification of mannitol by spray drying at different conditions [1] . The surface manipulation of particles also often alters the shape of the particles which would possibly have an impact on the final product properties. To prevent the possible shape alteration accompanying the particle surface modifications, the present study aims to use glass beads as the model carriers. Glass beads possess ideal geometry and are available in different sizes. More importantly, they allow various prospects of chemical and physical surface modification, without affecting other factors also influencing interparticle forces.

Physical surface modification was performed in a ball mill (Ball Mill S2, Retsch, Haan, Germany) using quartz and tungsten carbide powders as grinding materials and different grinding times. As a result glass beads (SiLibeads® Glass Beads Type S, Sigmund Linder GmbH, Warmensteinach, Germany) with different shades of roughness have been generated [2]. The result of preparation and characterization as well as the impact of physical surface processing on the mixing behaviour of the modified glass beads with a model API was presented at the AIChE Meeting, 2013. In view of the possible impact of surface chemistry of glass beads on interparticle interactions besides surface roughness,  the present work focuses on the preparation of chemically modified glass beads and the comparison of chemically and physically modified glass beads as model carriers in DPIs. By chemical surface treatment with different silanes (3,3,3-Trifluoropropyltrimethoxysilane (FPTS), Trimethylchlorosilane (TMCS) and Triphenylchlorosilane (TPCS)) and, glass beads with hydrophobic surfaces were  generated.

Adhesive mixtures of chemically as well as physically modified glass beads and spray dried salbutamol sulphate (Selectchemie, Zuerich, Switzerland), as model API, were prepared in a tumble blender.

Next, in vitro lung deposition experiments were performed with a next generation impactor (NGI) and the fine particle fraction (FPF) was calculated. The FPF provides an estimate of the percentage of API particles that are detached from the carrier during inhalation and thereby able to reach the deep lung. Therefore, the FPF values are often considered as the main parameter describing the performance of a DPI system. Thus, the FPF values were chosen to compare the differently modified carriers in the present study.

The evaluation of the FPF showed that physically modified glass beads show an increased FPF when compared to untreated and chemically modified glass beads. Moreover, the results showed the increase in FPF with increasing surface roughness. For chemically modified glass beads, the FPF decreases with increasing surface hydrophobicity.

The obtained data are highly useful to improve the understanding of carrier surface properties on the FPF and thus the performance of DPIs.

Acknowledgements

The authors wish to thank the DFG for financial support within the priority program “Particles in contact SPP 1486”

References

[1]      S.G. Maas, G. Schaldach, E.M. Littringer, A. Mescher, U.J. Griesser, D.E. Braun, et al., The impact of spray drying outlet temperature on the particle morphology of mannitol, Powder Technol. 213 (2011) 27–35. doi:10.1016/j.powtec.2011.06.024.

[2]      S. Zellnitz, J.D. Redlinger-Pohn, M. Kappl, H. Schroettner, N.A. Urbanetz, Preparation and characterization of physically modified glass beads used as model carriers in dry powder inhalers., Int. J. Pharm. 447 (2013) 132–8. doi:10.1016/j.ijpharm.2013.02.044.