| Dry powder inhalants (DPIs), an attractive alternative method of drug delivery, are among the many technologically significant systems in which control of the adhesion of particles to solid surfaces is an important factor in their performance. A typical DPI system consists of micronized drug particles, carrier particles (typically lactose), a gelatin capsule, and an inhalation device. Development of DPI formulations with high reproducibility of the respirable mass of drug is necessary to ensure accurate drug delivery with each usage of the inhaler. Particle-capsule and particle-particle adhesion processes affect the characteristics of the aerosol formed and, thus, the respirable mass of the drug. The adhesion processes are dependent on the physicochemical properties of the particle and capsule surfaces, as well as environmental conditions.; The primary focus of this research was to investigate the adhesion of lactose carrier particles to gelatin surfaces in an effort to improve the understanding of adhesion phenomena important to DPI technology. This was achieved by directly measuring the adhesion of individual lactose particles to gelatin capsule surfaces using the colloidal probe technique of scanning probe microscopy (SPM). The relevance of SPM adhesion measurements using individual particles was verified by comparing these microscopic adhesion measurements with macroscopic retention studies. Several other SPM techniques such as height, friction and phase imaging were used to characterize the physicochemical properties of commercial gelatin capsule surfaces. Furthermore, this combination of SPM imaging techniques, along with elasticity and adhesion mapping, was used to correlate the adhesion of lactose particles with areas of distinct surface physicochemical properties on gelatin capsules. Extraneous surface contamination as a key factor contributing to physicochemical heterogeneity on individual gelatin capsules, as well as multiple capsules from the same batch, from different batches and from different manufacturers, was investigated by the surface analytical techniques of ESCA and TOF-SIMS. From the characterization of the gelatin capsule surfaces and the correlation of the particle adhesion with distinct areas on capsule surfaces, a more fundamental understanding of the adhesion processes was gained, which, in turn, offers opportunities for improved control of the respirable mass in DPI systems. Attempts to develop a model system to investigate the intrinsic adhesion of lactose particles to gelatin surfaces are also presented and discussed. |
