Allan Coombes
The University of Queensland, Pharmacy Australia Centre of Excellence, Woolloongabba, QLD 4102, Australia

Abstract:

Micro-computed tomography (micro-CT) has not to date been fully exploited in the area of controlled drug delivery despite its capability for providing detailed, 3-D images of material morphology. Micro-CT was used to characterize the internal structure of polycaprolactone (PCL) matrix-type devices incorporating gelatin particles (Mw 20-25kDa) as a model of protein therapeutics or pore forming excipients. Micro-CT images confirmed that gelatin particles were uniformly dispersed throughout the PCL phase and that the resulting efficient delivery of protein (95-100%) involved transport from the matrix core. Quantitative analysis of micro-CT images provided values for matrix macroporosity, which were within 15% of the theoretical value. Total release of protein occurred in 9 days (PBS, 37°C) from matrices containing a high protein load (44% w/w) and was independent of particle size. Measurements of equivalent pore diameter and frequency distribution using image analysis identified a large population of sub-40 micron pores in each material, indicative of a high density of connecting channels or fissures between particles which facilitates protein transport through the matrix. Micro-CT image analysis presents major opportunities for exploring the relationships between delivery device formulation, structure and performance which should lead to improvements in administration of small molecule and macromolecular therapeutics.