Micro-CT analysis of matrix-type drug delivery devices and correlation with protein release behaviour.

摘要

A series of matrix-type drug delivery devices comprising a continuous phase of microporous poly(epsilon-caprolactone) (PCL) and a dispersed phase of protein particles (gelatin) with defined size ranges (45-90, 90-125 and 125-250 microm) were produced by rapidly cooling suspensions in dry ice followed by solvent extraction from the hardened material. High protein loadings (38-44%, w/w) were achieved and highly efficient protein release (90% of the initial load) was obtained over time periods of 3-11 days depending on particle loading and size range. The duration of protein release was extended from 3 to 11 days by reducing the protein load. Quantitative analysis of Micro-CT images identified a three to four times increase in the population of sub-40 microm pores in those matrices which gave rise to accelerated protein release in 24 h (40% rising to 80%) and reduced duration of protein release (11-3 days). Formation of a high density of channels and fissures (connects) between the particles is indicated, which facilitate fluid ingress and diffusion of solubilised protein molecules. Micro-CT analysis also confirmed the uniformity of particle distribution in the matrices and provided measurements of macroporosity within 5-30% of the theoretical value for materials displaying irregular shaped macropores larger than 90 microm. These findings demonstrate the utility of Micro-CT for optimising the formulation and performance of matrix-type delivery devices for macromolecular entities.