title: Micro-CT analysis of matrix-type drug delivery devices and correlation with protein release behaviour.
abstract: 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.
authors.affiliation: School of Pharmacy and Chemistry, Kingston University, Kingston upon Thames, Surrey KT1 2EE, UK.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Wang
authors.forename: David F
authors.initials: DF
authors.lastname: Wertheim
authors.forename: Allan S
authors.initials: AS
authors.lastname: Jones
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Chang
authors.forename: Allan G A
authors.initials: AG
authors.lastname: Coombes
mesh_terms: D002208:Caproates; D004058:Diffusion; D016503:Drug Delivery Systems; D007783:Lactones; D004364:Pharmaceutical Preparations; D011091:Polyesters; D011506:Proteins; D013535:Suspensions; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D002208:Caproates; D007783:Lactones; D004364:Pharmaceutical Preparations; D011091:Polyesters; D011506:Proteins; D013535:Suspensions; C016240:polycaprolactone; C121056:caprolactone