Modeling the sustained release of PLGA-based drug delivery systems with a physically-based model and pore space characterization
Date
2022
Authors
Shi, Xutao
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Sustained release systems have demonstrated benefits in the field of drug delivery owing to their improved therapeutic efficacy, high patient compliance, bioactivity, and biocompatibility. With a number of physico-chemical processes in effect, well-controlled long-term release behavior from these systems is required to maintain their effectiveness and reliability, giving rise to extensive experimental studies that further add to the cost of product development. In this study, we present an improved mechanistic sustained release model by incorporating a description of hydrolytic polymer degradation kinetics, which is validated against an extensive data set of drug release, water uptake, and polymer degradation from an in vitro study of a drug-surrogate-embedded PLGA system. Reasonable agreement between model predictions and experimental drug release profiles was observed while discrepancies for certain formulations lead to a hypothesized correlation between first-phase rapid release and internal pore formation. In light of this, characterization of the pore space network for nine PLGA rod formulations was performed with the use of X-ray computed tomography and image segmentation. As a result, correlations of varying significance between the amount of first-phase release and geometric parameters were found and it was shown that the mean sphericity of the pore space network may be negatively correlated with the first-phase release, although the similar range in the variances of the mean sphericity warrants a more in-depth statistical study to determine the value and significance of this correlation. In addition, the evolution of the pore size distribution was captured with the use of a properly formulated population balance model. Good agreement between model predictions and experimental physical moments of the pore space network was found and further demonstrated with the reconstructed number distributions of the individual pore volume, highlighting the potential of the population balance model in tracking pore space evolution during the release timeline.
Description
Keywords
Drug delivery systems, Pore space characterization, Sustained release systems