Jain, A., King, D. , Pontrelli, G. and Mcginty, S. (2023) Controlling release from encapsulated drug-loaded devices: insights from modeling the dissolution front propagation. Journal of Controlled Release, 360, pp. 225-235. (doi: 10.1016/j.jconrel.2023.06.019) (PMID:37328006)
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Abstract
Dissolution of drug from its solid form to a dissolved form is an important consideration in the design and optimization of drug delivery devices, particularly owing to the abundance of emerging compounds that are extremely poorly soluble. When the solid dosage form is encapsulated, for example by the porous walls of an implant, the impact of the encapsulant drug transport properties is a further confounding issue. In such a case, dissolution and diffusion work in tandem to control the release of drug. However, the interplay between these two competing processes in the context of drug delivery is not as well understood as it is for other mass transfer problems, particularly for practical controlled-release considerations such as an encapsulant layer around the drug delivery device. To address this gap, this work presents a mathematical model that describes controlled release from a drug-loaded device surrounded by a passive porous layer. A solution for the drug concentration distribution is derived using the method of eigenfunction expansion. The model is able to track the dissolution front propagation, and predict the drug release curve during the dissolution process. The utility of the model is demonstrated through comparison against experimental data representing drug release from a cylindrical drug-loaded orthopedic fixation pin, where the model is shown to capture the data very well. Analysis presented here reveals how the various geometrical and physicochemical parameters influence drug dissolution and, ultimately, the drug release profile. It is found that the non-dimensional initial concentration plays a key role in determining whether the problem is diffusion-limited or dissolution-limited, whereas the nature of the problem is largely independent of other parameters including diffusion coefficient and encapsulant thickness. We expect the model will prove to be a useful tool for those designing encapsulated drug delivery devices, in terms of optimizing the design of the device to achieve a desired drug release profile.
| Item Type: | Articles |
|---|---|
| Additional Information: | David King would like to gratefully acknowledge the funding provided by EPSRC (grant number EP/M506539/1). Sean McGinty acknowledges funding provided by EPSRC (grant number EP/S030875/1). Giuseppe Pontrelli acknowledges funding from the European Research Council under the European Unions Horizon 2020 Framework Programme (No. FP/2014–2020)/ ERC Grant Agreement No. 739964 (COPMAT). |
| Keywords: | Dissolution, diffusion, drug delivery devices, drug release profile, dissolution front propagation. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Mcginty, Dr Sean and Pontrelli, Dr Giuseppe and King, Dr David |
| Creator Roles: | Mcginty, S.Conceptualization, Methodology, Formal analysis, Validation, Writing – original draft, Writing – review and editing |
| Authors: | Jain, A., King, D., Pontrelli, G., and Mcginty, S. |
| College/School: | College of Science and Engineering > School of Engineering > Biomedical Engineering College of Science and Engineering > School of Mathematics and Statistics > Mathematics |
| Journal Name: | Journal of Controlled Release |
| Publisher: | Elsevier |
| ISSN: | 0168-3659 |
| ISSN (Online): | 1873-4995 |
| Published Online: | 26 June 2023 |
| Copyright Holders: | Copyright © 2023 The Authors |
| First Published: | First published in Journal of Controlled Release 360:225-235 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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