How does fluid flow influence drug release from drug filled implants?

King, D., McCormick, C. and McGinty, S. (2022) How does fluid flow influence drug release from drug filled implants? Pharmaceutical Research, 39(1), pp. 25-40. (doi: 10.1007/s11095-021-03127-4) (PMID:34997423)

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Drug-filled implants (DFIs) have emerged as an innovative approach to control the delivery of drugs. These devices contain the drug within the structure of the implant itself and avoid the need to include additional drug carrier materials such as a polymers, which are often associated with inflammation and delayed healing/tissue regeneration at the implant site. One common feature of in vitro experiments to generate drug release profiles is stirring or agitation of the release medium. However, the influence of the resulting fluid flow on the rate of drug release from DFIs has yet to be quantified. In this paper we consider two DFIs, which although similar in shape and size, employ different strategies to control the release of drug: a porous pin with pores on the order of μm and a pin drilled with orifices of the order of mm. We develop a multiphysics mathematical model of drug release from these DFIs, subject to fluid flow induced through stirring and show that fluid flow greatly influences the drug release profile for the orifice pin, but that the porous pin drug release profile is relatively insensitive to flow. We demonstrate that drug release from the porous pin may adequately be described through a simplified radial 1D dissolution-diffusion model, while a 3D dissolution-advection-diffusion model is required to describe drug release from the orifice pin. A sensitivity analysis reveals that that the balance of reaction-advection-diffusion in terms of key nondimensional numbers governs the overall drug release. Our findings potentially have important implications in terms of devising the most relevant experimental protocol for quantifying drug release from DFIs.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Mcginty, Dr Sean and King, David
Authors: King, D., McCormick, C., and McGinty, S.
College/School:College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Pharmaceutical Research
ISSN (Online):1573-904X
Published Online:07 January 2022
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Pharmaceutical Research 39(1): 25-40
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190790EPSRC DTG 2014Mary Beth KneafseyEngineering and Physical Sciences Research Council (EPSRC)EP/M506539/1Research and Innovation Services
303232EPSRC Centre for Multiscale soft tissue mechanics with MIT and POLIMI (SofTMech-MP)Xiaoyu LuoEngineering and Physical Sciences Research Council (EPSRC)EP/S030875/1M&S - Mathematics