Reservoir-Style Polymeric Drug Delivery Systems: Empirical and Predictive Models for Implant Design
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Published:2022-10-03
Issue:10
Volume:15
Page:1226
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ISSN:1424-8247
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Container-title:Pharmaceuticals
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language:en
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Short-container-title:Pharmaceuticals
Author:
Li Linying,
Lee ChanhwaORCID,
Cruz DanielaORCID,
Krovi SaiORCID,
Hudgens Michael,
Cottrell Mackenzie,
Johnson Leah
Abstract
Controlled drug delivery systems can provide sustained release profiles, favorable pharmacokinetics, and improved patient adherence. Here, a reservoir-style implant comprising a biodegradable polymer, poly(ε-caprolactone) (PCL), was developed to deliver drugs subcutaneously. This work addresses a key challenge when designing these implantable drug delivery systems, namely the accurate prediction of drug release profiles when using different formulations or form factors of the implant. The ability to model and predict the release behavior of drugs from an implant based on their physicochemical properties enables rational design and optimization without extensive and laborious in vitro testing. By leveraging experimental observations, we propose a mathematical model that predicts the empirical parameters describing the drug diffusion and partitioning processes based on the physicochemical properties of the drug. We demonstrate that the model enables an adequate fit predicting empirical parameters close to experimental values for various drugs. The model was further used to predict the release performance of new drug formulations from the implant, which aligned with experimental results for implants exhibiting zero-order release kinetics. Thus, the proposed empirical models provide useful tools to inform the implant design to achieve a target release profile.
Funder
U.S. President’s Emergency Plan for AIDS Relief
National Institute of Allergy and Infectious Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health
University of North Carolina at Chapel Hill Center for AIDS Research
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine
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