4.3 Article

Development of a mechanism and an accurate and simple mathematical model for the description of drug release: Application to a relevant example of acetazolamide-controlled release from a bio-inspired elastin-based hydrogel

Publisher

ELSEVIER
DOI: 10.1016/j.msec.2015.12.050

Keywords

Mathematical model; Polymeric drug delivery systems; Hydrogels; Controlled release/delivery; Biomaterials

Funding

  1. EU via the European Social Fund (FSE)
  2. Operative program of Castilla y Leon
  3. JCyL, via the Consejeria de Educacion
  4. European regional development fund (ERDF)
  5. MINECO [MAT2013-41723-R, MAT2013-42473-R, PRI-PIBAR-2011-1403, MAT2012-38043]
  6. JCyL [VA155A12, VA152A12, VA244U13]
  7. CIBER-BBN
  8. Instituto de Salud Carlos III under the Network Center of Regenerative Medicine and Cellular Therapy of Castilla and Leon
  9. CONICET (Argentina)
  10. CIUNSa [2199/0]
  11. CONICET [PIP 11220120100313CO]
  12. ANPCyT [PICT 2012-2643]
  13. ANPCyT-MICINN (Argentina-Spain) [PICT 2011-2751]

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Transversality between mathematical modeling, pharmacology, and materials science is essential in order to achieve controlled-release systems with advanced properties. In this regard, the area of biomaterials provides a platform for the development of depots that are able to achieve controlled release of a drug, whereas pharmacology strives to find new therapeutic molecules and mathematical models have a connecting function, providing a rational understanding by modeling the parameters that influence the release observed. Herein we present a mechanism which, based on reasonable assumptions, explains the experimental data obtained very well. In addition, we have developed a simple and accurate lumped kinetics model to correctly fit the experimentally observed drug-release behavior. This lumped model allows us to have simple analytic solutions for the mass and rate of drug release as a function of time without limitations of time or mass of drug released, which represents an important step-forward in the area of in vitro drug delivery when compared to the current state of the art in mathematical modeling. As an example, we applied the mechanism and model to the release data for acetazolamide from a recombinant polymer. Both materials were selected because of a need to develop a suitable ophthalmic formulation for the treatment of glaucoma. The in vitro release model proposed herein provides a valuable predictive tool for ensuring product performance and batch-to-batch reproducibility, thus paving the way for the development of further pharmaceutical devices. (C) 2015 Elsevier B.V. All rights reserved.

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