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Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling

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Abstract

The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.

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Acknowledgments

The authors would like to express their gratitude to the Spanish Ministry of Economy and Competitiveness and FEDER Funds (European Union) for the support of the project MAT2012-38044-C03-01 and MAT2012- 38044-C03-02 and the Regional Government of Andalusia for the support of the project P12-FQM-1553.

Financial support for this work was provided by School of Life Sciences at the University of Applied Sciences and Arts (Muttenz, Switzerland) and the University of Seville (Seville, Spain).

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Authors and Affiliations

  1. Department of Pharmacy and Pharmaceutical Technology, University of Seville, C/Profesor García González 2, 41012, Seville, Spain

    María Dolores Campiñez & Isidoro Caraballo

  2. Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056, Basel, Switzerland

    Maxim Puchkov

  3. Institute for Pharma Technology, University of Applied Sciences Northwestern Switzerland, Muttenz, Switzerland

    Martin Kuentz

Authors
  1. María Dolores Campiñez
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  2. Isidoro Caraballo
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  3. Maxim Puchkov
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  4. Martin Kuentz
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Correspondence to María Dolores Campiñez.

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Campiñez, M.D., Caraballo, I., Puchkov, M. et al. Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling. AAPS PharmSciTech 18, 1544–1553 (2017). https://doi.org/10.1208/s12249-016-0613-0

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  • DOI: https://doi.org/10.1208/s12249-016-0613-0

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