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Mechanisms Controlling Theophylline Release from Ethanol-Resistant Coated Pellets

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ABSTRACT

Purpose

To elucidate the mass transport mechanisms controlling drug release from recently proposed, ethanol-resistant, polymeric film coatings.

Methods

Theophylline matrix pellets were coated with ethylcellulose: guar gum blends. Drug release from single pellets and ensembles of pellets was measured in various release media. Changes in the systems’ morphology, composition and mechanical properties were monitored using SEM, gravimetrical analysis and a texture analyzer. Based on the obtained experimental results a mechanistically realistic mathematical model was identified and used to quantitatively predict drug release from coated pellets in ethanol-free and ethanol-containing bulk fluids.

Results

Drug diffusion though the intact polymeric film coatings is likely to be the dominant mass transport mechanism in the investigated systems, irrespective of the ethanol content in the surrounding environment. An appropriate solution of Fick’s law could be used to quantitatively predict theophylline release from pellets coated with different ethylcellulose:guar gum blends at different coating levels. Importantly, independent experiments confirmed the theoretical predictions.

Conclusions

In silico simulations can help facilitating the optimization of the novel ethanol-resistant polymeric film coatings, avoiding time-consuming and cost-intensive series of trial-and-error experiments. The presence/absence of ethanol does not affect the underlying drug release mechanisms.

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Acknowledgments And Disclosures

Two of the authors are employees of FMC BioPolymer, the company commercializing Aquacoat® ECD 30.

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Authors and Affiliations

  1. College of Pharmacy, Univ. Lille Nord de France, 3 Rue du Prof. Laguesse, 59006, Lille, France

    Y. Rosiaux, C. Velghe, S. Muschert, F. Siepmann & J. Siepmann

  2. INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, 3 Rue du Prof. Laguesse, 59006, Lille, France

    Y. Rosiaux, C. Velghe, S. Muschert, F. Siepmann & J. Siepmann

  3. FMC BioPolymer, Avenue Mounier 83, 1200, Brussels, Belgium

    B. Leclercq

  4. FMC BioPolymer, 801 Princeton South Corp Ctr, Ewing, New Jersey, 08628, USA

    R. Chokshi

Authors
  1. Y. Rosiaux
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  2. C. Velghe
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  3. S. Muschert
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  4. R. Chokshi
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  5. B. Leclercq
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  6. F. Siepmann
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  7. J. Siepmann
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Correspondence to J. Siepmann.

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Rosiaux, Y., Velghe, C., Muschert, S. et al. Mechanisms Controlling Theophylline Release from Ethanol-Resistant Coated Pellets. Pharm Res 31, 731–741 (2014). https://doi.org/10.1007/s11095-013-1194-1

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  • DOI: https://doi.org/10.1007/s11095-013-1194-1

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