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The Role of l-arginine in Inclusion Complexes of Omeprazole with Cyclodextrins

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Abstract

In this study, we investigate how the effect of l-arginine (ARG) and cyclodextrins upon omeprazole (OME) stability and solubility. The effect of the presence of ARG on the apparent stability constants (K1:1) of the inclusion complexes formed between OME and each cyclodextrin, β-cyclodextrin (βCD), and methyl-β-cyclodextrin (MβCD) is studied by phase solubility diagrams and nuclear magnetic resonance (NMR) spectroscopy. The interaction of OME with those cyclodextrins, in the presence of ARG, is characterized using NMR spectroscopy and molecular dynamics simulations. ARG significantly increases the drug solubility and complex stability, in comparison to inclusion complexes formed in its absence. The effect is more pronounced for the OME:βCD complex. ARG also contributes to a larger stability of OME when free in aqueous solution. The combination of ARG with cyclodextrins can represent an important tool to develop stable drug formulations.

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Acknowledgments

A.F. would like to acknowledge the grant SFRH/BD/19175/2004, and J.M.G.S. would like to acknowledge the grants SFRH/BD/17440/2004 and SFRH/BPD/46319/2008 from Fundação para a Ciência e Tecnologia (FCT, Portugal). The authors would like to thank Belmac Laboratory, S.A. (Madrid, Spain) for kindly donating of OME and Roquette (Lestrem, France) for providing the cyclodextrins used in this study, β-cyclodextrin, and methyl-β-cyclodextrin.

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Authors and Affiliations

  1. CICS, Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã, Portugal

    Ana Figueiras

  2. Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, Coimbra, Portugal

    Jorge M. G. Sarraguça & Alberto A. C. C. Pais

  3. REQUIMTE, Serviço de Química-Física da Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4099-030, Porto, Portugal

    Jorge M. G. Sarraguça

  4. Centro de Espectroscopia de RMN e Centro de Neurociências, Departamento de Bioquímica, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, Coimbra, Portugal

    Rui A. Carvalho

  5. CEF, Centro de Estudos Farmacêuticos, Departamento de Tecnologia Farmacêutica, Faculdade de Farmácia, Universidade de Coimbra, 3000-295, Coimbra, Portugal

    Ana Figueiras & J. Francisco Veiga

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  1. Ana Figueiras
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Correspondence to J. Francisco Veiga.

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Figueiras, A., Sarraguça, J.M.G., Pais, A.A.C.C. et al. The Role of l-arginine in Inclusion Complexes of Omeprazole with Cyclodextrins. AAPS PharmSciTech 11, 233–240 (2010). https://doi.org/10.1208/s12249-009-9375-2

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