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Biowaiver or Bioequivalence: Ambiguity in Sildenafil Citrate BCS Classification

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Abstract

The aim of the present study is to contribute to the scientific characterization of sildenafil citrate according to the Biopharmaceutics Classification System, following the World Health Organization (WHO) guidelines for biowaivers. The solubility and intestinal permeability data of sildenafil citrate were collected from literature; however, the experimental solubility studies are inconclusive and its “high permeability” suggests an API in the borderline of BCS Class I and Class II. The pH-solubility profile was determined using the saturation shake-flask method over the pH range of 1.2–6.8 at a temperature of 37 °C in aqueous media. The intestinal permeability was determined in rat by a closed-loop in situ perfusion method (the Doluisio technique). The solubility of sildenafil citrate is pH-dependent and at pH 6.8 the dose/solubility ratio obtained does not meet the WHO criteria for “high solubility.” The high permeability values obtained by in situ intestinal perfusion in rat reinforce the published permeability data for sildenafil citrate. The experimental results obtained and the data available in the literature suggest that sildenafil citrate is clearly a Class II of BCS, according to the current biopharmaceutics classification system and WHO guidance.

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Acknowledgments

We thank to MEDSOL Laboratories (Havana, Cuba) for the generous donation of sildenafil citrate. We also thank to Centro de Investigación y Desarrollo de Medicamentos (CIDEM) for the collaboration in this study.

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Authors and Affiliations

  1. Unit of Modeling and Experimental Biopharmaceutics, Centre of Chemical Bioactive, Central University of Las Villas, 54830, Santa Clara, Villa Clara, Cuba

    Claudia Miranda, Zenia Pérez-Rodríguez, Rosario Hernández-Armengol, Yaidel Quiñones-García, Tania Betancourt-Purón & Miguel Ángel Cabrera-Pérez

  2. Department of Pharmacy and Pharmaceutical Technology, University of Valencia, 46100, Burjassot, Valencia, Spain

    Miguel Ángel Cabrera-Pérez

  3. Department of Engineering, Area of Pharmacy and Pharmaceutical Technology, Miguel Hernández University, 03550 Sant Joan d’Alacant, Alicante, Spain

    Miguel Ángel Cabrera-Pérez

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  1. Claudia Miranda
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  2. Zenia Pérez-Rodríguez
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  3. Rosario Hernández-Armengol
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Correspondence to Miguel Ángel Cabrera-Pérez.

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Miranda, C., Pérez-Rodríguez, Z., Hernández-Armengol, R. et al. Biowaiver or Bioequivalence: Ambiguity in Sildenafil Citrate BCS Classification. AAPS PharmSciTech 19, 1693–1698 (2018). https://doi.org/10.1208/s12249-018-0982-7

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