The Effect of Surfactants and pH Modifying Agents on the Dissolution and Permeation of Pimobendan

Authors

  • Petra Tőzsér
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rakpart 3., H-1111 Budapest, Hungary
  • Luca L. Kovács
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rakpart 3., H-1111 Budapest, Hungary
  • Szabina Kádár
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rakpart 3., H-1111 Budapest, Hungary
  • Dóra Csicsák
    Affiliation
    Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Semmelweis University, Hőgyes Endre u. 9., H-1092 Budapest, Hungary
  • Péter Sóti
    Affiliation
    Lavet Ltd., Batthyány utca 6., H-2143 Kistarcsa, Hungary
  • Gergely Völgyi
    Affiliation
    Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Semmelweis University, Hőgyes Endre u. 9., H-1092 Budapest, Hungary
  • Bálint Sinkó
    Affiliation
    Pion Inc., Billerica, 10 Cook Street, Massachusetts 01821, USA
  • Zsombor K. Nagy
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rakpart 3., H-1111 Budapest, Hungary
  • Enikő Borbás
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rakpart 3., H-1111 Budapest, Hungary
https://doi.org/10.3311/PPch.20970

Abstract

Solubility and permeability are key parameters for establishing in vitro-in vivo correlation for poorly water-soluble active pharmaceutical ingredients (APIs). Recent studies demonstrate that not only solubility, but also effective permeability of the API may change due to the addition of solubilizing agents, and there is a certain mathematical relation between these physicochemical parameters. The aim of this study was to show the importance of early screening of solubility and permeability in presence of additives in order to achieve the expected bioavailability of the API. In this work, the effect of surfactants and microenvironmental pH modifiers were in focus, and pimobendan was chosen as model drug.
In the case of pH modifiers, the equilibrium solubility of the API increased, while the permeability decreased significantly. No negative effect was observed for two surfactants at low additive levels, but these two additives also exhibited a slightly negative effect on permeability when used at higher concentrations. In the simultaneous dissolution-permeation studies the surfactants-containing formulation was found to have slightly higher flux than the pH-modifier-containing one. It can be due to the phenomenon that the dissolution of the active substance can be enhanced by these surfactants without any significant permeability reducing effect.
The results obtained from the present study clearly demonstrate the importance of studying drug-additive interactions in every step of formulation development and based on these, the selection of the appropriate quality and quantity of additives. In addition, the results also underline the significance of performing simultaneous dissolution-permeation studies to predict bioavailability.

Keywords:

pimobendan, dissolution, permeation, absorption, flux, bioavailability

Citation data from Crossref and Scopus

Published Online

2023-02-01

How to Cite

Tőzsér, P., Kovács, L. L., Kádár, S., Csicsák, D., Sóti, P., Völgyi, G. “The Effect of Surfactants and pH Modifying Agents on the Dissolution and Permeation of Pimobendan”, Periodica Polytechnica Chemical Engineering, 67(1), pp. 1–10, 2023. https://doi.org/10.3311/PPch.20970

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