Thermodynamic investigation of the interaction between cyclodextrins and preservatives - Application and verification in a mathematical model to determine the needed preservative surplus in aqueous cyclodextrin formulations

René Holm; Niels Erik Olesen; Signe Dalgaard Alexandersen; Birgitte N Dahlgaard; Peter Westh; Huiling Mu

doi:10.1016/j.ejps.2015.09.011

Thermodynamic investigation of the interaction between cyclodextrins and preservatives - Application and verification in a mathematical model to determine the needed preservative surplus in aqueous cyclodextrin formulations

René Holm, Niels Erik Olesen, Signe Dalgaard Alexandersen, Birgitte N Dahlgaard, Peter Westh, Huiling Mu

7 Citationer (Scopus)

Abstract

Preservatives are inactivated when added to conserve aqueous cyclodextrin (CD) formulations due to complex formation between CDs and the preservative. To maintain the desired conservation effect the preservative needs to be added in apparent surplus to account for this inactivation. The purpose of the present work was to establish a mathematical model, which defines this surplus based upon knowledge of stability constants and the minimal concentration of preservation to inhibit bacterial growth. The stability constants of benzoic acid, methyl- and propyl-paraben with different frequently used βCDs were determined by isothermal titration calorimetry. Based upon this knowledge mathematical models were constructed to account for the equilibrium systems and to calculate the required concentration of the preservations, which was evaluated experimentally based upon the USP/Ph. Eur./JP monograph. The mathematical calculations were able to predict the needed concentration of preservation in the presence of CDs; it clearly demonstrated the usefulness of including all underlying chemical equilibria in a mathematical model, such that the formulation design can be based on quantitative arguments.

Originalsprog	Engelsk
Tidsskrift	European Journal of Pharmaceutical Sciences
Vol/bind	87
Sider (fra-til)	22-9
Antal sider	8
ISSN	0928-0987
DOI	https://doi.org/10.1016/j.ejps.2015.09.011
Status	Udgivet - 25 maj 2016

Adgang til dokumentet

10.1016/j.ejps.2015.09.011

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Citationsformater

Holm, R., Olesen, N. E., Alexandersen, S. D., Dahlgaard, B. N., Westh, P., & Mu, H. (2016). Thermodynamic investigation of the interaction between cyclodextrins and preservatives - Application and verification in a mathematical model to determine the needed preservative surplus in aqueous cyclodextrin formulations. European Journal of Pharmaceutical Sciences, 87, 22-9. https://doi.org/10.1016/j.ejps.2015.09.011

Thermodynamic investigation of the interaction between cyclodextrins and preservatives - Application and verification in a mathematical model to determine the needed preservative surplus in aqueous cyclodextrin formulations. / Holm, René; Olesen, Niels Erik; Alexandersen, Signe Dalgaard et al.
I: European Journal of Pharmaceutical Sciences, Bind 87, 25.05.2016, s. 22-9.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Holm, R, Olesen, NE, Alexandersen, SD, Dahlgaard, BN, Westh, P & Mu, H 2016, 'Thermodynamic investigation of the interaction between cyclodextrins and preservatives - Application and verification in a mathematical model to determine the needed preservative surplus in aqueous cyclodextrin formulations', European Journal of Pharmaceutical Sciences, bind 87, s. 22-9. https://doi.org/10.1016/j.ejps.2015.09.011

Holm R, Olesen NE, Alexandersen SD, Dahlgaard BN, Westh P, Mu H. Thermodynamic investigation of the interaction between cyclodextrins and preservatives - Application and verification in a mathematical model to determine the needed preservative surplus in aqueous cyclodextrin formulations. European Journal of Pharmaceutical Sciences. 2016 maj 25;87:22-9. doi: 10.1016/j.ejps.2015.09.011

Holm, René ; Olesen, Niels Erik ; Alexandersen, Signe Dalgaard et al. / Thermodynamic investigation of the interaction between cyclodextrins and preservatives - Application and verification in a mathematical model to determine the needed preservative surplus in aqueous cyclodextrin formulations. I: European Journal of Pharmaceutical Sciences. 2016 ; Bind 87. s. 22-9.

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title = "Thermodynamic investigation of the interaction between cyclodextrins and preservatives - Application and verification in a mathematical model to determine the needed preservative surplus in aqueous cyclodextrin formulations",

abstract = "Preservatives are inactivated when added to conserve aqueous cyclodextrin (CD) formulations due to complex formation between CDs and the preservative. To maintain the desired conservation effect the preservative needs to be added in apparent surplus to account for this inactivation. The purpose of the present work was to establish a mathematical model, which defines this surplus based upon knowledge of stability constants and the minimal concentration of preservation to inhibit bacterial growth. The stability constants of benzoic acid, methyl- and propyl-paraben with different frequently used βCDs were determined by isothermal titration calorimetry. Based upon this knowledge mathematical models were constructed to account for the equilibrium systems and to calculate the required concentration of the preservations, which was evaluated experimentally based upon the USP/Ph. Eur./JP monograph. The mathematical calculations were able to predict the needed concentration of preservation in the presence of CDs; it clearly demonstrated the usefulness of including all underlying chemical equilibria in a mathematical model, such that the formulation design can be based on quantitative arguments.",

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AU - Olesen, Niels Erik

AU - Alexandersen, Signe Dalgaard

AU - Dahlgaard, Birgitte N

AU - Westh, Peter

AU - Mu, Huiling

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AB - Preservatives are inactivated when added to conserve aqueous cyclodextrin (CD) formulations due to complex formation between CDs and the preservative. To maintain the desired conservation effect the preservative needs to be added in apparent surplus to account for this inactivation. The purpose of the present work was to establish a mathematical model, which defines this surplus based upon knowledge of stability constants and the minimal concentration of preservation to inhibit bacterial growth. The stability constants of benzoic acid, methyl- and propyl-paraben with different frequently used βCDs were determined by isothermal titration calorimetry. Based upon this knowledge mathematical models were constructed to account for the equilibrium systems and to calculate the required concentration of the preservations, which was evaluated experimentally based upon the USP/Ph. Eur./JP monograph. The mathematical calculations were able to predict the needed concentration of preservation in the presence of CDs; it clearly demonstrated the usefulness of including all underlying chemical equilibria in a mathematical model, such that the formulation design can be based on quantitative arguments.

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