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
| Autor: | René Holm, Niels Erik Olesen, Huiling Mu, Signe Dalgaard Alexandersen, Birgitte N. Dahlgaard, Peter Westh |
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| Rok vydání: | 2016 |
| Předmět: |
chemistry.chemical_classification
Cyclodextrins Work (thermodynamics) Preservative Aqueous solution Mathematical model Cyclodextrin Chemistry Pharmaceutical Preservatives Pharmaceutical Pharmaceutical Science Thermodynamics Isothermal titration calorimetry 02 engineering and technology Models Theoretical 010402 general chemistry 021001 nanoscience & nanotechnology 01 natural sciences 0104 chemical sciences chemistry.chemical_compound chemistry Chemical engineering Stability constants of complexes 0210 nano-technology Benzoic acid |
| Zdroj: | European Journal of Pharmaceutical Sciences. 87:22-29 |
| ISSN: | 0928-0987 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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