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Sucrose ester-based biocompatible microemulsions as vehicles for aceclofenac as a model drug: formulation approach using D-optimal mixture design
Authors:Marija N Todosijević  Nebojša D Cekić  Miroslav M Savić  Mirjana Gašperlin  Danijela V Ranđelović  Snežana D Savić
Institution:1. Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade, 11221, Serbia
2. Faculty of Technology, University of Ni?, Leskovac, 16000, Serbia
3. DCP Hemigal, Leskovac, 16000, Serbia
4. Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, 11221, Serbia
5. Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, 1000, Ljubljana, Slovenia
6. ICTM—Institute of Microelectronic Technologies, University of Belgrade, Belgrade, 11000, Serbia
Abstract:We assessed the functionality of sucrose esters (sucrose laurate, myristate, palmitate, and stearate), relatively innocuous nonionic surfactants, in formulation of biocompatible microemulsions. The putative influence of surfactant structure on the extension of microemulsion region was explored through the construction of the pseudo-ternary phase diagrams for the isopropyl myristate/sucrose ester-isopropyl alcohol/water system, using the titration method and mixture experimental approach. Minor changes in surfactant tail length strongly affected the microemulsion area boundaries. D-optimal mixture design proved to be highly applicable in detecting the microemulsion regions. Examination of conductivity, rheology, and thermal behavior of the selected sucrose laurate and sucrose myristate-based microemulsions, upon dilution with water, indicated existence of percolation threshold and suggested the phase inversion from water-in-oil to oil-in-water via a bicontinuous structure. Atomic force micrographs confirmed the suggested type of microemulsions and were valuable in further exploring their inner structure. The solubilization capacity of aceclofenac as a model drug has decreased as the water volume fraction in microemulsion increased. High surfactant concentration and the measured solubility of aceclofenac in microemulsion components suggested that the interfacial film may mostly contribute to aceclofenac solubilization.
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