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Premix Membrane Emulsification: Preparation and Stability of Medium-Chain Triglyceride Emulsions with Droplet Sizes below 100 nm
Authors:Lara El-Hawari  Heike Bunjes
Institution:1.Institut für Pharmazeutische Technologie und Biopharmazie, Technische Universität Braunschweig, Mendelssohnstraße 1, D-38106 Braunschweig, Germany;2.Zentrum für Pharmaverfahrenstechnik (PVZ), Franz-Liszt-Straße 35a, D-38106 Braunschweig, Germany
Abstract:Premix membrane emulsification is a promising method for the production of colloidal oil-in-water emulsions as drug carrier systems for intravenous administration. The present study investigated the possibility of preparing medium-chain triglyceride emulsions with a mean particle size below 100 nm and a narrow particle size distribution using sucrose laurate as an emulsifier. To manufacture the emulsions, a coarse pre-emulsion was repeatedly extruded through alumina membranes (Anodisc) of 200 nm, 100 nm and 20 nm nominal pore size. When Anodisc membranes with 20 nm pore size were employed, nanoemulsions with z-average diameters of about 50 nm to 90 nm and polydispersity indices smaller than 0.08 could be obtained. Particle growth due to Ostwald ripening was observed over 18 weeks of storage. The Ostwald ripening rate linearly depended on the emulsifier concentration and the concentration of free emulsifier, indicating that micelles in the aqueous phase accelerated the Ostwald ripening process. Long-term stability of the nanoemulsions could be achieved by using a minimised emulsifier concentration or by osmotic stabilisation with soybean oil added in a mass ratio of 1:1 to the lipid phase.
Keywords:nanoemulsion  colloidal drug carriers  premix membrane emulsification  alumina membrane  Ostwald ripening  sucrose laurate  ultrahydrophobe
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