International Journal of Pharmaceutics 2015-01-01

Kinetically stable propofol emulsions with reduced free drug concentration for intravenous delivery.

Robert Damitz, Anuj Chauhan

Index: Int. J. Pharm. 486 , 232-41, (2015)

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Abstract

Intravenous injections of propofol emulsions are accompanied by pain likely due to the interaction of the dissolved drug with endothelial cells of the vasculature. It is commonly hypothesized that reducing the aqueous phase concentration of propofol could reduce pain.To minimize the propofol concentration in the aqueous phase, we developed stable oil-in-water emulsions with excipient oil mixtures that have an increased partition coefficient for propofol. We then explored the emulsion stability by measuring size distributions after extended durations of shelf storage and also after freeze-thaw cycling. The effects of oil type, surfactant and salt concentration on emulsion stability were also explored.Small chain oils like ethyl butyrate exhibit high drug partitioning but poor stability, while larger molecules such as soybean oil exhibit lower partitioning but excellent emulsion stability. Emulsions with mixtures of soybean oil and ethyl butyrate are stable for longer than a year, resistant to freeze-thaw cycling, and reduce aqueous drug concentrations of propofol twofold compared to pure soybean oil emulsions.Oil-in-water emulsions of propofol formulated with mixtures of ethyl butyrate and soybean oil are kinetically stable and significantly reduce the aqueous phase drug concentration making them promising candidates for future propofol therapies.Copyright © 2015 Elsevier B.V. All rights reserved.