The effects of surface charge and drug distribution on the chemical stability of paraben esters in intravenous lipid emulsions
Abstract
Numerous studies on the physical stability of emulsions have been reported but only a few works investigated the chemical stability of drugs in oilin-water (o/w) emulsions. These studies, however, used either a two-phase or three-phase kinetic model, which cannot explain many phenomena observed in these formulations such as the effect of surface charge on the chemical stability of drugs. The objective of this research was to investigate the effects of surface charge and drug distribution on the chemical stability of the drug in intravenous lipid emulsions. Methylparaben was added as a model drug in the 20% emulsions stabilized by egg phospholipid and a mixture of anionic or cationic surfactants. A four phase kinetic model was used in order to determine the fractional amount of a drug in each phase, to obtain the rate constants for the hydrolysis of a model drug in all phases, and finally to elucidate the effect of surface charge on drug stability. Solid phase extraction using a one-cc Oasis TM cartridge coupled with HPLC analysis allowed paraben esters to be effectively separated from other compounds in the tested emulsions and quantified. It was found that the surface charge of the oil droplets influenced the pH of the microenvironment of the oil droplets and thereby altered the rate of hydrolysis of methylparaben in o/w emulsions. As such, the stability of a drug in o/w emulsions could be either improved or reduced through the adjustment of the surface charge of the off droplets. The series of methyl-, ethyl-, propyl-, or butylparaben was incorporated into emulsions having various surface charges to study the effect of surface charge on solutes having different partition coefficients. The effect of surface charge on kobs was most pronounced in the emulsion containing methylparaben as evident from the largest magnitude of the slope of the plot of kobs vs zeta potential. The stability of propyl- and butylparaben were not affected by the surface charge of the oil droplets due to their high partition coefficient.
Degree
Ph.D.
Advisors
Hem, Purdue University.
Subject Area
Pharmaceuticals
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