The physical stability of thermally-stressed phospholipid-based emulsions containing methyl, propyl and heptyl parabens as model drugs.
The objectives of the studies presented herein was to investigate the mechanisms of emulsion instability under thermal stress (121 degrees C) by evaluating the effects of a lipophilic drug dissolved in the internal phase of an oil-in-water (o/w) emulsion on growth rate suppression and the apparent microviscosity. Model drugs used were methyl, propyl and heptyl paraben. The o/w emulsions were prepared using medium chain triglycerides as an internal phase in aqueous glycerol solutions emulsified with phospholipids. Concentrations of paraben in the internal phase varied from 0.2-0.8 M. Microfluidization was used to reduce the droplet size to the submicron range. Microviscosity was calculated from the measured anisotropy of a fluorophore probe (1,6-phenyl-1,3,5-hexatriene) using a modified Perrin's equation. Emulsion aliquots were subjected to thermal stressed at 121 degrees C the droplet growth rate was determined from periodic measurements of the mean droplet diameter using photon correlation spectroscopy. The growth rate decreased in the presence of parabens. Maximal growth suppression occurred at paraben concentrations of 0.4 M. However in deference to theoretical predictions of the effects of increasing co-solute concentrations based on Ostwalt ripening, the droplet growth rates increased at concentrations greater than 0.4M. The logarithm of the growth rate was linearly correlated to the interfacial rigidity (inverse microviscosity) of the emulsion which suggests that coalescence rather than molecular diffusion was primarily responsible for emulsion instability under the conditions studied.
Zhang
Xiaoguang
X
Division of Pharmaceutics, College of Pharamacy, The University of Iowa, Iowa City, IA 52242, USA.
Kirsch
Lee E
LE
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004355:Drug Stability; D004655:Emulsions; D006358:Hot Temperature; D008956:Models, Chemical; D010226:Parabens / Q000737:chemistry*; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D014783:Viscosity
D004655:Emulsions; D010226:Parabens; D010743:Phospholipids; C015358:methylparaben; C481602:heptylparaben; C006068:propylparaben