Pp. Constantinides et Sh. Yiv, PARTICLE-SIZE DETERMINATION OF PHASE-INVERTED WATER-IN-OIL MICROEMULSIONS UNDER DIFFERENT DILUTION AND STORAGE-CONDITIONS, International journal of pharmaceutics, 115(2), 1995, pp. 225-234
Laser light scattering was used to monitor particle size and polydispe
rsity of several water-in-oil (w/o) microemulsion formulations upon di
lution with excess of the dispersed (aqueous) phase to induce phase in
version and generate oil-in-water (o/w) and/or water-in-oil-in-water (
w/o/w) emulsions. Factors affecting particle size, such as, the extent
and temperature of dilution, as well as, sample storage conditions we
re investigated. In addition, the particle size of diluted formulation
s incorporating a peptide (SK&F 110679) was determined and compared to
that of the peptide-free microemulsions. The extent of dilution had a
pronounced effect on particle size. Dilution at ambient temperature o
r 37 degrees C produced particles with similar size unless the microem
ulsion was solid at ambient temperature where significant effect on pa
rticle size upon dilution was observed. As expected from the non-ionic
nature of the investigated microemulsions, using different physiologi
cally relevant diluent solutions the particle size of the diluted micr
oemulsion was found to be unaffected by pH and/or ionic strength. Dilu
tion with a micellar sodium deoxycholate doubled the particle size and
polydispersity of the diluted microemulsion, presumably as a result o
f physical interactions. The presence of a small peptide SK&F 110679 (
Mol. Wt = 850) in different microemulsions prior to dilution, at level
s varied from 0.8 to 3.0 mg/ml of formulation, had no major effect on
the size of the inverted particle. Microemulsions which have been stor
ed at various temperatures for up to 70 days and then diluted, showed
no significant changes in particle size whereas the polydispersity was
increased upon storage.