PARTICLE-SIZE DETERMINATION OF PHASE-INVERTED WATER-IN-OIL MICROEMULSIONS UNDER DIFFERENT DILUTION AND STORAGE-CONDITIONS

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.