مستخلص: |
Laser light scattering was used to monitor particle size and polydispersity of several water-in-oil (w/o) microemulsion formulations upon dilution with excess of the dispersed (aqueous) phase to induce phase inversion 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 were investigated. In addition, the particle size of diluted formulations 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 or 37°C produced particles with similar size unless the microemulsion was solid at ambient temperature where significant effect on particle size upon dilution was observed. As expected from the non-ionic nature of the investigated microemulsions, using different physiologically relevant diluent solutions the particle size of the diluted microemulsion was found to be unaffected by pH and/or ionic strength. Dilution with a micellar sodium deoxycholate doubled the particle size and polydispersity of the diluted microemulsion, presumably as a result of physical interactions. The presence of a small peptide SK& F 110679 (Mol. Wt = 850) in different microemulsions prior to dilution, at levels 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 stored 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. |