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1.  Particle size analysis of concentrated phospholipid microemulsions: II. Photon correlation spectroscopy 
AAPS PharmSci  2000;2(3):1-10.
The solvated droplet size of concentrated water-in-oil (w/o) microemulsions prepared frome egg and soy lecithin/water/isopropyl myristate and containing short-chain alcohol cosurfactants has been determined using photon correlation spectroscopy (PCS). The effect of increasing the water volume fraction (from 0.04 to 0.26) on the solvated size of the w/o droplets at 298 K has been investigated at 4 different surfactant/cosurfactant weight ratios (Km of 1∶1, 1.5∶1, 1.77∶1, and 1.94∶1); in all cases the total surfactant/cosurfactant concentration was kept constant at 25% w/w. In the case of the microemulsions prepared from egg lecthin, the diffusion coefficients obtained from PCS measurements were corrected for interparticulate interactions using a hard-sphere model that necessitated estimation of the droplet volume fractions, which in the present study were obtained from earlier total intensity light-scattering (TILS) studies performed on the same systems. Once corrected for hard-sphere interactions, the diffusion coefficients were converted to solvated radii using the Stokes-Einstein equation assuming spherical microemulsion droplets. For both egg and soy lecithin systems, no microemulsion droplets were detected at water concentrations less than 9 wt% regardless of the alcohol and Km used, suggesting that at low concentrations of added water, cosolvent systems were formed. At higher water concentrations, however, microemulsion droplets were observed. The changes in droplet size followed the expected trend in that for a fixed Km the size of the microemulsion droplets increased with increasing volume fraction of water. At constant water concentration, droplet size decreased slightly upon increasing Km. Interestingly, only small differences in size were seen upon changing the type of alcohol used. The application of the hard-sphere model to account for interparticulate interactions for the egg lecithin systems indicated that the uncorrected diffusion coefficients underestimated particle size by a factor of slightly less than 2. Reassuringly, the corrected droplet sizes agreed very well with those obtained from our earlier TILS study.
doi:10.1208/ps020319
PMCID: PMC2761130  PMID: 11741235
2.  Particle size analysis of concentrated phospholipid microemulsions: I. Total intensity light scattering 
AAPS PharmSci  2000;2(2):27-39.
Water-in-oil phospholipid microemulsions prepared from a constant total surfactant/cosurfactant concentration of 25 wt% at four different lecithin/alcohol weight ratios (Km of 1∶1, 1.5∶1, 1.77∶1, and 1.94∶1) and containing water concentrations (or volume fractions) ranging from 2.0 to 26 wt% (or 0.04 to 0.26) have been examined at 298 K using total intensity light scattering. The data obtained were analysed using the hard-sphere model of Percus-Yevick, modified to account for the partitioning of the alcohol between the various phases. The light-scattering results showed that, regardless of the Km or the alcohol used, a minimum water concentration of at least 9 wt% was required for the formation of a microemulsion; although this value was reasonably constant for each of the alcohols investigated, there was a tendency for a slightly higher concentration of water to be required for microemulsion formation at higher Km values. Simple calculations suggested that a microemulsion was formed only when sufficient water was present to satisfy the hydration of both the phospholipid head groups and the hydroxyl groups of the cosurfactant associated with the droplet. At water concentrations lower than this minimum value, a cosolvent system was observed. In all systems above this minimum concentration, as the concentration of water increased, the size of the microemulsion droplets also increased. Surprisingly, however, there was little difference in the size of the microemulsion droplets obtained with the different alcohols, regardless of the Km, although for a particular alcohol there was some indication that the higher Km systems produced the slightly smaller droplets for an equivalent water concentration. There was also a suggestion that the more hydrophobic alcohols produced slightly smaller droplets than the more polar alcohols at the same Km.
doi:10.1208/ps020213
PMCID: PMC2751027  PMID: 11741229

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