M. Jayne Lawrence

Microemulsion-based media as novel drug delivery systems☆

Microemulsions are clear, stable, isotropic mixtures of oil, water and surfactant, frequently in combination with a cosurfactant. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drug delivery vehicles by incorporating a wide range of drug molecules. In order to appreciate the potential of microemulsions as delivery vehicles, this review gives an overview of the formation and phase behaviour and characterization of microemulsions. The use of microemulsions and closely related microemulsion-based systems as drug delivery vehicles is reviewed, with particular emphasis being placed on recent developments and future directions.

Gelatin-stabilised microemulsion-based organogels : rheology and application in iontophoretic transdermal drug delivery

Gelatin-containing microemulsion-based organogels (MBGs) have been formulated using pharmaceutically acceptable surfactants and oils such as Tween 85 and isopropyl myristate. MBG formulations were subject to rheological study and their utility in transdermal drug delivery examined. Unlike most organogels, MBGs are electrically conducting and have been successfully employed in this study for the iontophoretic delivery of a model drug through excised pig skin. Iontophoresis using MBGs gave substantially higher release rates for sodium salicylate compared to passive diffusion, and fluxes were proportional to the drug loading and the current density. MBGs provide a convenient means of immobilising the drug and are rheologically similar to their hydrogel counterparts at comparable gelatin concentrations. MBGs also appear to offer improved microbial resistance in comparison to aqueous solution or hydrogels.

Surfactant systems: Microemulsions and vesicles as vehicles for drug delivery

SummaryAlthough surfactants have been widely used as pharmaceutical adjuvants for many years, it is only relatively recently that their phase structures have been seriously considered as drug delivery vehicles per se. This review highlights the work to date investigating the potential of microemulsions as drug cariers and also reports on preliminary studies performed on the use of vesicles formed from nonionic surfactants.

A comparison of the incorporation of model steroids into non-ionic micellar and microemulsion systems.

Abstract— The incorporation of testosterone and two of its esters, and progesterone and one of its esters (log Poct varying from 3·3 to 6·9) into 2% w/w soybean oil/Brij 96 microemulsions and Brij 96 surfactant systems has been examined. Possible sites of incorporation have been investigated. The drug carrying improvement of an oil‐in‐water microemulsion over a micellar system appears to depend on the solubility of the drug in the dispersed oil phase and is significant only for very lipophilic drugs.

Microemulsions as drug delivery vehicles

Microemulsions offer many promising features for their possible widespread use as vehicles for the delivery of drugs, as is evidenced by the recent introduction to the market of a microemulsion pre-concentrate for the oral delivery of cyclosporin. This vehicle has stimulated considerable interest in microemulsions and related systems, such as microemulsion-based lecithin gels. Much work is being centered around producing drug-containing microemulsions from materials that are suitable for use in humans.

Three-component non-ionic oil-in-water microemulsions using polyoxyethylene ether surfactants

Abstract Eight commercially available polyoxyethylene ether surfactants (CmEn) were investigated for their ability to produce three-component oil-in-water (o/w) microemulsions using a variety of dispersed oil phases. The resulting phase diagrams are presented. The areas of existence found show that, at room temperature, modification of three-component oil/CmEn surfactant/water systems alters o/w microemulsion formation in a complex way which is dependent on the relative size and structure of the surfactant hydrophobe, the number of attached ethylene oxide units and the nature of the oil phase to be incorporated.

On the hydration of the phosphocholine headgroup in aqueous solution

The hydration of the phosphocholine headgroup in 1,2-dipropionyl-sn-glycero-3-phosphocholine (C(3)-PC) in solution has been determined by using neutron diffraction enhanced with isotopic substitution in combination with computer simulation techniques. The atomic scale hydration structure around this head group shows that both the -N(CH(3))(3) and -CH(2) portions of the choline headgroup are strongly associated with water, through a unique hydrogen bonding regime, where specifically a hydrogen bond from the C-H group to water and a strong association between the water oxygen and N(+) atom in solution have both been observed. In addition, both PO(4) oxygens (P=O) and C=O oxygens are oversaturated when compared to bulk water in that the average number of hydrogen bonds from water to both X=O oxygens is about 2.5 for each group. That water binds strongly to the glycerol groups and is suggestive that water may bind to these groups when phosophotidylcholine is embedded in a membrane bilayer.

Light-scattering investigations on dilute nonionic oil-in-water microemulsions

Dilute 3-component nonionic oil-in-water microemulsions formulated with either a polyoxyethylene surfactant (C18∶1E10 or C12E10) or the alkylamine-N-oxide surfactant, DDAO (C12AO), and containing either a triglyceride or an ethyl ester oil have been examined using dynamic and static light-scattering techniques. Analysis of the results showed distinct differences in the tested oils mode of incorporation into the microemulsion droplets, with both the molecular volume of the oil and the hydrophobic chain length of the surfactant being important. For example, microemulsions formulated by C18∶1E10 and containing one of the larger molecular volume oils (that is, either a triglyceride, Miglyol 812, or soybean oil) or the ethyl ester of fatty acid oil, ethyl oleate, exhibited first a decrease and then an increase in hydrodynamic size and surfactant aggregation number, suggesting that the asymmetric C18∶1E10 micelles became spherical upon the addition of a small amount of oil and grew thereafter because of further oil being incorporated into the core of the spherical microemulsion droplet. A similar conclusion of sphericity could not be drawn for microemulsions stabilized by C18∶1E10 and containing one of the oils smaller in molecular volume (namely tributyrin, ethyl butyrate, or ethyl caprylate) where neither the aggregation number nor the hydrodynamic radius changed much upon the addition of oil. This result suggested that these oils were preferentially located in the interfacial surfactant monolayer, behaving in much the same way as a cosurfactant. A different trend of results, however, was seen for microemulsions prepared using C12E10 and C12AO, most likely because these surfactants produced approximately spherical micelles. In this case, the microemulsions containing the oils larger in molecular volume tended to exhibit an increase in surfactant aggregation number and hydrodynamic size, suggesting the growth of spherical micelles, while the smaller oils (in particular ethyl butyrate) caused a significant decrease in surfactant aggregation number incompatible with their being incorporated into the centre of the droplet, suggesting that the oils were being located in the interfacial surfactant monolayer. These results suggest that the various oils are incorporated into the microemulsions in very different ways.

Nonequilibrium Effects in Self-Assembled Mesophase Materials: Unexpected Supercooling Effects for Cubosomes and Hexosomes

Polar lipids often exhibit equilibrium liquid crystalline structures in excess water, such as the bicontinuous cubic phases (Q(II)) at low temperatures and inverse hexagonal phase (H(II)) at higher temperatures. In this study, the equilibrium and nonequilibrium phase behavior of glyceryl monooleate (GMO) and phytantriol (PHYT) systems in excess water were investigated using both continuous heating and cooling cycles, and rapid temperature changes. Evolution of the phase structure was followed using small-angle X-ray scattering (SAXS). During cooling, not only was supercooling of the liquid crystalline systems by up to 25 degrees C observed, but evidence for nonequilibrium phase structures (not present on heating; such as the gyroid cubic phase only present at low water content in equilibrium) was also apparent. The nonequilibrium phases were surprisingly stable, with return to equilibrium structure for dispersed submicrometer sized particle systems taking more than 13 h in some cases. Inhibition of phase nucleation was the key to greater supercooling effects observed for the dispersed particles compared to the bulk systems. These findings highlight the need for continued study into the nonequilibrium phase structures for these types of systems, as this may influence performance in applications such as drug delivery.

Particle size analysis of concentrated phospholipid microemulsions II. Photon correlation spectroscopy.

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 (K m 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 K m 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 K m the size of the microemulsion droplets increased with increasing volume fraction of water. At constant water concentration, droplet size decreased slightly upon increasing K m. 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.