Formulation of shear rate sensitive multiple emulsions.

This work mainly concentrates on the formulation of W/O/W multiple emulsions capable of breaking and releasing their inner aqueous phase under shear rates compatible with agroalimentary, pharmaceutical and cosmetic applications. Three kinds of multiple emulsions were studied: one with a high concentration of primary emulsion, not viscosified in the external aqueous phase; multiple emulsions gelified with a synthetic polymer (Carbopol 974P((R))); and other multiple emulsions thickened with chemically modified cellulose (hydroxypropylcellulose). The results of this study show the influence of the composition of the external aqueous phase of the emulsions on their fragmentation and release as a function of the shear rate. Despite these differences of behavior with respect to the shear rate, each emulsion fits to Taylor's theoretical framework, indicating that the bursting mechanisms of the globules under shear are the same whatever the composition of the multiple emulsions.

Stability study of W/O/W viscosified multiple emulsions.

Stable multiple emulsions with a small proportion of primary emulsion containing different viscosifying agents in the outer aqueous phase were formulated. The multiple systems were assessed by evaluating several parameters, such as the macroscopic aspect, droplet size, release rate, and accelerated stability under elevated temperatures. The effect of different viscosifying agents at different concentrations on the stability and the multiplicity of the multiple emulsions was examined. The viscosity increased by increasing the concentration of the viscosifying agents. It also appeared that the viscosifying agents increased the temperature stability of the multiple emulsions. As a result, the formulation viscosified with Klucel was more stable, while the one prepared with carbomer viscosified the outer phase at much lower concentrations with much better skin feel.

Phase behavior of fully hydrated DMPC-amphiphilic cyclodextrin systems.

With the aim of exploring relationships between the chemical structure and the physico-chemical properties of amphiphilic beta-cyclodextrin, a reappraisal of the obtaining of pure heptakis (2,3-di-O-hexanoyl)-beta-cyclodextrin (beta-CDC(6)) was undertaken. In this paper the chemical characterization of the newly synthesized beta-CDC(6) and its ability to form mixed structures with dimyristoylphosphatidylcholine (DMPC) are reported. Miscibility of the two amphiphiles is examined: (i) in monolayers formed at the air-water interface by analyzing the surface pressure-area isotherms; and (ii) in fully hydrated mixtures by differential scanning calorimetry (DSC) and X-ray diffraction at small and wide angles. Results demonstrate that the beta-cyclodextrin derivative is partially miscible to the phospholipid: intimate mixing occurs at beta-CDC(6) molar ratios smaller than 7-15 mol%, depending on the dimensional scale considered, while beyond these compositions phase separation is observed. At the air-water interface, the miscibility region of the two compounds shows non-ideal behavior characterized by the non-additivity of the molecular areas in the mixed monolayers. At the three-dimension level, the formation of a beta-CDC(6)/DMPC mixed lamellar phase occurs except at beta-CDC(6) molar ratios close to 5 mol% at which a highly ordered structure is depicted below the solid-to-liquid state transition of the DMPC hydrocarbon chains. At beta-CDC(6) contents higher than 7 mol%, the mixed assemblies coexist with excess amphiphilic cyclodextrin which then forms a separated hexagonal structure.

The effect of the type and the concentration of the lipophilic surfactant on the stability and release kinetics of the W/O/W multiple emulsions.

Stable multiple emulsions that contain different lipophilic surfactants in the internal aqueous phase have been formulated. The multiple systems were assessed by evaluating several parameters such as macroscopic aspect, droplet size, percent release and accelerated stability under centrifugation or elevated temperature. The effect of polymeric and monomeric surfactants on the release mechanism and stability was examined. An excess of monomeric surfactant in the oil phase enhances the release rate and decreases stability. The release rate can be decreased by an increase of the lipophilic surfactant concentration. It appears that the more the oil globule swells, the less hydrosoluble drug is released. As a result a high swelling capacity is associated with better stability.

W/O/W Multiple Emulsions Submitted to a Linear Shear Flow: Correlation between Fragmentation and Release.

The present work attempted to apply the theoretical framework described by Taylor to different multiple emulsions under shear. The results were in relatively good agreement with the theory. The correlation between the fragmentation and release studies was well proved. Moreover, these studies showed that mechanisms taking place during the breakup were complex and did not always lead to a total release of the entrapped electrolyte. Some phenomena such as a partial leakage of the internal aqueous compartment or the expulsion of aqueous microglobules covered by a residual lipophilic film were able to restrict the release. Copyright 1999 Academic Press.