Solid-state emulsions

Solid-state emulsions are solids that self-emulsify into a liquid system upon contact with an aqueous phase. Depending on the materials and processing utilized, 0/W or W/O/W emulsions may be fabricated (Myers and Shively, 1992). The ability to store these systems as solids and to reconstitute them when needed for administration is attractive. Since the rationale for delivering proteins and peptides by multiple emulsions has been shown and the long-term stability of aqueous W/O/W systems is not critical, the majority of the work in the area of solid-state emulsions has focused on the solid-state stability of these systems. The physical properties 

Solid-state emulsions are prepared using similar techniques (Chiou and Reigelman, 1971) to those used to prepare solid-state dispersions (suspensions), hence the name (Shively, 1993a). As for conventional multiple emulsions, a primary (W/0) emulsion is prepared (Myers and Shively, 

The same opportunities therefore exist to custom-tailor the contents of the interior aqueous phase and oil phase to the particular requirements of the protein. An aliquot of the primary emulsion is added to a rotary vacuum flask. Sucrose, or another suitable lattice material, is dissolved in sufficient water and added to the flask. A typical ratio of sucrose to primary emulsion is 3 1 (sucrose primary emulsion, w/w). Vacuum is applied until a brittle foam is produced. 

The resulting solid (or foam) is stored at a temperature below the glass-transition temperature of sucrose in a desiccator until required (Shively and Myers, 1993). The effects of excipients on aging (Myers and Shively, 

process and storage conditions (Shively and Myers, 1993), and the particle size (Shively, 1993a,b) have also been reported. The addition of buffer to the prepared solid-state emulsion results in a significant majority of single internal aqueous droplets within an oil membrane (Myers and Shively, 992). 

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Changes in crystallinity during storage of solid-state emulsions from which oil-in-water emulsions are prepared was reported.731... 

M. L. Shively and S. Myers, Solid-state emulsions The effects of process and storage conditions, Pharm. Res. 10, 1071-1075(1993). 

Oral Administration of Vancomycin Solid-state Emulsion... 

F nre 2. Serum concentrations of vancomycin in conscious rats following administration of vancomycin within W/O/W solid-state emulsion. A 50-mg/kg dose of a vancomycin solid-state emulsion formulation was orally administered to rats. Serum levels of vancomycin were measured immediately prior to administration (r = 0) and 0.5, 1,2,3,4, 5,6,8, 10, 12, 24, and 36hr after administratioiL Data represent the mean SEM obtained in 3 animals. Sensitivity limit of assay was 2.0pg/ml (95% confidence greater than zero). Rats orally admirtistered the eqiuvalent dose of the cotrtmereial oral product resulted in no detectable semm levels (data not shown). (After Shively and Thompson, 1995.)... 

Multiple emulsions are unique in that a true liquid phase is maintained separate from an external aqueous phase. This may be especially important for bioactive molecules that cannot be appropriately stabilized in the solid state. In addition, the separation of aqueous phases enables highly specialized environments, conducive to protein activity, to be prepared. The physical instability of conventional systems remains a major factor limiting their wider application. Attempts to improve the physical stability of the aqueous dispersions through interfacial complexation and the use of microemulsions are improving the short-term stability. As an alternative approach, solid-state emulsions attempt to store the multiple emulsion as a solid. Although solid-state emulsions appear to have the potential to be useful protein delivery systems, a substantial experimental data base has yet to be generated. 

Shively, M. L., 1993a, Characterization of oil-in-water emulsions prepared from solid-state emulsions Effect of matrix and oil phase, Pharm. Res. 10 1153-1156. 

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