A novel self emulsifying parenteral drug delivery system.
The application of three polyhydroxy alcohols for improving parenteral emulsion formulations was investigated. A mixture of lecithin, as the primary emulsifier, and Span 20 as the secondary emulsifier, was used as the emulsifier system. The polyhydroxy alcohols selected were glycerol, propylene glycol and sorbitol. Soybean oil-in-water emulsions were prepared with the addition of increasing concentrations of each polyhydroxy alcohol. It was found that anhydrous mixtures of oil, surfactants and 30% or higher concentration of glycerol formed self emulsifying isotropic liquids, suitable for preparing Parenteral Self Emulsifying Drug Delivery Systems (PSEDDS). Spontaneous emulsification to submicron particle size of 0.4 micron occurred when these isotropic liquids were gently mixed with water. A PSEDDS formulation, containing 0.5% lidocaine, as the model drug showed similar spontaneous emulsification with particle size of 0.39 micron. Formulations containing propylene glycol, or sorbitol or lower concentrations of glycerol did not form self emulsifying mixtures. There were substantial differences in the particle size reduction pattern with each polyhydroxy alcohol. Glycerol was most effective, with minimum particle size obtained at 30% concentration. Addition of propylene glycol resulted in minimum particle size at 60% concentration. But there was increase in particle size at higher concentrations. Sorbitol was not very effective in reducing particle size. Alteration of the surfactant phase distribution at the interface was found to be the primary effect of polyhydroxy alcohols.
Krishna
G
G
Vion Pharmaceuticals Inc., New Haven, CT 06511, USA.
Sheth
B B
BB
D016503:Drug Delivery Systems; D004655:Emulsions; D005079:Excipients; D007263:Infusions, Parenteral; D013501:Surface-Active Agents
D004655:Emulsions; D005079:Excipients; D013501:Surface-Active Agents