Effect of Lyophilization on Parenteral Emulsions

Abstract

The feasibility of preparing lyophilized anhydrous products, for reconstitution in to emulsion dosage forms was investigated. Stable soybean o/w emulsions were prepared using a mixture of lecithin and Spant® 20 as the emulsifiers. Two series of emulsions were prepared for this study, each containing a polyhydroxy alcohol as a cosurfactant for particle size reduction. Increasing concentrations of glycerol (10–30% w/w) were added to one group of emulsions and propylene glycol (20–60% w/w) was added to the second group of emulsions. All formulations were found to have good particle size stability. The emulsion formulation containing 30% glycerol could be successfully lyophilized into an anhydrous product. Reconstitution of this lyophilized product resulted in an emulsion essentially similar to the original emulsion prior to lyophilization. This is because the mixture of the oil phase and 30% w/w glycerol formed a self-emulsifying system. All other emulsion formulations were not suitable for lyophilization. These formulations cracked during lyophilization, separating into an upper oil layer and a lower layer of the continuous phase. The formation of an upper oil layer prevented complete drying of these emulsions. The particle size of these lyophilized emulsions, when reconstituted with the external phase was greater than the emulsion particle size prior to lyophilization. But the change in particle size was less with increasing concentrations of polyhydroxy alcohols. These results indicate that emulsions can be lyophilized to prepare a product suitable for reconstitution to a parenteral emulsion dosage form provided the formulation is designed to withstand temperature and phase changes during the lyophilization process.