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Non-aqueous or oil-in-oil emulsions may be used as reservoirs to deliver lipophilic or hydrolytically unstable drugs. Emulsions of castor oil-in-silicone oil (co/so) release drugs slowly in vitro. To investigate the potential use of such formulations as depot preparations in vivo, drug absorption and distribution from an intramuscular injection site to various organs in the rat was studied. 3H-dexamethasone (0.1 mg/kg) was incorporated into the castor oil (disperse phase) of co/so emulsions and in castor oil-in-water (co/w) emulsions, the latter serving as control. 3H-dexamethasone was absorbed after intramuscular injection of co/w emulsions, reaching a plasma Cmax of 0.078 μg/ml at 2.0 h (Tmax). For co/so emulsions, a lower Cmax (0.048 μg/ml) was observed with a longer Tmax (4.0 h). No significant difference was found between the two formulations in the area under the plasma concentration–time curve (AUC∞), or in clearance (CL). Administration of 3H-dexamethasone in the co/so emulsion improved the mean residence time (MRT) and the elimination half-life (t1/2) in comparison to the co/w emulsion. The clearance of 3H-dexamethasone from the co/so emulsions at the injection site was also slower and at 4.0 h post-injection the amount of drug remaining in the muscle was found to be eight times higher than with the co/w emulsions. For both formulations, a high uptake of 3H-dexamethasone was identified in the liver and kidneys whereas smaller amounts were found in other tissues. Non-aqueous emulsions could be considered as depot formulations for sustained release drug delivery, but further studies on the choice of the continuous phase are necessary to optimize effects.