Comparative in vivo studies of aqueous solution, multiple w/o/w, and w/o emulsions showed that formulating 5-fluorouracil in emulsion systems sigdcantly sustained the release of the drug from intramuscular injection sites in the rat.
Intramuscular injection of the drug in both w/o and w/o/w emulsion systems produced sustained blood concentrations with a later blood level peak than observed following intramuscular injection of aqueous solutions of the drug. The multiple w/ o/ w emulsion exhibited a more rapid release of drug from the injection site than the w/o emulsion because of partitioning of the drug to the external aqueous phase during secondary emulsification.
The fate of the oil phase following intramuscular injection of a water/hexadecane/ water multiple emulsion spiked with l-'4C-hexadecane has been studied in rats as a function of stabilizer concentrations. Increasing the lipophilic surfactant (Span 80) concentration facilitated the clearance of the oily vehicle from the injection site, by mechanisms which remain to be elucidated.