Parenteral water/oil emulsions containing hydrophilic compounds with enhanced in vivo retention: formulation, rheological characterisation and study of in vivo fate using whole body gamma-scintigraphy.

The preparation and characterization of parenteral water-in-oil (w/o) emulsions with a potential for sustained release of hydrophilic drugs was described with emphasis on rheological behaviour and spreading phenomenon after intramuscular (i.m.) injection in rabbit thigh muscle. Both steady state and dynamic rheological parameters were investigated showing Newtonian behaviour at low fraction of disperse phase ratio as opposed to viscoelastic and pseudoplastic behaviour at high fraction of disperse phase. Disappearance and spreading behaviour of hydrophilic radioactive markers, aprotinin (6512 g/mol) and pertechnetate (193 g/mol) entrapped in w/o emulsions from an i.m. injection site was studied by whole body gamma-scintigraphy. The retention of entrapped aprotinin 24 h postinjection was 83 +/- 5% for a low spreading emulsion and 76 +/- 6% for a high spreading emulsion. The corresponding values for pertechnetate were 50 +/- 11 and 23 +/- 2%, respectively. The relatively long retention times were suggested to be related to the good physical stability properties of the present emulsions. It was concluded that the presented w/o emulsions are promising vehicles for sustained release of hydrophilic drugs from an i.m. injection site.