Inverse targeting of diclofenac sodium to reticuloendothelial system-rich organs by sphere-in-oil-in-water (s/o/w) multiple emulsion containing poloxamer 403.

摘要

Sphere-in-oil-in-water (s/o/w) multiple emulsions containing diclofenac sodium were prepared by gelatinization of inner aqueous phase. A further modified version (s/o/wp) of s/o/w was formulated by adding 5.0% w/v poloxamer 403 to the external aqueous phase during the second step of emulsification in order to affect the adsorptive coating on the surface (s/o/wp). The inverse targeting of reticuloendothelial system (RES) rich organs was compared with a non reticuloendothelial system after intravenous administration of s/o/w multiple emulsion (treatment I) and poloxamer containing s/o/wp multiple emulsion (treatment II). The amount of diclofenac sodium in the plasma and various organs was measured to elucidate the effect of inverse targeting to RES and targeting to other tissues in terms of the incorporated drug. After i.v. administration, the half life (34.65 vs.16.26?h) and apparent volume of distribution of diclofenac sodium (2815 vs. 1671.5?ml/kg) were significantly higher in treatment II than in treatment I. It is concluded that the amount of drug in RES rich organs (spleen, liver) were significantly lower than the values in non-RES organs such as lungs, inflammatory tissue (synovial fluid) in treatment II than in treatment I.