Dosage form characteristics of microsphere-in-oil emulsion. II. Examination of some factors affecting lymphotropicity.

The relation between the physico-chemical properties and lymphotropicity of microsphere-in-oil (S/O) emulsion was investigated in comparison with water-in-oil (W/O) emulsion and sesame oil without any pharmaceutical modification. S/O emulsion gave the best lymph node accumulation of tripalmitin (14C), used as an oil tracer, after intramuscular injection. W/O emulsion was next most effective. Increase of injection volume and massage of the injection site accelerated the lymphatic transport of S/O emulsion, suggesting that hydrostatic tissue pressure plays a role in lymphatic delivery. Sesame oil solution of tripalmitin (14C) injected without any pharmaceutical modification was not effectively transferred to the lymph nodes, but addition of surfactants to the oil resulted in an increased accumulation of tripalmitin (14C) in the lymph nodes. Measurements of surface and interfacial tension of various formulations revealed that addition of surfactants caused a marked decrease of interfacial tension against water, which would promote dispersion of the formulations into smaller oil droplets. Microscopic observations of the thigh muscle after intramuscular injection of various oil formulations revealed a correlation between their extent of dispersion and their lymphotropicity. These results suggst that S/O emulsions have physico-chemical properties suitable for effective lymphotropic transport.