LONG-ACTING INJECTABLE OXYTETRACYCLINE-LIPOSPHERE FORMULATIONS

Oxytetracycline (OTC) was encapsulated in a liposphere delivery system composed of OTC, solid triglyceride, phospholipid, buffer solution and preservatives. The formulation is an injectable microdispersion containing 8-20 wt% OTC with an average particle of size of 30 mu m. The in vitro t(1/2) release of OTC was in the range of 28 h. Serum OTC concentration after a single intramuscular injection of OTC-liposphere formulation in turkeys showed an effective extended release for 3-5 days as compared to about 1 day for the commercial OTC solution (Dabicycline, 10 wt% in acidic solution). A mixture of OTC in lipospheres and OTC solution in a 4:3 volume ratio resulted in initial high OTC serum levels that lasted for 5 days. The biodegradability of the formulation was demonstrated by observing the injection site for up to 28 days after injection. The blank formulation was readily eliminated from the site and no signs of residuals were observed 28 days after injection. OTC loaded formulations based on trilaurin were also degraded but at slower rate than the blank formulation that might be a result of the hydrophobicity of OTC which retards hydrolysis and biological elimination.