Polyoxyethylene-polyoxypropylene block copolymer gels as sustained release vehicles for subcutaneous drug administration

Abstract

Polyoxyethylene-polyoxypropylene surface-active block copolymers (Pluronic®) were evaluated as a vehicle for subcutaneous administration of drugs using a phenolsulfophthalein (PR) as a tracer. The type of Pluronic® copolymer (F108 or F127), and their concentrations, and the effect of solutes (NaOH, NaCl or PR) on gelation properties were studied. Sodium hydroxide and sodium chloride decreased the gel-sol transition temperature, whereas the opposite effect was observed with PR. The ‘in vitro’ release rates obtained for PR were inversely proportional to the concentration of Pluronic used and a zero-order release rate was observed in all preparations assayed. Pluronic® F127/PR preparations were administered subcutaneously (SC) to Wistar rats and PR plasma levels were compared with those reached after SC or intravenous (i.v.) administration of a PR aqueous solution. The gel formulation produced a sustained plateau level within 15 min that lasted 8–9 h. In vivo data analysis was performed with the JANA and PCNONLIN computer programs. The best fittings for experimental data from Pluronic gels were obtained using a zero-order input and first-order output two-compartment model. The results obtained suggest that PF127 aqueous gels may be of practical use as a vehicle for SC administration of drugs.