Poly(ethyleneglycol) 500 Dimethylether as Novel Solvent for Injectable In Situ Forming Depots

Poly(D,L-lactide-co-glycolide) (PLGA) solutions in poly(ethyleneglycol)600 (PEG600), N-methyl-2-pyrrolidone (NMP) and poly(ethyleneglycol)500dimethylether (PEG500DME) as a novel solvent, were investigated as suitable for use in injectable in situ forming depots (ISFD). The hemolytic potential of the solvents was investigated. Viscosimetry was used to determine rheological properties of solvents and PLGA solutions. DSC was used to evaluate the stability of the PLGA solutions through investigation of the melting behavior of semicrystalline PEGs which depended on tempering and glass transition temperature of the PLGA. Phase separation was studied to determine ternary phase diagrams. In vitro release kinetics of the solvents and the surrogate methylene blue were investigated. Significantly less hemolysis was observed for PEG500DME compared to PEG600 and NMP. Newtonian fluid properties were found for all polymer solutions. A melting point depression of the solvents was detected in presence of PLGA. The duration of tempering of the polymer solutions showed no impact on their melting behavior. The initial in vitro release of methylene blue was according to the solvent diffusion kinetics. Low hemolytic potential, suitable viscosity for injection, stability of PLGA solutions in PEG500DME and the correlation between phase separation and in vitro release confirmed the potential of PEG500DME as a promising solvent for ISFD.