Drug release from injectable depots: two different in vitro mechanisms.

Certain poly (lactide-co-glycolide) (PLGA)/benzyl benzoate (BB) solutions can form gels when injected into buffer (depot formation) as well as upon ageing under ambient conditions. When evaluating various PLGAs in benzyl benzoate, we have found that only those that gel upon ageing also form gel depots in buffer. This indicates that depot formation in this system may be fundamentally different from the phase inversion depot formation that has been observed for PLGA in water-miscible solvents. The drug release kinetics in vitro is controlled both by diffusion and erosion, with the base form of the drug being always released faster than its salt form. This is due to base-catalyzed hydrolysis. While gel permeation chromatography (GPC) measurements show a continuous decrease in molecular weight, the rheological properties upon buffer injection show maxima, for the base drug and the salt drug. The location of the viscosity maximum with time is dependent on the nature of the drug and its concentration.