Fentanyl-loaded poly(L-lactide-co-glycolide) microspheres for local anesthesia

Fentanyl-loaded biodegradable poly(L-lactide-co-glycolide) (PLGA) microspheres (MSs) were prepared to study the possibility for long-acting local anesthesia. We developed the fentanyl citrate (FC, highly water-soluble), and fentanyl base (FB, slightly water-soluble)-loaded PLGA (75:25 by mole ratio of lactide to glycolide) MSs by means of novel W'/O/O and conventional O/W methods, respectively. The influence of several preparation parameters, such as emulsifier types and concentrations, molecular weights and concentrations of PLGA, initial drug loading, etc., has been observed in the release pattern of fentanyl. The release of FC and FB in in vitro was more prolonged over 15 and 30 days, respectively, with close to zero-order pattern by controlling the preparation parameters. Mechanisms of the release pattern of fentanyl-loaded PLGA MSs were discussed.