Controlled release of nalbuphine propionate from biodegradable microspheres: in vitro and in vivo studies

The objective of this work was to assess the in vitro characteristics, in v ivo pharmacokinetics and in vivo pharmacodynamics of nalbuphine propionate (NAP)loaded microspheres. An oil-in-water solvent evaporation method was us ed to incorporate NAP into poly (d.l-lactide-co-glycolide) (PLGA)-based mic rospheres. The morphology of the microspheres were evaluated using scanning electron microscopy which showed a spherical shape with smooth surface. A prolonged in vitro drug release profile was observed. with similar to 71.1% of incorporated drug released in 96 h. The release profile fit well to the Baker and Lonsdale's spherical matrix model. suggesting the release of NAP from microspheres was consistent with a diffusion mechanism. The in vivo p harmacokinetic studies after subcutaneous injection of NAP-loaded microsphe re showed a sustained plasma nalbuphine (NA)-time profile, with 100% relati ve bioavailability comparing to the AUC obtained after intravenous injectio n. The in vitro release pattern correlated well with the in vivo pharmacoki netic profile. The pharmacodynamic studies evaluated using paw pressure mod el also showed a prolonged pharmacological response after injection of micr ospheres. A linear correlation between the percent analgesic effect and the logarithm of plasma NA concentration was obtained, suggesting the pharmaco logical response can be reflected by plasma drug concentration. This correl ation may be utilized for evaluating the pharmacological responses of vario us NA and its prodrug-based formulations: with known plasma NA concentratio ns. (C) 2001 Elsevier Science B.V. All rights reserved.