The objective of this work was to assess the in vitro characteristics, in vivo pharmacokinetics and in vivo pharmacodynamics of nalbuphine propionate (NAP)-loaded microspheres. An oil-in-water solvent evaporation method was used to incorporate NAP into poly (d,l-lactide-co-glycolide) (PLGA)-based microspheres. 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 ∼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 pharmacokinetic studies after subcutaneous injection of NAP-loaded microsphere showed a sustained plasma nalbuphine (NA)-time profile, with 100% relative bioavailability comparing to the AUC obtained after intravenous injection. The in vitro release pattern correlated well with the in vivo pharmacokinetic profile. The pharmacodynamic studies evaluated using paw pressure model also showed a prolonged pharmacological response after injection of microspheres. A linear correlation between the percent analgesic effect and the logarithm of plasma NA concentration was obtained, suggesting the pharmacological response can be reflected by plasma drug concentration. This correlation may be utilized for evaluating the pharmacological responses of various NA and its prodrug-based formulations with known plasma NA concentrations.
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