Dendimer-Mediated Solubilization, Formulation Development and in Vitro-in Vivo Assessment of Piroxicam

The present investigation was aimed at exploring dendrimer-mediated solubilization and formulation development followed by in vitro, in vivo assessment of piroxicam (PXM) nanocomposite. For this, two dendrimer generations (3.0G and 4.0G) were synthesized and characterized by IR, H-1 NMR spectroscopic and electron microscopy techniques. The optimized formulations containing 0.2% w/v of PXM loaded PAMAM dendrimer at pH 7.4 referred to as 0.2-D3P7.4 (3.0G) and 0.2-D4P7.4 (4.0G) resulted in significant enhancements of PXM solubility approximately by 107- and 222-fold, respectively. The in vitro release behavior of PXM from the formulation in medium-1 (PBS 7.4) and medium-II (PBS with 1 % albumin) and stability studies were also favorable. Pharmacokinetic study showed higher area under curve (AUC(0-t); mu g/mL/h) of 293.78 +/- 2.04 and 321.54 +/- 2.37 with optimized 0.2-D3P7.4 and 0.2-D4P7.4 formulations, respectively, as opposed to 279.11 +/- 1.48 with plain PXM. The elimination half-life of the drug encapsulated in the formulation was significantly higher (0.2-D3P7.4, 36.6 and 0.2-D4P7.4, 41.1; h) than that of pure drug (33.7 h; p < 0.005), and the overall elimination rate constant of formulations was also less as compared to free drug (p < 0.005). Pharmacodynamic assessment by rat-paw model of 0.2-D3P7.4 and 0.2-D4P7.4 formulations displayed inhibition levels of 54.21 +/- 1.25% and 59.33 +/- 0.63%, respectively, which are higher than those of plain PXM (41.81 +/- 2.9) formulations, after the sixth hour of administration. The second, fourth and eighth hour organ distribution data showed significantly higher recovery of PXM in rat paw with dendrimer-based formulations in comparison to plain PXM. However, comparison of overall data suggested 4.0G-based formulations to be superior to 3.0G as well as pure PXM.