Pharmacodynamic/pharmacokinetic correlation of optimized ibuprofen nanosuspensions having enhanced anti-inflammatory and antinociceptive activity

Abstract

The main objective of this study was to evaluate the antinociceptive and anti-inflammatory activity of ibuprofen (IB) nanoformulations which were developed in our previous study and showed enhanced in-vitro dissolution rate compared with the marketed formulation. The in-vivo pharmacodynamic (PD) studies were performed in mice. The antinociceptive effect of the formulations was evaluated using the formalin test, whereas the anti-inflammatory activity was evaluated by measuring oedema caused by formalin test. The optimized formulation exhibited nanosized particles with rapid dissolution compared with IB in water and marketed product. The antinociceptive and anti-inflammatory activity of IB was significantly improved in optimized nanosuspension compared with other formulations. A good correlation was observed between the pharmacokinetic and PD data: nanosuspension > freeze-dried nanoparticles > marketed product > unhomogenized formulation > IB suspension in water. There was a significantly good correlation between percentage inhibition of paw oedema with peak serum concentration (Cmax) and time at which the Cmax is observed (Tmax) but not area under the curve (AUC), whereas there was a good correlation between percentage inhibition of formalin-induced nociception in phase II, but not phase I, with AUC and Cmax but not Tmax. The development of IB nanoformulation by ultra-homogenization technique improved its dissolution and PD properties.