Lipid nanocapsule-based gels for enhancement of transdermal delivery of ketorolac tromethamine

Abstract

Previous reports show ineffective transdermal delivery of ketorolac by nanostructured lipid carriers (NLCs). The aim of the present work was enhancement of transdermal delivery of ketorolac by another colloidal carriers, lipid nanocapsules (LNCs). LNCs were prepared by emulsification with phase transition method and mixed in a Carbomer 934P gel base with oleic acid or propylene glycol as penetration enhancers. Permeation studies were performed by Franz diffusion cell using excised rat abdominal skin. Aerosil-induced rat paw edema model was used to investigate the in vivo performance. LNCs containing polyethylene glycol hydroxyl stearate, lecithin in Labrafac as the oily phase, and dilution of the primary emulsion with 3.5-fold volume of cold water produced the optimized nanoparticles. The 1% Carbomer gel base containing 10% oleic acid loaded with nanoparticles enhanced and prolonged the anti-inflammatory effects of this drug to more than 12 h in Aerosil-induced rat paw edema model.

Figure 1

SEM micrographs of optimized formulation of Ketorolac loaded lipid nanocapsules (S₂₀O₂₅W_3.5L_3.25).

Figure 2

Ketorolac release profile from lipid nanocapsules with different formulations.

Figure 3

Anti-inflammatory activity (Inhibition %) of ketorolac on paw edema induced with Aerosil injection (0.1 mL of 2.5% w/w) in rats (control), after administration of transdermal gels of optimized ketorolac LNC (0.5% and 2%), the vehicle, and the gel containing 0.5 or 2% of free ketorolac. The formulation of the gels of ketorolac LNC contained (1% Carbomer gel base containing 10% oleic acid and 2% ketorolac loaded in optimized LNCs (S₂₀O₂₅W_3.5L_3.25) prepared by 20% polyethylene glycol hydroxyl stearate, 3.25% lecithin, 25% Labrafac as the oily phase, and cold water as much as 3.5-folds of the total volume of the primary emulsion).