Development of a chitosan-derivative micellar formulation to improve celecoxib solubility and bioavailability

Abstract

Context: Celecoxib is an anti-inflammatory drug, specific inhibitor of COX-2, classified as a BCS class II compound due to its very low aqueous solubility (3 μg/mL) and good permeability.

Objective: An innovative micellar formulation of celecoxib has been developed to increase its solubility and, consequently, its oral bioavailability.

Materials and methods: Quaternary-ammonium-palmitoyl-glycol-chitosan (GCPQ) was selected as carrier, due to its micelle-forming ability joined to its solubilizing and enhancer properties towards hydrophobic drugs. A Doehlert design was applied to optimize the drug solubilizing efficiency of the micellar formulation. Tested factors were GCPQ concentration and time and power of probe sonication during micelles formation; the response to maximize was the celecoxib solubility.

Results: The response-surface study allowed a thorough investigation of the effect of factors variations on the response over the considered experimental domain and identification of the best variable combination in order to maximize the desired improvement in drug solubility. The optimized micellar formulation (GCPQ 4.5 mg/mL; 25 min at 60% power of probe sonication) enabled an about 60-fold increase in celecoxib aqueous solubility. The optimized formulation, tested in vivo in mice by the writhing test, allowed a statistically significant shortening (p < 0.05) of the pain alleviation onset and a more intense effect (p < 0.05) with respect to the celecoxib aqueous suspension obtained by the commercial formulation.

Conclusions: The results proved that the developed GCPQ micellar formulation is a valuable approach for improving the therapeutic effectiveness of celecoxib.

• Amphiphilic quaternized chitosan
• micellar systems
• solubility improvement
• statistical design of experiments
• writhing test