Celecoxib nanosuspension: single-step fabrication using a modified nanoprecipitation method and in vivo evaluation

Conventional nanoprecipitation process involves addition of water miscible organic solvent containing drug to an aqueous phase containing hydrophilic surfactants to yield drug nanosuspension. However, nanosuspensions obtained with conventional nanoprecipitation process have very low colloidal stability. The objective of the present investigation was to fabricate drug nanosuspensions with good colloidal stability using a modified nanoprecipitation method. Celecoxib, a hydrophobic anti-inflammatory agent with low oral bioavailability, was used as a model drug for this investigation. The conventional nanoprecipitation method did not result in the nanosizing of the celecoxib. Incorporation of surface active lipophiles such as Labrafil 1944 CS (oleolyl macrogol glycerides) along with hydrophilic surfactants during nanoprecipitation process could successfully nanosize the celecoxib. The particle size of the nanosuspensions was influenced by the various parameters of the nanoprecipitation process and also by the concentration of the lipophilic stabilizer. The celecoxib nanosuspension was characterized by transmission electron microscopy, differential scanning calorimetry, and X-ray diffraction. Saturation solubility of celecoxib was dramatically improved in pH 1.2 buffer when formulated as nanosuspensions. The celecoxib nanosuspesnsion showed significantly higher in vitro dissolution rate and in vivo anti-inflammatory activity as compared to that of celecoxib-marketed formulation.