Celecoxib formulation

Rapid form dissociation and precipitation of known forms of the parent celecoxib was observed in 0.1 N HCl, SGF, 0.02 N HCl, pH 6.5 phosphate buffer and pH 6.5 phosphate buffer with sodium dodecyl sulfate (SDS). The initial dissolution rate was found to be superior for the co-crystal versus the stable form of the parent compound, but rapid conversion to aggregated crystalline celecoxib made this co-crystal a poor candidate for direct use as a dosage form. This initial dissolution advantage was exploited further by formulating the co-crystal with PVP-K30 and the ionic surfactant SDS. Using this combination of excipients, the co-crystal was repeatedly observed to precipitate as a poorly crystalline mixture of metastable celecoxib form 4 and amorphous material. Although the co-crystal was not tested in vivo, the in vitro performance improvements are consistent with improvements observed in other celecoxib formulations with demonstrated in vivo advantages over Celebrex . 

The crystal structure of the cocrystal formed by celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-lH-pyrazol-l-yl]benzenesulfonamide) with nicotinamide has been solved from powder X-ray diffraction data [54], The dissolution and solubility of the cocrystal product were found to depend on the medium involved, and a number of the observed phenomena were shown to originate from differences in conversion of the cocrystal celecoxib polymorphic forms I and III. However, through the judicious use of choice excipients, a formulation was developed that took advantage of the crystalline conversion to be up to fourfold more bioavailable than the celecoxib Form-Ill marketed product. 

D. Screenivas Rao, M. K. Srinivasu, C. Lakshmi Narayana, and O. G. Reddy, LC separation of ortho and meta isomers of Celecoxib in bulk and formulations using a chiral column,/. Pharm. Biomed. Anal. 25 (2001), 21-30. 

Subramanian, N., Ray, S., Ghosal, S.K., Bhadra, R. and Moulik, S.P. (2004) Formulation design of self-microemulsifying drug delivery systems for improved oral bioavailability of celecoxib. Biol. Pharm. Bull, 27, 1993-1999. 

Guzmdn, H.R. Tawa, M. Zhang, Z. Ratanabanangkoon, P. Shaw, P. Gardner, C.R. Chen, H. Moreau, J.P. Almarsson, O. Remenar, J.F. Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations. J. Pharm. Sci. 2007, 96(10), 2686-2702. 

Celecoxib Low solubility, incomplete oral bioavailability, slow onset of action Celecoxib sodium and celecoxib nicotinamide salt or co-crystal plus formulation with improved dissolution profiles... 

Saha, R.N. Sajeev, C. Jadhav, P.R. Patil, S.P. Srinivasan, N. Determination of celecoxib in pharmaceutical formulations using UV spectrophotometry and liquid chromatography, J.Pharm.Biomed.Anal., 2002,28, 741-751. 

Ibrahim, M.M., et al. Natural bioadhesive biodegradable nanoparticles-based topical ophthalmic formulations for sustained celecoxib release. J. Pharm. Tech. Drug. Res. 2(1), 7 (2013)... 

SEDDS are particularly applicable for orally administered drugs, in soft or hard gelatin capsules that disintegrate in the gastrointestinal fluids (Sandri et al., 2010). Drugs with dissolution and bioavailability issues as fenofibrate (Soares et al., 2013), celecoxib (Fonte et al., 2011), or cyclosporine (Jin et al., 2011) have been formulated into SEDDS with success improvement of the oral controlled release of those drugs. 

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