Celecoxib - Spring and Parachute Approach

Celecoxib is a COX-2 inhibitor marketed by Pfizer as Celebrex to treat pain of osteoarthritis. The compound is poorly soluble in aqueous media. Although the compound is fairly well absorbed when administered orally, the poor solubility translates into modest bioavailability in animals [48]. Traditionally, salt forms of compounds with poor 

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 . 

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