Crystalline molecular complexes between poly(ethyleneglycol) (PEG) and small aromatic molecules have been known since the 1990s, and the crystal structure of the cox-2 inhibitor mavacoxib:(PEG 600) appears in a patent from 2006. The polymer maintains a helical structure similar to that of native PEG, and there is an H-bonding interaction between the mavacoxib sulfonamide and the PEG ether. Celecoxib and valdecoxib have now been found to form cocrystals with PEG as well. The cocrystals form from solution, or from solid mixtures of drug with PEG1k-20k at 40oC. The incorporation into cocrystals has large effects on the properties of PEG: 1) the cocrystals remain intact after days of suspension in water despite the high solubility of PEG; 2) the PEG signal becomes strong in the 13C-CP/MAS NMR spectrum and gains a long 1H-T1rho value; and 3) the melting point of each cocrystal is >40oC above that of PEG 3350.Cocrystals of mavacoxib, celecoxib and valdecoxib have now been prepared with the non-ionic surfactant PEG (40) stearate (PES), a stearic acid ester of PEG. The PES and PEG cocrystals are identical by powder x-ray, and the stearate group appears to behave as an amorphous defect within PES cocrystals based on both solid-state NMR data and melting point reduction. The lipid tail relaxes �100-fold faster than in crystalline stearic acid, the 1H-T1 of PES cocrystals is reduced by >50% relative to PEG analogues and the PES cocrystals melt 10-15oC lower than for PEG.

Crystalline complexes of aryl sulfonamide drugs with the non-ionic surfactant polyoxyethylene (40) stearate

248th National Meeting (2014)

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