Comparative Study on Co-Ground Products of Rofecoxib with β-Cyclodextrin and Its Sulfobutyl Ether-7 Derivative in Solution and in the Solid State

The inclusion behavior of sulfobutyl ether-7 derivative ofβ-cyclodextrin (SBE7βCD), in solution and solidstate was compared with that of natural β-cyclodextrin(βCD) toward a poorly water-soluble anti-inflammatoryagent, rofecoxib (ROFX), chemically 44-(methylsulfonyl)phenyl]-3-phenyl-2 (5H)-furazone. Drug-cyclodextrin solidsystems were prepared by cogrinding in a ball mill. A phasesolubility method was used to evaluate the stoichiometries andstability constants of ROFX-βCD (1 : 1 and 62 M^-1)and ROFX-SBE7βCD (1 : 1 and 132 M^-1) complexes.The formation of inclusion complexes with βCD andSBE7βCD in the solid state were confirmed by infraredspectroscopy, differential scanning calorimetry, X-ray diffractometry,scanning electron microscopy and in the liquid state by phasesolubility analysis, nuclear magnetic resonance spectroscopy andcircular dichroism studies. Dissolution studies using the USP paddlemethod were carried out in phosphate buffer pH 7.2 at 37 °Cfor both βCD and SBE7βCD complexes of rofecoxib.Solubility enhancement was much greater for the rofecoxib-SBE7βCDcomplex compared to drug-βCD complex. The stability constantobtained for the SBE7βCD inclusion complex of rofecoxib wasthe highest. Finally, dissolution profiles obtained suggest thatSBE7βCD is more effective than β-cyclodextrin inimproving the pharmaceutical properties of rofecoxib.