The formation of an inclusion complex of methocarbamol with hydroxypropyl-β-cyclodextrin:: the effect on chemical stability, solubility and dissolution rate

The inclusion complex of the hydrophobic drug methocarbamol (ML) with hydroxypropyl-beta-cyclodextrin (HP beta CD) was prepared and characterized in the solid state and in aqueous solution. The prepared complex was studied by chromatographic, spectral and phase solubility methods to determine its structure, solubility, chemical stability and dissolution rate. Host-guest interactions in aqueous solution were studied by proton nuclear magnetic resonance spectroscopy (H-1-NMR) and in the solid state by differential scanning calorimetry (DSC) and infrared spectroscopy (IR). The stoichiometry of the isolated complex was determined by reversed phase high pressure liquid chromatography (RP-HPLC), LH-NMR spectroscopy and elemental analysis. The solubility and dissolution rate of ML in free and complexed form were examined in aqueous solution. The stability constant of the complex was determined by the classical solubility techniques. The chemical stability of free and complexed ML, in buffered solution at pH 7.4 and at two different temperatures, 37 and 60 degrees C, was monitored using an HPLC method and resulted in a 2-fold increase in the stability of complexed ML compared to free ML. (C) 1997 Elsevier Science B.V.