THE FORMATION OF AN INCLUSION COMPLEX OF METHOCARBAMOL WITH HYDROXYPROPYL-BETA-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 characte rized 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 dissol ution rate. Host-guest interactions in aqueous solution were studied b y proton nuclear magnetic resonance spectroscopy (H-1-NMR) and in the solid state by differential scanning calorimetry (DSC) and infrared sp ectroscopy (IR). The stoichiometry of the isolated complex was determi ned by reversed phase high pressure liquid chromatography (RP-HPLC), L H-NMR spectroscopy and elemental analysis. The solubility and dissolut ion rate of ML in free and complexed form were examined in aqueous sol ution. The stability constant of the complex was determined by the cla ssical solubility techniques. The chemical stability of free and compl exed ML, in buffered solution at pH 7.4 and at two different temperatu res, 37 and 60 degrees C, was monitored using an HPLC method and resul ted in a 2-fold increase in the stability of complexed ML compared to free ML. (C) 1997 Elsevier Science B.V.