METHOCARBAMOL DEGRADATION IN AQUEOUS-SOLUTION

The kinetics of the hydrolysis of methocarbamol to the corresponding diol guaifenesin in aqueous solution was studied. Methocarbamol was rather stable in acidic media but easily hydrolyzed in alkaline solution. The formation of an unknown compound, proved to be an isomer of methocarbamol [the 3-(2-methoxyphenoxy)-propanediol 2-carbamate] is involved. The amounts of methocarbamol and the two degradation products resulting from storage of methocarbamol in various buffer solutions over a pH range of 8.0 to 10.0 at 70-80 degrees C (ionic strength, 0.5 M), were followed as a function of time by a reversed-phase HPLC stability-indicating method to clarify the degradation pathway of methocarbamol in alkaline solutions. Analysis of the concentration-time profiles reveals that base-catalyzed methocarbamol hydrolysis proceeded mainly through the formation of its isomer. The observed degradation rates followed approximately pseudo-first-order kinetics at constant pH and temperature.