Stability of solid dosage forms. I. Hydrolysis of meclofenoxate hydrochloride in the solid state.

Abstract

The kinetics of hydrolysis of mechlofenoxate hydrochloride (MF-HCl) into p-chloro-phenoxyacetic acid (CPA) and dimethylaminoethanol hydrochloride (DMAE-HCl) in the solid state were studied with respect to the effect of temperature (50 to 80°C) and humidity (20 to 80%RH). The degradation ratio, χ at the initial stage could be correlated to time by the equation χ=ktn where k and n are parameters. The degradation at the later stage was found to conform to first-order kinetics. The following mechanism is proposed : at a humidity below the CRH of MF-HCl, water vapor initiates the hydrolysis of MF-HCl into CPA and DMAEHCl on the surface of the solid by a gas-solid reaction. Once DMAE-HCl is produced, water starts to be adsorbed and forms a sorbed moisture layer, in which intact MF-HCl dissolves, diffuses and decomposes. After being completely dissolved, MF-HCl decomposes in an apparent first-order reaction. At a humidity above CRH, on the other hand, water is adsorbed rapidly on the surface of the solid and MF-HCl appears to decompose in solution from the beginning. The decomposition is not a first-order reaction because of the incompleteness of the dissolution and diffusion at the initial stage, but becomes first-order at the later stage.