Misoprostol Dehydration Kinetics in Aqueous Solution in the Presence of Hydroxypropyl Methylcellulose

Misoprostol (Searle), an E1-type prostaglandin, is known to be stabilized in the form of a solid dispersion with hydroxypropyl methylcellulose (HPMC), yet no evidence has been found for specific intermolecular interactions. In the present study, the dehydration kinetics of this prostaglandin were studied in aqueous solution in the absence and the presence of HPMC. The dispersion of the drug with HPMC, when dissolved in pH 7.66 aqueous solution, exerted a small but significant stabilizing effect. A possible interpretation of this kinetic result, together with lack of evidence for complex formation in both the solid and solution states, may be that HPMC exerts its stabilizing effect by physically limiting the access of water to the prostaglandin through an entanglement of the prostaglandin in the polymer environment, the diffusion of drug away from the polymer being slow on the time scale of the dehydration kinetics.