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Misoprostol dehydration kinetics in aqueous solution in the presence of hydroxypropyl methylcellulose
D Toledo-Velasquez1, H T Gaud, K A Connors
1School of Pharmacy, University of Wisconsin, Madison 53706.
Abstract:
Misoprostol (Searle), and 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 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.
Insights
Hydroxypropyl methylcellulose (HPMC) stabilizes misoprostol in aqueous solution by physically hindering water access, not through direct interactions. This polymer entanglement slows drug diffusion, offering a protective effect.
Area of Science:
- Physical chemistry
- Polymer science
- Pharmaceutical sciences
Background:
- Misoprostol, an E1-type prostaglandin, is stabilized in solid dispersion with hydroxypropyl methylcellulose (HPMC).
- Previous studies found no evidence of specific intermolecular interactions between misoprostol and HPMC.
- Understanding misoprostol's stabilization mechanisms is crucial for pharmaceutical formulation.
Purpose of the Study:
- To investigate the dehydration kinetics of misoprostol in aqueous solution.
- To determine the effect of hydroxypropyl methylcellulose (HPMC) on misoprostol's dehydration kinetics.
- To elucidate the mechanism of stabilization provided by HPMC.
Main Methods:
- Studied dehydration kinetics of misoprostol in aqueous solution at pH 7.66.
- Compared kinetics in the absence and presence of hydroxypropyl methylcellulose (HPMC).
- Analyzed kinetic data to infer the nature of misoprostol-HPMC interactions.
Main Results:
- Misoprostol dispersed with HPMC showed a small but significant stabilizing effect in pH 7.66 aqueous solution.
- No evidence of specific complex formation between misoprostol and HPMC was observed in solid or solution states.
- Kinetic data suggest HPMC limits water access to misoprostol.
Conclusions:
- Hydroxypropyl methylcellulose (HPMC) stabilizes misoprostol via physical hindrance of water, not direct intermolecular interactions.
- Entanglement of misoprostol within the HPMC polymer matrix limits water diffusion.
- Slow drug diffusion from the polymer environment explains the observed kinetic stabilization.