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The stability of misoprostol oil is significantly improved in a hydroxypropyl methylcellulose (HPMC) dispersion (1:100). In order to assess the effect of water on misoprostol stability, the rate of misoprostol degradation was investigated in the misoprostol/HPMC dispersion at 55 degrees C, along with the water sorption isotherm, under seven different relative humidity (RH) conditions ranging from 0 to 81%. The results indicated that the first-order rate constants of misoprostol degradation increased in a concave-up fashion as the water content of the dispersion increased. Below 30% relative humidity (approximately 2% water), the first-order rate constants of misoprostol degradation were found to be minimum. The results of the stability study were interpreted in terms of the changing structure of HPMC as it related to the mobility of water and misoprostol within the HPMC dispersion.

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The characterization and measurement of the benzodiazepine and ethanol interaction has been of major interest for many years. Various pharmacological and biochemical studies have been employed to investigate this interaction, which is believed to occur predominantly in the CNS, but localization of one particular brain area has not been investigated. This research employed the rat cerebellum as a site to study the diazepam/ethanol interaction. The measurement of cerebellar ethanol and diazepam, by gas chromatography, demonstrated an enhancement of diazepam levels by ethanol. Ethanol and diazepam, alone and in combination, displayed a significant depression of cerebellar 3',5'-Guanosine Cyclic Monophosphate (cGMP). The depression seen by the combination was significantly greater than the simple algebraic sum, but insignificantly different from the corrected algebraic sum. The double reciprocal plot of the data demonstrated a common ordinate intercept for the diazepam line and the diazepam/ethanol (2 g/kg) line, thus indicating a competitive mechanism of action.