Date of Award


Degree Type


Degree Name

Master of Science in Pharmaceutical Sciences


Interdepartmental Program


The solubility profiles for metharbital, butabarbital, thiopental and thiamylal were determined in ethanol- water solvent systems at 25 c, in an attempt to define an approximate correlation between therapeutic activity and various solubility relationships. The relative lipophilicity of a drug molecule is an important factor in the physical and chemical processes involved when the therapeutic agent is introduced into a biological system. Binary solvent mixtures aid in delineating the relative polarity, in terms of dielectric constants, of these drugs. Spectrophotometric and, where applicable, gravimetric analyses, were utilized to determine the concentration of drug, in mg./ml., in the 41 solvent systems ranging in composition from pure ethanol to pure water. The dielectric requirement (DR) of the barbiturates investigated, and those reported for barbital and vinbarbital, illustrated an approximate inverse relationship with the number of carbon atoms in the molecule. A similar correlation was found with the solubilities in pure water, and the ratios of the solubilities in ethanol and at the DR to the solubility in water. The therapeutic indices of duration of action and the period of time involved between administration of the drug and the time when the activity is first manifested increased as the relative polarity of these barbiturates declined. The duration of these pharmacological parameters were also found to increase with a corresponding reduction in the hydrophilic nature of this series of compounds.



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