Synthesis and Formulation of Several Epinephrine Salts as an Aerosol Dosage Form

Abstract

A satisfactory method for the preparation of various salts of epinephrine such as the maleate, malate, and fumarate was developed. Following the synthesis of these salts, a study of the partition coefficient of these salts in higher molecu1ephrine bitartrate in these same vehicles. The solubility of these new salts in chloroform, carbon tetrachloride, and fluorinated hydrocarbons was then determined. Several systems incorporating these new salts were prepared and subjected to a preliminary stability study. The partition coefficient of epinephrine maleate determined between octyl alcohol-water and hexadecyl alcohol-water was found to be higher than the value for epinephrine bitartrate, malate, and fumarate. The solubility of epinephrine maleate and fumarate in four propellants (dichlorodifluoromethane, dichlorotetrafluoroethane, monochlorodifluoroethane, and difluoroethane) was found to be slightly higher than the epinephrine bitartrate and malate. As expected, difluoroethane dissolved the highest amount of epinephrine salts as compared to the other propellants studied. Epinephrine maleate and bitartrate were found to have greater stability than the epinephrine malate and fumarate compounds on the basis of the preliminary stability study.