Crystalline Modifications of Ampicillin I: the Trihydrate

Abstract

WE report the existence of the zwitterionic form of 6-[D(−)α-aminophenylacetamido] penicillanic acid (I; ampicillin) in the crystalline trihydrate. The synthesis of ampicillin and of related acid stable α-substituted benzyl-penicillins has been reported by Doyle et al.¹. Ampicillin has been shown to crystallize in two forms depending on the temperature of the aqueous solution from which crystallization is initiated². The anhydrous modification is obtained by crystallization from an aqueous solution at temperatures above 60° C, whereas the trihydrate is obtained from aqueous solutions at temperatures below 50° C. The various forms of ampicillin can easily be distinguished by their infrared spectra in the solid state. Austin, Marshall and Smith² conclude from a study of the infrared spectra of the various forms of crystalline ampicillin that the only two modifications are the anhydrate and the trihydrate and that the other hydrates that have been reported are either amorphous or partially dehydrated trihydrate.