Crystalline Modifications of Ampicillin

Abstract

SINCE the introduction in 1961 of 6[D(−)α-amino-phenyl-acetamido]penicillanic acid¹ (I; ampicillin), its synthesis, bacteriology, pharmacology, and clinical use as a broad-spectrum penicillin have been extensively reported. Recently, attention has been turned to the physical properties of the solid. Thus, Grant and Alburn² have distinguished between, a crystalline anhydrous form and a monohydrate, which differ in solid-state infra-red absorption spectra, density, solubility, and thermal stability. They make no mention, however, of the highly crystalline ampicillin trihydrate which may be obtained by crystallization from water³ or by treating acid addition salts in moist organic solvents with amines of high molecular weight⁴. We wish to report further details of the various solid forms of ampicillin, both anhydrous and hydrated, and the means whereby they may be inter-converted.