Effect of β- and γ-cyclodextrins and their methylated derivatives on the degradation rate of benzylpenicillin

Benzylpenicillin is characterized by instability in aqueous media, low oral bioavailability, and short biological half-life. Since their degradation products can cause allergic reactions, β-lactam antibiotics are supplied as a powder for injection and require special precaution when stored and re-constituted in water. An efficient method for β-lactam stabilization in the aqueous environment could reduce allergic side effects and facilitate their handling. Previously we proposed that complexation with cyclodextrins (CDs) is a way to achieve this goal. The purpose of the present study was to investigate the effect of methylation of CD on the chemical stability of benzylpenicillin. Kinetic studies revealed that degree of methylation of the CD molecule determines whether the CD has destabilizing or stabilizing effect on the β-lactam. The fully methylated βCD derivative Trimeb stabilizes benzylpenicillin while partial methylation of βCD only decreases to some extent the catalytic effect of native βCD. The complexes of all investigated CDs were also studied by DSC, FT-IR and NMR spectroscopy.