Effect of cyclodextrins on the degradation rate of benzylpenicillin

The effect of cyclodextrin (CD) inclusion complexes on the degradation of benzylpenicillin in aqueous solutions was investigated at several different pH values and 37°C. The effects of neutral as well as both positively and negatively charged CDs were evaluated; all together 13 different CDs. Kinetic studies with HPβCD and RMβCD at pH ranging from 1.2 to 9.6 showed that CDs have stabilizing effect on the β-lactam ring in aqueous acidic media but generally accelerated the hydrolytic cleavage of the β-lactam ring in neutral and basic media. At physiologic pH (pH 7.4) quaternary ammonium CD derivatives (i.e., positively charged CD derivatives) have the highest catalytic effect, resulting in 6- to 18-fold enhancement of hydrolysis rate, while both the neutral methylated CDs had much less effect, resulting in 2- to 3-fold enhancement, and the negatively charged CD derivatives, resulting in only about 1.1- to 1.2-fold enhancement in the hydrolytic cleavage of the β-lactam ring. Addition of water-soluble polymers to the aqueous reaction media containing CDs was shown to decrease the catalyzing effects of CDs on the β-lactam hydrolysis.