Effect of cyclodextrins on the degradation rate of benzylpenicillin
Popielec, A.; Fenyvesi, É; Yannakopoulou, K.; Loftsson, T.
Die Pharmazie 71(2): 68-75
2016
ISSN/ISBN: 0031-7144 PMID: 27004370 Document Number: 686178
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.