Interaction of glucocorticoids with xanthines

ABSTRACT

The potentiality of interaction of prednisone and prednisolone with xanthine derivatives, viz., caffeine, theophylline, dyphelline and acepifylline was investigated. Differential ultraviolet spectrophotometry revealed a marked effect of xanthines on the extinction coefficient of prednisone and prednisolone. The continuous variation method revealed the formation of 11 complexes between xanthine derivatives and prednisone or prednisolone with the exception of interaction between prednisone and acepifylline where two types of complexes 13 and 21 appear to be formed. Determination of the stability constant of the complexes revealed that theophylline and its derivatives acepifylline and dyphelline form more or less stable complexes with the two steroids compared to caffeine. The dissolution rate of the two steroids as well as their xanthine complexes was found to follow first order kinetics during the first 30 min of the dissolution run. On the other hand, the solubility power of theophylline and its derivatives is more or less higher than caffeine, this is more evident for prednisone. There is a lack of correlation between the solubility power of the complexing agents and the stability constant of the formed complexes, but there is a good correlation between the dissolution rate constant of prednisolone complexes and their stability constant [c.c. = 0.995]