Interaction of ibuprofen and indomethacin with caffeine

The potentiality of interaction of ibuprofen and indomethacin with caffeine was investigated by UV and IR spectrophotometry. Differential UV spectrophotometry revealed a decrease in optical intensity of the two drugs in presence of caffeine as well as a bathochromic shift in the delta max of ibuprofen. On the other hand, IR spectrophotometry confirmed such an interaction as evidenced by a marked change in the spectra of the two drugs in presence of caffeine. The stoichiometry of interaction of the two drugs with caffeine was determined and found to be 2:1. The stability constants of the complexes were determined and the complex of ibuprofen was found to be more stable. The complexes were prepared by the kneading method and the implication of interaction on certain pharmaceutical properties of the two drugs was monitored. These included apparent solubility in water, dissolution rate, stability, partitioning properties as well as dermal diffusion. The results depicted an increase in the apparent solubility of the two drugs in water, enhancement in their dissolution properties, increase in stability, decrease in their partition coefficients between phosphate buffer (pH = 5.5) and n-octanol as well as decrease in their release rate constants through abdominal rat skin. The latter result would point out to the limitation of using these complexes in transdermal systems.