In vitro evaluation of the complexation of non-steroidal anti-inflammatory drugs with caffeine

Abstract

Abstract The complexation of five non-steroidal anti-inflammatory drugs (NSAIDs) with caffeine was evaluated. Mixtures were prepared by powder mixing, trituration in a mortar with a pestle and recrystallisation from a common solvent. The properties of the mixtures and the recrystallised materials, evaluated by differential scanning calorimetry (DSC) and dissolution rate measurements, differed significantly (P<0.05). Disappearance of peaks in DSC thermograms, or lowering of melting points of the NSAIDs in NSAID-caffeine co-precipitates were ascribed to the complexation of caffeine with the NSAIDs. The dissolution rate of ketoprofen was not affected by the addition of caffeine but the dissolution rates of ibuprofen, mefenamic acid, naproxen and indomethacin were significantly enhanced (P0.05) after being co-precipitated, or mixed in a mortar or V-blender, with caffeine. Higher dissolution rates, because of the complexation of caffeine and the drugs in solution, could translate into changed bioavailability and different pharmacokinetic parameters. Less gastrointestinal irritation and quicker onset of required blood levels might improve the efficacy of NSAIDs, a factor that, if confirmed, should be considered when prescribing these drugs to patients.