In vitro availability of some salicylates from their caffeine complexes. Khalil SA, Moustafa MA, Ghaly GM, Gouda MW, Motawi MW. Investigation of some complexes formed in solution by caffeine. DSC study and phase diagrams calculation of binary systems of paracetamol. Phase diagrams and thermodynamic properties of binary systems of drugs. Mechanism of eutectic formation upon compaction and its effects on tablet properties. Behavior of some eutectic drug compositions under accelerated aging conditions. Complexation of acetaminophen with methyl xanthines. Contribution à l’étude des associations paracetamol–théophilline et paracétamol–caféine. Jeanjean B, Alberola S, Terol A, Sablon F. A comparison of the behavior of eutectic mixture of sulfathiazole and that of ordinary sulfathiazole in man. Studies on absorption of eutectic mixture. Caffeine in alleviating migraine headache painthree double-blind, randomized, placebo-controlled trials. Lipton RB, Stewart WF, Ryan RE, Saper J, Silberstein S, Sheftell F. Physicochemical investigation of paracetamol–caffeine solid mixtures. Tkachenko ML, Zhnyakina LE, Kosmyninn AS. The effect of caffeine on the pharmacokinetics of acetaminophen in man. Iqbal N, Ahmad B, Janbaz KH, Gilani AH, Niazi SK. The analgesic effects of caffeine in headache. Effect of caffeine on acetaminophen analgesia. Laska E, Sunshine A, Zighelboim I, Roure C, Marrero I, Wanderling J, Olson N. No compound formation is found in the three systems. The composition of the three eutectics formed is confirmed by the related Tamman’s triangles. The paracetamol–aspirin phase diagram reveals the formation of one eutectic. It is concluded that the paracetamol–caffeine and aspirin–caffeine systems are similar and exhibit two invariants, one eutectic and one metatectic. The three phase diagrams are determined using X-ray diffraction and the differential scanning calorimetry from the binary mixtures. We have reinvestigated the paracetamol–caffeine, aspirin–caffeine, and paracetamol–aspirin phase equilibria diagrams taking into account the polymorphism of caffeine, paracetamol, and aspirin. In this work, we focus on the combination of paracetamol, aspirin, and caffeine, which is highly effective for the treatment of migraine headache pain. At the eutectic composition, both components are in reduced particle size and well dispersed. For this purpose, the use of eutectic mixtures is well known in the pharmaceutical field. The formation of solid dispersion can improve their solubility, consequently their bioavailability.
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