RESEARCH CONCERNING THE DEVELOPMENT OF A STABLE,
FIXED COMBINATION OF ASPIRINE, PARACETAMOL, CAFFEINE
AND AN ANTIALERGIC COMPONENT
VICTOR VOICU1, CONSTANTIN MIRCIOIU2, VALENTINA ANUȚA3*, LOREDANA ANDREEA VONICA4, ION MIRCIOIU4
1Department of Clinical Pharmacology and Toxicology, Faculty of Medicine, “Carol Davila” University of Medicine and
Pharmacy, Bucharest, Romania
2Doctoral School, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
3Department of Physical Chemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy,
Bucharest, Romania
4Department of Research and Development, Polisano Pharmaceuticals, Sibiu, Romania
*corresponding author: vali_anuta@yahoo.com
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Abstract:
The multitude of analgesic combinations based on the synergic effect of acetylsalicylic acid, paracetamol and caffeine have
in common the problem of irritative adverse effects and relative low stability. Addition of chlorpheniramine to this classical
combination allowed the reduction of the usual dosage and consequently of the gastrointestinal adverse effects. The present
paper aims to evaluate the stability of the quaternary combination, in both powder and tablet form. A preliminary study was
performed in order to evaluate the stability of all combinations of components as well as the compatibility of the active
pharmaceutical ingredients with different tableting excipients. The results allowed the development at industrial scale of a
new formulation containing 125 mg acetylsalicylic acid, 75 mg acetaminophen, 15 mg caffeine and 2 mg chlorpheniramine
combination. Further studies concerning the evaluation of the stability of the selected formula under International Conference
on Harmonization accelerated, intermediate and real-time storage conditions (over 36 months) put in evidence that
acetylsalicylic acid is the only component that presented a significant concentration decrease. Time to decreasing of
acetylsalicylic acid content to 90% was found to be 41 months.

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