DERIVATIVES OF THE RATIO SPECTRA FOR DETERMINATION OF ACETYLSALICYLIC ACID, ACETAMINOPHEN AND CAFFEINE IN FIXED-DOSE COMBINATION FORMULATIONS: APPLICATION TO DISSOLUTION STUDIES
Objective: To develop a ratio-derivative spectrophotometric method for the simultaneous quantification of acetilsalycilic acid (ASA), acetaminophen (ACE) and caffeine (CAF) in fixed-dose combination formulations. The proposed method was applied to the reference drug product Excedrin® in dissolution studies.
Methods: The method is based on the use of the first- and second- derivatives of the ratio spectra and measurement at zero-crossing wavelengths. Dissolution profiles of ASA, ACE and CAF were obtained following pharmacopeial conditions, USP Apparatus 2 at 100 rpm and 900 ml of water. Dissolution samples were treated with the proposed method and the results were compared with those obtained with a validated HPLC procedure. The dissolution efficiency was used to compare dissolution profiles (HPLC vs. UV-derivative method).
Results: The method was linear in the range of 5-25 µg/ml of ASA, 2.5-20 µg/ml of ACE and 1-8 µg/ml of CAF (R2 > 0.999, *P < 0.05). The precision and accuracy of synthetic mixtures were within the aceptable criteria (2.11-3.43% and 96.78-104.15%, respectively). Nitrocellulose filters were the best option to filter samples and stability of all drugs was adequate if solutions were stored at 4ºC during 24 h. No significant differences were found between dissolution profiles (*P < 0.05).
Conclusion: The proposed method allows the simultaneous determination of ASA, ACE and CAF commercial formulations. The method is simple, accurate and precise and can be used in dissolution studies. Spectrophotometric methods are of low cost and harmless to the environment and therefore a better alternative than chromatographic methods.
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