SIMULTANEOUS DETERMINATION OF KETOPROFEN AND ACETAMINOPHEN IN FIXED-DOSE COMBINATION FORMULATIONS BY FIRST-ORDER DERIVATIVE SPECTROSCOPY: APPLICATION TO DISSOLUTION STUDIES

  • JosÉ RaÚl Medina Departamento Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, México
  • Claudia Alejandra GarcÍa
  • Marcela Hurtado
  • Adriana Miriam DomÍnguez-ramÍrez

Abstract

Objective: To develop and validate a new and easy zero-crossing derivative method for the simultaneous determination of ketoprofen and acetaminophen in fixed-dose combination formulations and to demonstrate its application in dissolution studies.

Methods: Measurement was achieved using the first derivative signals at 243.2 nm for ketoprofen and at 260.5 nm for acetaminophen. The method was validated according to ICH guidelines. The proposed method was applied for the simultaneous quantification of both drugs in samples taken during the study of dissolution profiles (USP Apparatus 2, 75 rpm and 900 ml of 0.1 M phosphate buffer pH 7.4) of Bifebral® reference product (100/300 mg ketoprofen and acetaminophen, respectively). Samples were also analyzed by a previously validated HPLC-PDA method. Dissolution profiles were compared by similarity factor f2. Additionally values of: t50%, t85%, dissolution efficiency and mean dissolution time, obtained for ketoprofen and acetaminophen using UV and HPLC-PDA methods, were compared by Student’s t-test.

Results: The first derivative spectrophotometric method was linear in the range of 25–200 µg/ml for ketoprofen and 25–150 µg/ml for acetaminophen (R2>0.99, *P<0.05). The within-day and between-day precision and accuracy were within the acceptable criteria (RSD<3.4% and 100±3%). Similarity factor f2 was 85.85 and 88.49 for ketoprofen and acetaminophen, respectively. No significant differences between data obtained with UV and HPLC-PDA methods were found (*P>0.05).

Conclusion: The proposed method can be used for the simultaneous determination of ketoprofen and acetaminophen, from fixed-dose combination formulations, in dissolution studies. The method is rapid, simple, accurate, and precise without the need of high-cost investment.

Keywords: Ketoprofen, Acetaminophen, Derivative spectroscopy, Zero-crossing method, Dissolution studies.

 

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References

1. Akural EI, Järvimäki V, Länsineva A, Niinimaa A, Alahuhta S. Effects of combination treatment with ketoprofen 100 mg+acetaminophen 1000 mg on postoperative dental pain: a single-dose, 10-hour, randomized, double-blind, active and placebo-controlled clinical trial. Clin Ther 2009;31:560−8.
2. Kalantzi L, Reppas C, Dressman JB, Amidon GL, Junginger HE, Midha KK, et al. Biowaiver monographs for immediate release solid oral dosage forms: acetaminophen (paracetamol). J Pharm Sci 2006;95:4−14.
3. Hiller A, Meretoja OA, Korpela R, Piiparinen S, Taiveinen T. The analgesic efficacy of acetaminophen, ketoprofen, or their combination for pediatric surgical patients having soft tissue or orthopedic procedures. Anesth Analg 2006;102:1365−71.
4. Salonen A, Silvola J, Kokki H. Does 1 or 2 g paracetamol added to ketoprofen enhance analgesia in adult tonsillectomy patients? Acta Anaesthesiol Scand 2009;53:1200−6.
5. Hyllestered M, Jones S, Pedersen JL, Kehlet H. Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review. Br J Anesth 2002;88:199−214.
6. Ong CKS, Seymour RA, Lirk P, Merry AF. Combining paracetamol (acetaminophen) with nonsteroidal anti-inflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg 2010;110:1170−9.
7. United States Pharmacopeia and National Formulary USP 38-NF 33; The United States Pharmacopeial Convention, Inc. Rockville, MD; 2015.
8. Farmacopea de los Estados Unidos Mexicanos 11a. Edición; 2014.
9. Karpińska J. Derivative spectrophotometry−recent applications and directions of developments. Talanta 2004;64:801−22.
10. El-Sayed AY, El-Salem NA. Recent developments of derivative spectrophotometry and their analytical applications. Anal Sci 2005;21:595−614.
11. Sánchez F, Bosch C. Recent development in derivative ultraviolet/visible absorption spectrophotometry: 2004−2008. Anal Chim Acta 2009;635:22−44.
12. Bosch C, Sánchez F. Recent applications in derivative ultraviolet/visible absorption spectrophotometry: 2009−2011. Microchem J 2013;106:1−16.
13. Listado de Medicamentos de Referencia. Cofepris. México. Available from: URL: http://www.cofepris.gob.mx/AS/ Documents/RegistroSanitarioMedicamentos/Rel_med_de_ref_15-08-2013.pdf. [Last accessed on 27 Oct 2015].
14. ICH, Q2B Validation of Analytical Procedures: Methodology, International Conference on Harmonization; 1996. Available from: URL: http://www.fda.gov/downloads/drugs/ guidance-complianceregulatoryinformation/guidances/ucm073384.pdf. [Last accessed on 24 Oct 2015].
15. Moore JW, Flanner HH. A mathematical comparison of dissolution profiles. Pharm Technol 1996;20:64−74.
16. Yuksel N, Kanik AE, Baykara T. Comparison of in vitro dissolution profiles by ANOVA-based, model-dependent and independent-methods. Int J Pharm 2000;209:57−67.
17. Anderson NH, Bauer M, Boussac N, Khan-Malek R, Munden P, Sardaro M. An evaluation of fit factors and dissolution efficiency for the comparison of in vitro dissolution profiles. J Pharm Biomed Anal 1998;17:811−22.
18. Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DD Solver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J 2010;12:263−71.
19. ICH, Q2(R1) Validation of Analytical Procedures: Text and Methodology, International Conference on Harmonization; 2005. Available from: URL: http://www.ich.org/fileadmin/ Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf. [Last accessed on 24 Oct 2015].
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Medina, J. R., GarcÍaC. A., M. Hurtado, and DomÍnguez-ramÍrezA. M. “SIMULTANEOUS DETERMINATION OF KETOPROFEN AND ACETAMINOPHEN IN FIXED-DOSE COMBINATION FORMULATIONS BY FIRST-ORDER DERIVATIVE SPECTROSCOPY: APPLICATION TO DISSOLUTION STUDIES”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 8, no. 2, Feb. 2016, pp. 244-8, https://innovareacademics.in/journals/index.php/ijpps/article/view/10044.
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