Naproxen is one of the most used non-steroidal anti-inflammatory drugs (NSAIDs). It is used to treat pain of various origins, inflammation and fever. Pharmaceutical preparations containing naproxen are available with prescription and over-the-counter (OTC). Naproxen in pharmaceutical preparations is used in the form of acid and sodium salt. From the point of view of pharmaceutical analysis, it is crucial to distinguish between these two forms of drugs. There are many costly and laborious methods to do this. Therefore, new, faster, cheaper and, at the same time, simple-to-perform identification methods are sought. In the conducted studies, thermal methods such as thermogravimetry (TGA) supported by calculated differential thermal analysis (c-DTA) were proposed to identify the type of naproxen in commercially available pharmaceutical preparations. In addition, the thermal methods used were compared with pharmacopoeial methods for the identification of compounds, such as high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), UV-Vis spectrophotometry, and a simple colorimetric analyses. In addition, using nabumetone, a close structural analog of naproxen, the specificity of the TGA and c-DTA methods was assessed. Studies have shown that the thermal analyses used are effective and selective in distinguishing the form of naproxen in pharmaceutical preparations. This indicates the potential possibility of using TGA supported by c-DTA as an alternative method.

Department of Biophysics Faculty of Pharmaceutical Sciences in Sosnowiec Medical University of Silesia in Katowice Jedności 8 41 200 Sosnowiec Poland

Faculty of Mechatronics Informatics and Interdisciplinary Studies Technical University of Liberec 461 17 Liberec Czech Republic

Institute for Nanomaterials Advanced Technologies and Innovation Technical University of Liberec Stdentská 2 460 01 Liberec Czech Republic

See more in PubMed

Censi R., Rascioni R., Di Martino P. Changes in the solid state of anhydrous and hydrated forms sodium naproxen under different grinding and environmental conditions: Evidence of the formation of new hydrated forms. Eur. J. Pharm. Biopharm. 2015;92:192–203. doi: 10.1016/j.ejpb.2015.03.014. PubMed DOI

Janiec W. Farmakodynamika. PZWL; Warsaw, Poland: 2022.

Kyeremateng K., Troullos E., Paredes-Diaz A. Safety of naproxen compared with placebo, ibuprofen and acetaminophen: A pooled analysis of eight multiple-dose, short-term, randomized controlled studies. Curr. Med. Res. Opin. 2019;35:1671–1676. doi: 10.1080/03007995.2019.1612338. PubMed DOI

Weintraub W.S. Safety of non-steroidal anti-inflammatory drugs. Eur. Heart J. 2017;38:3293–3295. doi: 10.1093/eurheartj/ehx533. PubMed DOI

Swiss Pharmaceutical Socied . Index Nominum: International Drug Directory. 20th ed. MedPharm; Volkach, Germany: 2011.

Moyer S. Pharmacokinetics of Naproxen Sodium. Cephalalgia. 1986;6((Suppl. 4)):77–80. doi: 10.1177/03331024860060S409. PubMed DOI

Zejca A., Gorczyca M. Chemia Leków. PZWL; Warsaw, Poland: 2004.

Sevelius H., Runkel R., Segre E., Bloomfield S.S. Bioavilablity of naproxen sodium and its relationship to clinical analgesic effects. Br. J. Clin. Pharmacol. 1980;10:259–263. doi: 10.1111/j.1365-2125.1980.tb01753.x. PubMed DOI PMC

Zając M., Jelińska A. Ocena Jakości Substancji i Produktów Leczniczych. Karola Marcinkowskiego w Poznaniu; Poznań, Poland: 2010. Wydawnictwo Naukowe Uniwersytetu Medycznego im.

Polish Pharmaceutical Society . Polish Pharmacopoeia. 11th ed. Polish Pharmaceutical Society; Warsaw, Poland: 2017.

European Directorate for the Quality of Medicines & HealthCare . European Pharmacopoeia. 10th ed. EDQM; Strasbourg, France: 2021.

ICH . ICH Harmonised Tripartite Guideline: Validation of Analytical Procedures: Text and Methodology, Q2(R1) ICH; Geneva, Switzerland: 2005.

Holzgrabe U. Nuclear Magnetic Resonance Spectroscopy|Identification of Counterfeit Drugs and Herbal Medicine. In: Worsfold P., Poole C., Townshend A., Miró M., editors. Encyclopedia of Analytical Science. 3rd ed. Elsevier; Amsterdam, The Netherlands: 2019. pp. 182–185.

Parys W., Pyka-Pająk A. TLC-densitometry for determination of omeprazole in simple and combined pharmaceutical preparations. Pharmaceuticals. 2022;15:1016. doi: 10.3390/ph15081016. PubMed DOI PMC

Zapata F., López-Fernández A., Ortega-Ojeda F., Quintanilla G., García-Ruiz C. Introducing ATR-FTIR spectroscopy through analysis of acetaminophen drugs: Practical lessons for interdisciplinary and progressive learning for undergraduate students. J. Chem. Educ. 2021;98:2675–2686. doi: 10.1021/acs.jchemed.0c01231. PubMed DOI PMC

Jurásek B., Bartunek V., Huber Š., Fagan P., Vladimír Setnicka V., Králík F., Dehaen W., Svozil D., Kuchar M. Can X-ray powder diffraction be a suitable forensic method for illicit drug identification? Front. Chem. 2020;8:499. doi: 10.3389/fchem.2020.00499. PubMed DOI PMC

Amin M.O., Al-Hetlani E., Lednev I.K. Detection and identification of drug traces in latent fingermarks using Raman spectroscopy. Sci. Rep. 2022;12:3136. doi: 10.1038/s41598-022-07168-6. PubMed DOI PMC

Ramos P. Application of thermal analysis to evaluate pharmaceutical preparations containing theophylline. Pharmaceuticals. 2022;15:1268. doi: 10.3390/ph15101268. PubMed DOI PMC

Song J.S., Sohn Y.T. Crystal forms of naproxen. Arch. Pharm. Res. 2011;34:87–90. doi: 10.1007/s12272-011-0110-7. PubMed DOI

Guo W., Li C., Du P., Wang Y., Zhao S., Wang J., Yang C. Thermal properties of drug polymorphs: A case study with felod pine form I and form IV. J. Saudi Chem. Soc. 2020;24:474–483. doi: 10.1016/j.jscs.2020.04.003. DOI

Ramos P., Broncel M. Influence of storage conditions on the stability of gum arabic and tragacanth. Molecules. 2022;27:1510. doi: 10.3390/molecules27051510. PubMed DOI PMC

Sovizi M.R. Thermal behavior of drugs: Investigation on decomposition kinetic of naproxen and celecoxib. J. Therm. Anal. Calorim. 2010;102:285–289. doi: 10.1007/s10973-009-0668-1. DOI

Pitucha M., Ramos P., Wojtunik-Kulesza K., Głogowska A., Stefańska J., Kowalczuk D., Drózd M., Augustynowicz-Kopeć E. Thermal analysis, antimicrobial and antioxidant studies of thiosemicarbazone derivatives. J. Therm. Anal. Calorim. 2023;148:4223–4234. doi: 10.1007/s10973-023-12029-z. DOI

Lopes M.S., Catelani T.A., Nascimento A.L.C.S., Garcia J.S., Trevisan M.G. Ketoconazole: Compatibility with pharmaceutical excipients using DSC and TG techniques. J. Therm. Anal. Calorim. 2020;141:1371–1378. doi: 10.1007/s10973-019-09137-0. DOI

Kolisnyk T., Vashchenko O., Ruban O., Fil N., Slipchenko G. Assessing compatibility of excipients selected for a sustained release formulation of biberry leaf extract. Braz. J. Pharm. Sci. 2022;58:e19753. doi: 10.1590/s2175-97902022e19753. DOI

Ramos P. Thermal compatibility assessment of selected excipients used in the oral anti-cancer formulation containing busulfan. Farmacia. 2022;70:417–424. doi: 10.31925/farmacia.2022.3.6. DOI

Rojek B., Wesołowski M. A combined differential scanning calorimetry and thermogravimetry approach for the effective assessment of drug substance-excipient compatibility. J. Therm. Anal. Calorim. 2023;148:845–858. doi: 10.1007/s10973-022-11849-9. DOI

Mateescu M., Vlase G., Budiul M.M., Cernusca B.D., Vlase T. Preliminary study for preparation and characterization of medicated jelly based on ibuprofen or ambroxol. J. Therm. Anal. Calorim. 2023;148:4601–4614. doi: 10.1007/s10973-023-12052-0. DOI

Harmathy Z., Konkoly Thege I. Application of modern thermal methods in pharmaceutical analysis. Acta Pharm. Hung. 1994;64:9–15. PubMed

Giron D. Applications of thermal analysis and coupled techniques in pharmaceutical industry. J. Therm. Anal. Calorim. 2002;68:335–357. doi: 10.1023/A:1016015113795. DOI

Monajjemzadeh F., Ghaderi F. Thermal Analysis Methods in Pharmaceutical Quality Control. J. Mol. Pharm. Org. Process Res. 2015;3:e121.

Gabbott P. Principles and Applications of Thermal Analysis. Blackwell Publishing; Oxford, UK: 2008.

Akash M.S.H., Rehman K. Essentials of Pharmaceutical Analysis. Springer; Singapore: 2020. Differential thermal analysis.

Hanwell G.R., Curtis M.D., Lonie D.E., Vandermeersch D.C., Zurek T., Hutchison E. Avogadro: An Advanced Semantic Chemical Editor, Visualization, and Analysis Platform. J. Cheminform. 2012;4:17. doi: 10.1186/1758-2946-4-17. PubMed DOI PMC

Neese F. The ORCA program system. WIREs Comput. Mol. Sci. 2012;2:73–78. doi: 10.1002/wcms.81. DOI

Lu T., Chen F. Multiwfn: A multifunctional wavefunction analyzer. J. Comput. Chem. 2012;33:580–592. doi: 10.1002/jcc.22885. PubMed DOI

Echavarria A.P., Pagan J., Ibarz A. Kinetics of color development in glucose/Amino Acid model systems at different temperatures. Sci. Agropecu. 2016;7:15–21. doi: 10.17268/sci.agropecu.2016.01.02. DOI

Sovizi M.R., Hajimirsadeghi S.S., Naderizadeh B. Effect of particle size on thermal decomposition of nitrocellulose. J. Hazard. Mater. 2009;168:1134–1139. doi: 10.1016/j.jhazmat.2009.02.146. PubMed DOI

Füglein E., Mende S., Jung S., Schneider T. About the Infl uence of the Particle Size on the Thermal Behavior of Inorganic Powders. Prod. Der Partik. 2008;4:97.

Zauska L., Urbanova M., Brus J., Zelenak V., Hornebecq V. Adsorption and release properties of drug delivery system naproxen-SBA-15: Effect of surface polarity, sodium/acid drug form and pH. J. Funct. Biomater. 2022;13:275. doi: 10.3390/jfb13040275. PubMed DOI PMC

Rowe R.C., Sheskey P.J., Quinn M.E. Handbook of Pharmaceutical Excipients. 6th ed. Pharmaceutical Press; London, UK: 2009.

Ramos P. Compatibility studies of selected mucolytic drugs with excipients used in solid dosage form: Thermogravimetry analysis. Farmacia. 2021;69:585–594. doi: 10.31925/farmacia.2021.3.22. DOI

Pratiwi M., Ylitervo P., Pettersson A., Prakoso T., Soerawidijaja T.H. Magnesium stearate production via direct reaction of palm stearine and magnesium hydroxide. IOP Conf. Ser. Mater. Sci. Eng. 2017;206:012026. doi: 10.1088/1757-899X/206/1/012026. DOI

Pereira M.A.V., Fonseca A.A., Silva-Junior A.A., Fernandes-Pedrosa M.F., de Moura F.V., Barbosa E.G., Gomes A.P.B., dos Santos K.S.C.R. Compatibility study between chitosan and pharmaceutical excipients used in solid dosage forms. J. Therm. Anal. Calorim. 2014;116:1091–1100. doi: 10.1007/s10973-014-3769-4. DOI

Mirakami F.S., Lang K.L., Mendes C., Cruz A.P., Carvalho Filho M.A.S., Silva M.A.S. Physico-chemical solid-state characterization of omeprazole sodium: Thermal, spectroscopic and crystallinity studies. J. Pharm. Biomed. Anal. 2009;49:72–80. doi: 10.1016/j.jpba.2008.10.005. PubMed DOI

Raijada D., Bond A.D., Larsen F.H., Cornett C., Qu H., Rantanen J. Exploring the Solid-Form Landscape of Pharmaceutical Hydrates: Transformation Pathways of the Sodium Naproxen Anhydrate-Hydrate System. Pharm. Res. 2013;30:280–289. doi: 10.1007/s11095-012-0872-8. PubMed DOI

Kuthi F.A.A., Norzali N.R.A., Badri K.H. Thermal characteristics of microcrystalline cellulose from oil palm biomass. Malays. J. Anal. Sci. 2016;20:1112–1122.

Listiohadi Y., Hourigan J.A., Sleigh R.W., Steele R.J. Thermal analysis of amorphous lactose and α-lactose monohydrate. Dairy Sci. Technol. 2009;89:43–67. doi: 10.1051/dst:2008027. DOI

Chena J., Wang J., Li R., Lu A., Li Y. Thermal and X-ray Diffraction Analysis of Lactose Polymorph. Proc. Eng. 2015;102:372–378. doi: 10.1016/j.proeng.2015.01.165. DOI

Altamimi M.J., Wolff K., Nokhodchi A., Martin G.P., Royall P.G. Variability in the α and β anomer content of commercially available lactose. Int. J. Pharm. 2019;555:237–249. doi: 10.1016/j.ijpharm.2018.10.061. PubMed DOI

López-Pablos A.L., Leyva-Porras C.C., Silva-Cázares M.B., Longoria-Rodríguez F.E., Pérez-García S.A., Vértiz-Hernández A.A., Saavedra-Leos M.Z. Preparation and Characterization of High Purity Anhydrous β-Lactose from α-Lactose Monohydrate at Mild Temperature. Int. J. Polym. Sci. 2018;2018:5069063. doi: 10.1155/2018/5069063. DOI

Al-Hada N.M., Saion E.B., Shaari A.H., Kamarudin M.A., Flaifel M.H., Ahmad S.H., Gene S.A. A facile thermal-treatment route to synthesize ZnO nanosheets and effect of calcination temperature. PLoS ONE. 2014;9:e103134. doi: 10.1371/journal.pone.0103134. PubMed DOI PMC

Balek V., Šubrt J., Pérez-Maqueda L.A., Beneš M., Bountseva I.M., Beckman I.N., Pérez-Rodríguez J.L. Thermal behavior of ground talc mineral. J. Min. Metall. B Metall. 2008;44:7–17. doi: 10.2298/JMMB0801007B. DOI

Jamrógiewicz M., Milewska K., Mikolaszek B. Spectroscopic Evaluation on Pseudopolymorphs of Sodium Naproxen. Spectrochim. Acta Part A Mol. Biomol. Spectrosc. 2021;261:120018. doi: 10.1016/j.saa.2021.120018. PubMed DOI

Ilic-Stojanovic S., Nikolic V., Nikolic L., Zdravkovic A., Kapor A., Popsavin M., Petrovic S. The Improved Photostability of Naproxen in the Inclusion Complex with 2-Hydroxypropyl-β-Cyclodextrin. Hem. Ind. 2015;69:361–370. doi: 10.2298/HEMIND131128050I. DOI

Sarkar A., Sengupta K., Chatterjee S., Seal M., Faller P., Dey S.G., Dey A. Metal Binding to Aβ Peptides Inhibits Interaction with Cytochrome c: Insights from Abiological Constructs. ACS Omega. 2018;3:13994–14003. doi: 10.1021/acsomega.8b01736. PubMed DOI PMC

Pratiwi R.A., Nandiyanto A.B.D. How to read and interpret UV-VIS spectrophotometric results in determining the structure of chemical compounds. Indones. J. Educ. Res. Technol. 2022;2:1–20. doi: 10.17509/ijert.v2i1.35171. DOI