Impact of polymerization reaction conditions on the stability of naproxen sodium.

Abstract

Background: "Smart'" polymers with reversible responsiveness to temperature stimuli are among the most promising carriers for controlled drug delivery, as temperature is a critical physiological factor within the human body. The majority of studies on the coupling of polymers with active substances have employed the method of attaching the drug to the polymer after its synthesis. The direct addition of the drug during the polymerization process has not been attempted, primarily due to concerns about the potential degradation of the active substance under harsh reaction conditions, such as elevated temperature and the presence of free radicals.

Objectives: This study aimed to evaluate the stability of a selected model drug - naproxen sodium (NAP), under extreme synthesis conditions, thereby providing insights into its resilience in such an environment.

Material and methods: The Thermo Scientific Dionex UltiMate 3000 system was utilized for the chromatographic analyses. The separations were carried out on a Phenomenex Kinetex 2.6 µm, C18 100A, 150 × 2.1 mm column at 30°C. A high-performance liquid chromatography (HPLC) assay was carried out using gradient elution with a flow rate 0.4 mL/min and mobile phase of water 0.1% formic acid (A) and acetonitrile 0.1% formic acid (B) with the detector set at the wavelength of 254 nm.

Results: Chromatographic analysis showed new peaks indicating decomposition on NAP in ambient temperature in the presence of 2.2'-azobis(2-methylpropionamidine) dihydrochloride (AIBA).

Conclusion: Our findings indicate that NAP cannot be combined with the polymer during the polymerization process in extreme conditions of synthesis, specifically at temperatures of 70°C and in the presence of radicals, without undergoing decomposition. Nevertheless, further trials and tests are necessary to substantiate this hypothesis. One potential avenue for further investigation would be trials with alternative radical initiators, such as potassium persulfate (KPS).