STUDY OF THE IMPACT OF STRESS CONDITIONS ON THE STABILITY OF NAFITIFINE HYDROCHLORIDE IN A CREAM DOSAGE FORM AS PART OF THE DEVELOPMENT OF AN ANALYTICAL METHOD FOR IMPURITY CONTROL

Abstract

Introduction. The stability of active pharmaceutical ingredients in dosage forms is a key determinant of their quality and safety throughout the shelf life. Stress testing enables identification of the most vulnerable degradation pathways and provides insight into impurity profiles formed under extreme storage conditions. The Aim of the Study. To evaluate the behavior of naftifine hydrochloride in cream formulations under the influence of various stress factors and to determine the characteristics of degradation products formed under different types of stress conditions. Research Methods. The study was performed using an Agilent 1200 liquid chromatograph equipped with a diode-array detector (DAD). Chromatographic data acquisition and integration were carried out using OpenLab software. The chromatographic columns Synergi Hydro-RP (250 × 4,6 mm, 4 μm) and Gemini C18 (50 × 4,6 mm, 3 μm) were purchased from Phenomenex. Reference standards of naftifine hydrochloride (purity ≥ 99 %, HPLC grade) were obtained from USP; cinnamaldehyde (CA) and N-methyl-1-naphthalenemethylamine hydrochloride (purity ≥ 99 %, HPLC grade) were purchased from Sigma-Aldrich Chemicals Co. Commercial medicinal products included Esthesiphene® cream (Farmak JSC, Ukraine) and Exoderil® cream (Sandoz GmbH, Austria). Results and Discussion. Under most tested conditions – including acidic, alkaline, thermal, and light exposure – the chromatographic profiles remained largely unchanged, indicating good chemical stability of naftifine in the studied cream matrices. Marked changes were observed only under oxidizing conditions: new peaks appeared on the chromatograms, the intensity of several impurities increased substantially, and a distinct oxidative degradation pattern was formed, accompanied by a measurable decrease in the content of the active substance. High peak purity values and an acceptable mass balance confirmed the reliability of the detected changes and ensured confident discrimination between degradation products and matrix-related components. Conclusions. The study demonstrated that naftifine hydrochloride in cream formulations remains stable when exposed to acidic, alkaline, thermal, and photolytic conditions, whereas oxidizing conditions lead to significant degradation and the formation of specific oxidation products. These results highlight the susceptibility of the API to oxidation and provide important information for defining appropriate storage recommendations and supporting long-term stability assessment. The applied chromatographic method allowed the clear detection of impurity profile changes and is suitable for continued monitoring of degradation processes in further stability studies.