Synergy of Tetracyclines and Potassium Azeloyl Diglycinate (Azeloglycine) in Hydrogels: Evaluation of Stability, Antimicrobial Activity, and Physicochemical Properties

Acne vulgaris is one of the most common dermatological diseases and has a complex etiology. Despite the wide range of available therapeutic options, modern and effective solutions are still being sought, particularly in the area of topical therapy. The aim of this study was to develop hydrogel formulations that provide stability for the antibiotics they contain-tetracycline or chlortetracycline enriched with azeloglycine-the latter an ingredient supporting acne-prone skin care. The physicochemical parameters, stability, and antimicrobial activity of the obtained formulations were analyzed. HPLC analysis showed that tetracycline exhibited greater stability than chlortetracycline, especially in mildly acidic and neutral environments. The addition of azeloglycine improved the rheological properties of the hydrogels, reduced tetracycline degradation under alkaline conditions, and enhanced the penetration of active ingredients into the model sebum. All tested formulations demonstrated antimicrobial activity against <i>Staphylococcus aureus</i>. In the artificial sebum biofilm model, hydrogels containing azeloglycine more effectively reduced staphylococcal biofilm mass. No formulations showed toxicity towards <i>Galleria mellonella</i> larvae. The results indicate the potential usefulness of the developed hydrogels as modern multifunctional formulations for topical acne treatment. Hydrogel formulations containing tetracycline and azeloglycine may represent a promising future anti-acne preparation exhibiting synergistic antibacterial, anti-inflammatory, and sebum-cleansing effects.