Formulation and Evaluation of Metronidazole Liposomal Gel for Topical and Mucosal Delivery

Background

Metronidazole is a commonly prescribed nitroimidazole antibiotic for Bacterial Vaginosis (BV), rosacea, periodontal infections, and other anaerobic or protozoal infections. However, conventional topical dosage forms suffer from low skin penetration, short duration of action, and reduced therapeutic efficiency, negatively impacting treatment efficacy and patient adherence. Liposomal encapsulation incorporated into a gel base offers a promising strategy to overcome these limitations.

Materials and Methods

Metronidazole-loaded liposomes were prepared by the thin-film hydration method using phosphatidylcholine and cholesterol in a 2:1 (w/w) ratio and subsequently incorporated into a Carbopol® 940 gel base. The optimized liposomal gel was characterized for vesicle size, Polydispersity Index (PDI), zeta potential, Entrapment Efficiency (EE), pH, viscosity, spreadability, and drug content. In vitro drug release was evaluated using the Franz diffusion cell method, and stability was assessed under refrigerated, room temperature, and accelerated storage conditions for 90 days.

Results

The optimized liposomes exhibited a mean vesicle size of 285.4±12.3 nm, PDI of 0.32±0.05, zeta potential of-32.6±2.8 mV, and EE of 68.4±3.2%. The liposomal gel demonstrated satisfactory physicochemical properties: pH 6.2±0.2, viscosity 4,850±245 cps, spreadability 11.4±0.6 g·cm/sec, and drug content uniformity of 98.6±1.4%. In vitro release showed 93.6% cumulative drug release over 24 hr, following anomalous (non-Fickian) transport behavior per the Korsmeyer-Peppas model (n=0.512). The formulation remained stable under refrigerated and room temperature conditions, with notable degradation observed only under accelerated storage.

Conclusion

The metronidazole liposomal gel demonstrated favorable physicochemical characteristics, sustained drug release, and adequate stability, supporting its potential as a once-daily topical and mucosal drug delivery system for conditions such as BV, rosacea, and periodontal infections.