Formulation and Evaluation of Polyethylene Glycol-based LozengesContaining Fluconazole for the Treatment of Oral Candidiasis

Introduction: This study developed a novel polyethylene glycol (PEG)-based lozenge formulation for buccal delivery of fluconazole, targeting the localized treatment of oral candidiasis. Methods: Lozenges were prepared using PEG 4000 and PEG 400 as a base, combined with carboxymethyl cellulose (CMC), acacia, mannitol, sucralose, and flavoring agents via low-temperature fusion molding. The optimized formulation (F20) was evaluated for organoleptic properties, weight variation, friability, drug content, in vitro dissolution/disintegration, hardness, stability, FTIR, DSC, and drug release kinetics. Results: The best formulation demonstrated a uniform, opaque lozenge (mean weight 2.02 ± 0.07 g) with a pleasant taste, low friability (0.15%), and high hardness (11.85 ± 1.91 kg/cm²). DSC analysis confirmed the conversion of crystalline fluconazole into an amorphous state within the lozenge matrix. Drug release (~50% at 30 min, ~80% at 50 min) followed Higuchi’s kinetic model (R² = 0.9453). Stability studies confirmed physicochemical integrity and acceptable drug content (90–110%) for 3 months at 4°C and 28°C; however, PEG 400 leakage occurred at 40°C. Discussion: This study successfully established a novel, stable, and palatable PEG/CMC-based lozenge formulation for fluconazole, featuring amorphous drug dispersion for enhanced solubility and controlled disintegration for prolonged buccal retention. Sucralose provided superior palatability compared to saccharin. The formulation exhibited unique swelling and jelly-like disintegration behavior with a diffusion-controlled release mechanism. FTIR analysis confirmed excipient compatibility and the absence of chemical degradation. Conclusion: This formulation offers a promising, patient-friendly alternative for localized therapy, potentially reducing systemic side effects such as first-pass metabolism and gastric irritation. Clinical efficacy studies are warranted.