Development of Film Formulations of Acyclovir as Safe and Effective Antiviral Agent: Optimization, In Vitro Characterization and Antialphaherpesviral Efficacy

Introduction: A novel acyclovir (ACY) buccal film was developed using a biodegradable chitosan/polyacrylic acid (CS/PAA) blend as a safe and effective approach for the treatment of herpes simplex virus (HSV) infections. Methods: CS/PAA buccal film formulation was systematically optimized using a 3² factorial design to evaluate the effects of polymer ratios and processing variables on critical quality attributes, including mucoadhesive strength, elastic modulus, swelling index, and cumulative release. The optimized film, obtained at a drying temperature of 40 °C, comprised 1.2% CS, 0.4% PAA, and 5% w/w ACY. Results: Physicochemical characterization confirmed the compatibility of the drug and excipients without undesirable interactions, while swelling and mucoadhesion studies demonstrated adequate hydration and strong adhesive properties suitable for buccal application. Mechanical analysis revealed a favorable balance between flexibility and tensile strength, ensuring patient comfort and handling feasibility. In vitro release studies indicated sustained drug release, with the optimized formulation achieving approximately 85% cumulative release over 12 h while minimizing burst effect. Moreover, antiviral efficacy studies confirmed significant inhibition of alphaherpesviral activity. Discussion: These findings demonstrate that the optimized CS/PAA buccal film provides controlled drug release, strong mucoadhesion, and suitable mechanical properties, supporting improved local drug retention and therapeutic performance. Conclusion: Collectively, these results suggest that the ACY-loaded CS/PAA film represents a systematically optimized and multifunctional controlled-release platform with potent antiviral activity, offering a promising alternative to conventional oral formulations for the management of HSV infections.