Bioadhesive gel containing 5 % acyclovir for the treatment of herpes labialis: Preclinical development

Acyclovir is widely indicated for the treatment of herpes labialis, an infection typically caused by herpes simplex virus 1 (HSV-1). The standard treatment is based on the use of this antiviral in conventional topical semi-solid formulations (ointments, creams or gels), which have limitations such as low skin adherence and poor patient compliance. On the other hand, therapeutic bioadhesive gels (TBG) are semi-solid formulations that form a thin and transparent polymeric film in situ, displaying superior cosmetic attributes than conventional semi-solid forms and offering improved skin maintenance and patient compliance. In this study, a TBG containing 5 % of acyclovir was developed and characterized in terms of assay, impurities, appearance, pH, viscosity, particle size and morphology and microbiology count, complying with specifications. Stability studies showed that acyclovir-TBG was stable for at least 3 years under the experimental conditions carried out according to the International Council for Harmonisation (ICH) guidelines. Moreover, its cosmetic attractiveness and film-forming ability were considered positive and the in vitro penetration studies revealed a 23.8-fold increase in acyclovir retained percentage in the skin compared to the reference product Zovirax (R) (11.9 vs 0.5 % after 24 h, respectively). Finally, in vivo skin and ocular irritation studies as well as dermal tolerance studies did not show any negative sign in the macroscopic and microscopic examination. Thus, the proposed formulation could be a good and safe alternative for the topical treatment of lesions caused by HSV-1.