Chitosan/HPMC-based mucoadhesive film co-loaded with fluconazole and ofloxacin for management of polymicrobial keratitis

Bacterial and fungal co-infection leads to polymicrobial keratitis (PMK). The current study produced swellable mucoadhesive biopolymeric films composed of chitosan, HPMC, and glycerol using cast drying method. The film was dual-loaded with fluconazole (FCZ) and ofloxacin (OFX) to treat PMK. The prepared film exhibited excellent thickness, folding endurance, surface pH, tensile strength, and stability characteristics. In addition, it also exhibited good in vitro antimicrobial activity, ex-vivo mucoadhesion, and corneal permeation. AUC (0-∞) and MRT were 6.5 and 5.2-fold higher for a film containing FCZ and 22.5 and 2.5-fold higher for a film containing OFX than their marketed formulations. PK-PD simulation study supports desired efficacy of the proposed dosage form. Thus, the film exhibits longer pre-corneal drug residence time and enhanced ocular bioavailability, most likely resulting in high patient compliance. The proposed film could be a prominent replacement for the existing dosage form and may present a viable alternative for the treatment of PMK.