FORMULATION AND EVALUATION OF pH TRIGGERED IN SITU GELLING OPHTHALMIC SUSTAINED DRUG DELIVERY SYSTEM OF CIPROFLOXACIN HYDROCHLORIDE

The lower residence contact time of drug, higher tear turnover, limited surface area of contact and impermeability of corneal epithelium layer are the reasons of poor bioavailability of conventional ophthalmic dosage forms. The purpose of this study is to formulate ciprofloxacin hydrochloride (HCl) in situ gelling ophthalmic drug delivery system based on pH of tear fluid for better bioavailability and minimising frequent instillation. This system includes pH sensitive polymer (Carbopol 934p) as a gelling agent and HPMCK15M as a viscosity enhancer which are instilled as a drop and undergo sol-gel transition in the cul-de-sac. Central composite design with two independent factors (Carbopol 934p and HPMCK15M) followed by contour plot and surface response was used to optimise formulation (Optimized). The drug was complexed with Indion® 254 to avoid drug-Carbopol 934p instantaneous incompatibility. The rheological study of Optimized exhibited pseudoplastic behaviour with adequate viscosity at higher pH (7.40 or above). It provided prolonged drug release time (8 hours). It followed Krosmeyer–Peppas model with non-Fickian diffusion. Theocular irritancy based on hen’s egg test-chorioallantoic membrane (HET-CAM) technique suggested that it had acceptable mild irritancy (0.33, 0.66 and 0.66 out of 3 at 6th, 7th and 8th hours, respectively). It retained its antimicrobial response towards Pseudomonas aeruginosa (ATCC 10145) and Staphylococcus aureus (ATCC 25903). The results of gelling capacity, rheological behaviour and in vitro release studies of F_optimized demonstrated that Carbopol 934p–HPMCK15M composite can help to enhance ocular bioavailability.