Liposomes as potential carriers for ketorolac ophthalmic delivery: formulation and stability issues / Liposomes as potential carriers for ketorolac ophthalmic delivery: formulation and stability issues

ABSTRACT Drug delivery to treat ocular disorders locally is a challenging endeavor. Traditional ocular dosage form - eye drops - exhibits poor availability, consequently inefficient therapeutic response. The objective of the study was to formulate and characterize a ketorolac tromethamine ocular system with a prolonged release pattern based on liposomes as a vesicular carrier and to design once daily liquid preparation realizing the thermal in situ gelation principle. Liposomes were prepared by film hydration method. The influence of cholesterol concentration, pH and volume of hydration medium, and type and concentration of charging imparting agents were studied. Liposomes were characterized via, morphological examination, vesicular size, and encapsulation efficiency, and in vitro release performance, moreover its stability was assessed. The results obtained highlighted that liposomes showed a closed vesicular multi-lamellar structure. Ketorolac was successfully encapsulated within the liposomal structure in a cholesterol and charge inducing agent concentration-dependent behaviour. The dispersion of liposomes within thermosensitive Poloxamer in situ gel was able to retard the release of the drug by diffusion providing a controlled prolonged delivery. The liposomal formulations were physically stable for six months. Ketorolac tromethamine in situ liposomal gel representing an efficient alternative in terms of ocular retention and patient compliance when compared with conventional eye drops.

Effect of preservative, antioxidant and viscolizing agents on in vitro transcorneal permeation of ketorolac tromethamine.

The influence of formulation additives, e.g. preservative, antioxidant and viscolizing agents on in vitro transcorneal permeation of ketorolac tromethamine from 0.5%(w/v) aqueous drop was studied using goat cornea. Permeation characteristics of drug, from selected formulations, through excised rabbit cornea were also evaluated. Aqueous solution of ketorolac tromethamine (0.5% w/v), pH 6.5 or 7.0 having ionic strength 0.2, was prepared. To this solution perservatives either alone or in combination with other additives were added to have drops of various composition. Permeation studies with goat cornea showed maximum permeation of ketorolac tromethamine from formulation containing benzalkonium chloride and disodium edetate. Increase in viscosity of drop resulted in decreased permeation of drug. Formulation containing benzalkonium chloride and disodium edetate also increased permeation of drug through rabbit cornea. Cumulative permeation of drug through rabbit cornea was found to be 2.3-2.4 fold higher than that observed with goat cornea.