Formulation And Evaluation Of Ophthalmic Liquid Crystal In-Situ Gel Of Natamycin

Abstract

The eye is considered as a crucial part of our body. We know that because of eye one can be able to see whole world, the nature. If someone lacking this thing or some problem associated with it they only know importance of it. In this research study natamycin an antifungal agent used for the treatment of ophthalmic fungal infections such as fungal keratitis and conjunctivitis was selected as the drug to be delivered to the eye using a sustained release ophthalmic in-situ liquid crystal gelling system. The in-situ gelling system used comprised of GRAS approved excipients with glyceryl mono-oleate (GMO) an emulsifier and stabilizer as the primary excipient. The liquid crystal structural and release mechanism of the gelling system was also studied to establish the utility and potential of the GMO based in situ gel as a drug carrier. Preformulation studies were followed by preliminary formulation and selection of suitable composite. Various compositions of sol containing natamycin in GMO, tween 40, DMSO sol system were prepared and evaluated. From the result discussion the following conclusions are made:PLM used to confirm the liquid crystal structure suggested a lyotropic liquid crystals with lamellar structures for both GMO-tween 40-sol as well as preformed in-situgel system.The pH range for formulation (F1-F5) in both sol and gel form was between pH 6.8 to 7.3, i.e around neutral to slightly alkaline.Fast gelling time was seen for all the GMO-tween 40 formulations (f1-f5) i.e. time for first detection of gelation at 37ºC ± 0.5 ºC was between 90 and 60 sec.The F1 to F5 formulations show high swelling index with the highest index of 102.22 observed for F3 formulation. F3 formulation contains a 1:1 ratio Tween 40 and DMSO respectively.

The viscosity of F2 gel was highest 112.32 cps as it contains no DMSO and comparatively higher surfactant tween 40. F3 formulation also showed sol to gel conversion with high viscosity of 93 cps. In the presence of STF the sol converts to gel resultingincrease in viscosity of gel by approximately tenfold.The release of the drug from the formulation F1, F2 were found to be 95.66 % and 97.63% at the end of 5 and 6 hrs respectively. The formulation F3 showed complete release in 7 hr. The release of drug from formulation F4 and F5 was found to be 98.9% and 96.32 % at the end of 9 and 7 hrs.The antimicrobial studies indicate that natamycin retained its antimicrobial activity after formu­lated into an in-situgel. The drug was active against the selected Candida albicans and Aspergillus fumigatus organism as indicated by zone of inhibition. F3 formulation showed better antimicrobial effects with ZOI of 16 and 15 mm for Candida albicans and Aspergillus fumigates respectively.The best selected formulation (F3) passed the test for isotonocity as the blood cells observed under the optical microscope did not show any observable change (shrinkage due to hyper-tonicity or bulging/ eventual bursting of blood cells due to hypo-tonicity) The in-situ gelling formulations (F3) was non-irritant to rabbit eyes and did not cause any damage to corneal membrane. Finally it may be concluded that F3 in-situ gelling systems comprising of 15%w/w of natamycin in GMO 55%w/w, Tween 40 15%w/w and DMSO 15%w/w showed liquid crystal (lyotropic-lamellar) microstructures with a sustained release of natamycin for 7 hours, the system had good antimicrobial effect against Candida albicans and Aspergillus fumigatus is a thus a potential ophthalmic drug delivery system.