Abstract Stimuli sensitive hydrogels are hydrophilic , three dimensional networks, which are able to imbibe large amount of water or biological fluids and undergoes a phase transition after receiving a specific stimulus. Ophthalmic drug delivery is often impaired by removal mechanism (blinking, tears) and by the barriers of the pre corneal areas and further patients do not seek medical attention until the disorder is well established because of lack of symptoms. Conventional topical treatments have measure drawbacks including poor ocular bioavailability i.e. less than 5 % of administered active drug is absorbed or becomes available at the site of physiological activity. The reduced therapeutic responses and the poor bioavailability exhibited by the conventional dosage forms are due to rapid pre corneal elimination of the drug, tear turnover, lacrimal drainage and degradation by enzymes. Low absorption results in short duration of action and high frequency of eye drop instillation is associated with discomfort of patients. This problem was solved by using stimuli sensitive hydrogels that are instilled as drops in eye and undergo a phase transition in cul-de-sac. These hydrogels are able to prolong the residence time of drug in pre corneal cavity due to enhanced viscosity by stimulation of pH. The developed hydrogels was therapeutically effacious, stable, non- irritant and In-vitro drug release for 8 hours was observed. Keywords:Timolol maleate, Stimuli Sensitive Hydrogels , viscosity , carbopols. Indian J.Pharm. Educ. Res. 44(4), Oct - Dec, 2010 INTRODUCTION Stimuli sensitive hydrogels are hydrophilic , three dimensional networks, which are able to imbibe large amount of water or biological fluids and undergoes a 1 phase transition after receiving a specific stimulus . This hydrogels approach can be used for the treatment of Glaucoma in ophthalmic drug delivery. Glaucoma comprises a group of chronic conditions that is characterized by progressive deformation of the optic nerve head and elevated intraocular pressure (IOP), a risk factor. It affects primarily the middle aged and elderly, the glaucoma currently constitute second most common 2,3 cause of treatable blindness worldwide . In the ophthalmic drug delivery systems, the physiologicals constraints imposed by the protective mechanism of the eye leads to the low absorption of drugs and results in a short duration of therapeutic action. Excessive frequency of the eye drops instillation is associated with patient non compliance. After instillation of eye drop, the effective tear drainage and blinking action of eye results in a 10 times reduction in the drug 4 concentration with in 4- 20 min . Due to the tear drainage, most of the administered dose passes via nasolacrimal duct into the Gastro Intestinal tract leading to the side effects . Rapid elimination of the eye drops often results in a short duration of the therapeutic effect .The normal volume of tear in the eye is 7 μl whereas a non blinking eye can accommodate a maximum of 30 5 μl of the fluid, the usual single drop size of an instilled eye drop is upto 50 μl and thus most of the drug instilled as eye drop is drained away or lost. Ophthalmic therapy can be improved by increasing the corneal residence time of drugs. Several drug delivery 6 systems are widely used such as ocular inserts, collagen 7 shields etc. These systems are able to prolong the contact time of vehicle on the ocular surface and also slow down drug elimination. However these systems are having some disadvantage such as poor compliance, Indian Journal of Pharmaceutical Education and Research Received on 05/08/2009; Modified on 22/01/2010 Accepted on 03/07/2010 © APTI All rights reserved In vitro and In Vivo evaluation of Stimuli Sensitive Hydrogel for ophthalmic drug delivery a* b c d e Vinod Singh , S.S. Busheetti S Appala Raju , Rizwan Ahmad , Mamta Singh , b Luqman College of Pharmacy, Gulbarga. Karnataka(India). a,d,e SBS PG Institute of Biomedical Sciences & Research , Dehradun, Uttrankhand.(India ). c HKE's College of Pharmacy, Gulbarga, Karnataka (India). *Author for Correspondence: vinod.panipat@gmail.com 380