Study On Timolol Maleate Gel For Ophthalmic Use

In order to increase the residence time and improve the bioavailability of a drug, a kind of ophthalmic gel has been studied. Hydroxypropyl Methylcellulose(HPMC K4M) has been used as the base of gel. Timolol Maleate is a kind of drug that is used frequently to cure glaucoma has been chosen as model drug to develop a kind of gel for ophthalmic usage.The first job is to screen the polymer that can be used as gel base. We have made gel bases from HPMC K4M and Carbomer-940 of different concentration, respectively. We have studied the viscosity and fluidity of these gel bases and have confirmed the concentration range of HPMC K4M and Carbomer-940, respectively.In the investigation of formulation optimization of the ophthalmic gel, study on the change of viscosity and drug-release rate of gel from different polymer have been carried out. The viscosity of gels has been determinated by NDJ-1 rotational viscometer. The drug release experiment in vitro has been carried out in the apparatus that is designed by us, in which; the simulated tear fluid has been used as medium. We have evaluated the viscosity and drug-release rate of different formulations at the same time. The optimized TM gel possesses good viscosity and appropriate drug-release rate. It can increase the ocular residence time of drug, bioavailability can be improved too. The gel has good performance for ophthalmic usage. And we have decided the amount of wetting agent , bacteriostatic agent , metal chelator, antioxidant, respectively.We have used UV and RP-HPLC to determinate content of Timolol Maleate gel for ophthalmic usage, respectively. By the UV method, the linear range of Timolol Maleate is 5.0⁴0.0mg·L^-1 ,r=0.999 1. The labeled amount of three batch samples are 100.7% (RSD=1.21%), 98.8% (RSD=1.03%), 98.5% (RSD=0.94%) , respectively. By the RP-HPLC method, the analytical column is Diamonsil C 18(5 μm, 4.6mm×250mm), the mobile phase is methanol-water-triethylamine (50 : 50 : 0.1, adjust pH to 5.0 with phosphoric acid); The flow rate is 1.0mL·min^-1; the detectionwavelength is 294nm; the column temperature is 30°C.Timolol Maleate can be completely separated from the degraded products. The number of theoretical plate calculated for Timolol is over 3000. The linear range of Timolol Maleate is 20-lOOmgL'1 ,r=0.999 5. The labeled amount of three batch samples are 100.4% (RSD=0.65 %), 99.1 % ( RSD=0.91%), 100.7% (RSD=0.54 %) , respectively. The stability of samples has been tested by room temperature storage. Result indicate thatpH> viscosity n content and appearance of gel have not changed obviously.At last, the pharmacodynamics and stimulation of gel have been evaluated. Curative effect of ophthalmic gel and eye drops has been compared by two kinds of animal models. The in vivo test shows that the efficacy of ophthalmic gel is better than that of eye drops. The test of stimulation has suggested the gel has no stimulation on rabbit conjunctiva.