Study Of A Gelrite/alginate-based In Situ Gelling Ophthalmic Delivery System For Matrine

An ideal ophthalmic formulation should be administrated in eyedrop form, without causing blurred vision or irritation. The formulation will not be eliminated from the precorneal area immediately upon instillation because of lachrymation and effective riasolacrimal drainage. So it could slow down the drug elimination and lengthen the residence time of vehicle on ocular surface.In this study, we describe an alternative in situ gelling system prepared by the combination of Gelrite and alginate. The rheological behaviors of various polymer solutions under different conditions were analyzed. High performance liquid chromatograph was adopted to measure the contents of Gelrite/alginate-based in situ gellings. In addition, the in vitro matrine release and in vivo precorneal retention of different drug-containing formulations were characterized to evaluate the use of in situ gelling polymer solutions for ocular drug delivery. The effect of formulation characteristics on ocular irritation study was investigated. As a complement, the results of stability studies, in vitro permeability studies and the ability to inhibit ocular inflammation were obtained.It was found that the optimum concentration of Gelrite solution for the in situ gel forming delivery systems was 0.3%(w/w), and that for alginate solution was 1.4% (w/w). The mixture of 0.2%Gelrite and 0.6%alginate solutions showed a significant enhancement in gel strength at physiological condition. Preparations were made isotonic by the addition of mannitol (5%, w/v), and the pH was adjusted to 8.0 using hydrochloric acid. The viscosity of Gelrite/alginate solutions all decreased as the shear rate increased, which showed the characteristic of pseudoplastic fluid. The viscosity of preparation increased at first, and above the critical point of tear fluid ratio, it began to decrease. The linear relationships for matrine between 10-60ug/ml were good, R= 0.999. The average recovery rate was 97.4%, RSD was 1.7%. RSD in one day was 1.29%. The drug contents of the preparations were 98.2%,99.4%and 98.5%. The polymer solutions might be considered as minimally irritating to the eye of the rabbits. Excellent ocular tolerance was noted. Both in vitro and in vivo results indicated that the combined polymer systems performed better in retaining matrine than the individual solutions.The initial stability investigation was performed. The results of the influential factor experiments indicated that the preparations should be preserved away from light and under shady place. The accelerated stability experiments demonstrated that they have satisfactory stability and possess validity duration up to two years. The 1% propanediol was effective and safe penetration for matrine and the gel was non-irritant for CAM. The preparation could markedly inhibit ophthalmic inflammation caused by the tincture of chili compared with the control group (P<0.05).The preparation was stable, safe, anti-irritation and effective for the experimental ophthalmia, while using HPLC to control its quality was feasible. For the polymer solutions, formulations 15 and 16 had better performance than the formulation with Gelrite and alginate, formulation 16 (0.2%Gelrite/0.6%alginate) had the best retentive effect among them and could improve ocular bioavailability of matrine. Therefore, the Gelrite/alginate system can be used as the in situ gelling vehicle for ophthalmic drug delivery.