| OBJECTIVE To study the method for the preparation of CsA in ophthalmic situ-forming gel,including the preparation technique,quality control and stability,to investigate its release pattern in vitro,and to provide support experimental evidence for new preparationsMETHODS①Orthogonal design was used to screen the formulas according to the viscosity and drop.The final formula was established based on its accumulated release amount in vitro.②The dynamic viscosity of in situ-forming gel was determined by rotating-speed meter to obtain its rheological characteristics.③A reversed-phased high performance liquid chromatographic method was developed to analyze the content of cyclosporine.Chromatographic condition was as follows: Thermo(r)C18column and acetonitrile and water(90:10)were used for the separation and the detective wavelength was 210 nm,and the flow rate was 0.7 mL·min-1.④The content of CsA released from the gel base at different time was determined by HPLC,and its rule of release in vitro was explored.⑤We studied the retention of the two preparations in the cornea with time-concentration course by comparing CsA ophthalmic situ-forming gel with CsA eye drops.⑥The characteristics,pH values, viscosity and content changes were observed and analyzed under high temperature,high humidity,room temperature,and acceleration test respectively.⑦The irritation of CsA in ophthalmic situ-forming gel was evaluated though single dosing and multiple dosing irritation tests.RESULTS①The best formula was composed of 0.5%CsA,1% vitamin AD,0.15%CP and 0.5%HPMC.②The better bogus plastic liquid characteristics were found as the shear rate increased and the viscosity of gel descended.③The linearity of CsA fit well within 5～60μg·mL-1and the correlation coefficient was 0.9996.The average recoveries of CsA in low,middle and high concentrations were 99.30%, 99.80%,and 98.90%,respectively(n=3).RSD of the inter-day and intra-day was 1.02%and 1.82%(n=5).The contents of the three gels were 98.5%,100.4%,and 98.86%,respectively.④CsA in ophthalmic situ-forming gel showed slow-release characteristics and its release drug mathematic models followed the first-order reaction.⑤The retention of the drug in the cornea of CsA ophthalmic situ-forming gel was obviously longer than that of CsA eye drops.⑥The preparation was stable under light and humidity,but it was unstable at high temperature,so it should be stored in cool places.⑦Irritation tests showed CsA ophthalmic situ-forming gel was safe.CONCLUSION①This preparation method is simple,reasonable and the preparation is stable.②The HPLC method is sensitive and effective for the quality control of CsA in ophthalmic situ-forming gel.③The preparation proved to be able to extend the retention in the cornea and so increased the drug absorption.④CsA in ophthalmic situ-forming gel is safe after single dosing and multiple dosing irritation tests.
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