酮咯酸氨丁三醇眼用凝胶剂的制备工艺与质量控制

Preparation and quality control of ketorolac tromethamine eye gel

目的制备酮咯酸氨丁三醇眼用凝胶并建立其质量控制方法。方法以卡波姆-934为凝胶基质,制备了酮咯酸氨丁三醇眼用凝胶;采用高效液相色谱法测定酮咯酸氨丁三醇和有关物质的含量,色谱条件为Dikma C18柱(150 mm×4.6 mm,5μm),以甲醇-1%冰醋酸(68:32)为流动相,柱温为室温,检测波长为323 nm,流速为1.0mL min-1;考察了酮咯酸氨丁三醇眼用凝胶的刺激性和过敏性。结果处方为卡波姆-9340.05%,玻璃酸钠0.05%,丙二醇5.0%,硼砂1.0%,苯扎氯铵0.01%,pH为6.5～8.0。酮咯酸氨丁三醇检测浓度与峰面积在0.200～0.640 mg mL-1线性关系良好(r=0.999 8),平均回收率为100.1%(RSD=0.2%,n=9)。经加速试验和室温留样考察,其外观性状、pH值、有关物质及含量等指标均无明显变化。酮咯酸氨丁三醇眼用凝胶的局部刺激性和过敏性呈阴性。结论该凝胶剂制备工艺简单、可行,稳定性好,质量可控。

Objective To prepare and establish the quality control for ketorolac tromethamine eye gel.Methods Ketorolac tromethamine eye gel was prepared with Carbomer-934.The content of ketorolac tromethamine was determined by HPLC at the wavelength of 323 nm with a Dikma C18（150 mm×4.6 mm,5 μm） column with the mobile phase consisting of a mixture of methanol-1% glacial acetic acid（68 ： 32,v/v）.The flow rate was 1.0 mL min-1at room temperature.The stimulation and hypersensitivity of ketorolac tromethamine eye gel for the skin were investigated.Results The eye gel was prepared by 0.5% carbomer-934,0.05% sodium hyaluronate,5.0% 1,3-propanediol,1.0% borax and 0.01% benzalkonium chloride.The pH value was 6.5-8.0.There was a good linear correlation at 0.200-0.640 mg mL-1（r = 0.999 8） of ketorolac tromethamine concentration;the average recovery was 100.1%（RSD = 0.2%,n = 9）.The appearance,pH value,related substances and content of ketorolac tromethamine ophthalmic eye gel had no difference by acceleration experiment and room temperature storage experiment.Local stimulation and hypersensitivity test were all negative.Conclusion The eye gel is prepared simply with good stability.The analytical method is convenient with satisfactory recovery and good reproducibility.It can be used for the quality control of ketorolac tromethamine eye gel.