左炔诺孕酮片溶出度方法研究及制剂学评价

目的: 建立水中不溶性药物左炔诺孕酮片溶出度测定方法,为药品的质量控制和制剂学评价提供依据。 方法: 采用中国药典2010年版二部附录溶出度测定法第二法,以0.1% 十二烷基硫酸钠(SDS)的0.1 mol·L^-1盐酸溶液1000 mL为溶出介质,转速为75 r·min^-1,取样时间为45 min。采用高效液相色谱法,色谱柱为MGⅡC₁₈柱(4.6 mm×150 mm,5 μm),流动相:乙腈-水(70∶30),流速1.0 mL·min^-1,检测波长240 nm。 结果: 左炔诺孕酮在0.12~3.03 μg·mL^-1浓度范围内线性关系良好(r =0.9999);平均回收率为98.3%,RSD为0.5%(n=9),溶液在18 h内稳定,滤膜对左炔诺孕酮没有吸附。按照拟定标准的限度(75%),2011年国家评价性抽验的83批次样品中符合拟定限度要求的为71.1%,其中2家企业的所有产品均低于拟定限度要求。经调研,溶出度结果与处方工艺密切相关。通过对原研制剂和国内制剂在溶出介质和水中的溶出曲线测定和f₂因子的计算,得出本溶出度方法具有很强的区分能力。 结论: 本研究建立的溶出度方法操作简单,准确,稳定性好,区分能力强,满足左炔诺孕酮片质量控制和制剂学评价的要求。

Objective: To establish a method for testing the dissolution of levonorgestrel tablets to provide the basis for drug quality control and pharmaceutical evaluation. Methods: The dissolution test method in the Apparatus Ⅱof ChP(2010 edition)Vol Ⅱwas used,the dissolution medium was 0.1 mol·L^-1 hydrochloric acid solution(1000 mL)containing 0.1% SDS.The rotation speed was 75 r·min^-1.The sampling time was 45 minutes.Then the dissolution was analyzed by HPLC method.A MGⅡC₁₈ (4.6 mm×150 mm,5 μm)column was used and a mixture of acetonitrile and water(70∶30)was used as the mobile phase.The flow rate was 1.0 mL·min^-1,and the detection wavelength was 240 nm. Results: The calibration curve of levonorgestrel was linear in the range of 0.12-3.03 μg·mL^-1(r=0.9999).The average recovery was 98.3%(n=9)with the RSD of 0.5%.The test solution was stable within 18 h and the filter did not interfere with determination as levonorgestrel was not adsorbed on it.The 83 batches of the testing samples for national evaluation in the year of 2011 were tested.Compared to the suggested specification limit(75%),the dissolution of 71.1% of the samples was complied with the limit,among which,however,those of the samples from two manufacturers were all below the suggested limit.After investigation,it was proved that the dissolution results were closely related to the formulation and process of the products.The cumulative dissolution curves of imported reference samples and of native products from seven manufacturers were measured and the f₂ factors were obtained which showed that the dissolution method was of strong differentiation ability. Conclusion: The method is simple,accurate,stable and with highly distinguishing ability for quality control and pharmaceutical evaluation of levonorgestrel tablets.

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