氯雷他定片溶出度测验方法的改进

Improved Dissolution Method of Loratadine Tablets

关键词:  氯雷他定片  溶出度  生物药剂学分类系统  高效液相色谱法

Key words:  loratadine tablets  dissolution  biopharmaceutics classification system  HPLC

摘要:

目的 改进氯雷他定片的溶出度测验方法，考察国内31家企业氯雷他定片的内在质量。方法 根据本品的溶解吸收特性，采用生物药剂学分类系统Ⅱ类药物的两点测定法，拟定既符合氯雷他定人体吸收特点又能区分产品内在质量的溶出度检查方法。采用浆法，以pH 3.0缓冲液为溶出介质，转速为75 r·min^-1。液相色谱条件：Agilent TC-C₁₈(4.6 mm×250 mm，5 μm) 色谱柱，流动相为乙腈-水(含0.5%二乙胺，用磷酸调pH值为3.0±0.05)(60∶40)；检测波长为247 nm，流速：1.0 mL·min^-1，柱温：35 ℃；进样量：20 μL。结果 氯雷他定在1.006~32.176 μg·mL^-1内呈现良好的线性关系，r=1.000，采用此法检测31家企业各若干批样品的溶出度，不合格率达74.7%，与溶出曲线考察结果一致。结论 拟定的溶出试验方法更能体现药品的生物利用度，溶出液测定方法准确、重现性好、操作简单。对全国范围样品考察结果显示，方法能够有效控制产品的内在质量。

Abstract:

OBJECTIVE To improve a test method for the dissolution of loratadine tablets to inspect the determination of loratadine tablets from 31 factories in China. METHODS According to loratadine tablets’ speciality of dissolution and absorption, set a discriminating specification for dissolution testing, using two points for biopharmaceutics classification system Ⅱ drugs’ assessment. The dissolution was determined by paddle method, the medium was pH 3.0 buffer solution, and rotate speed was 75 r·min^-1. The chromatographic condition was Agilent TC-C₁₈(4.6 mm×250 mm, 5 μm) column, the mobile phase consisted of acetonitrile and water(0.5% diethylamine adjusted to pH 3.0 with phosphoric acid) (60∶40), the wavelength of UV detector was 247 nm; the flow rate was 1.0 mL·min^-1, the injection volume was 20 μL. RESULTS The calibration curve was liner in the concentration range of 1.006-32.176 μg·mL^-1, r=1.000; several samples from 31 factories were detected using this method and the fraction defective was 74.7%. CONCLUSION The improved method shows more biological availability than before, and the assay method is accurate, highly specific and widely applicable. Through the investigation of samples from the whole country, it is shown that the method developed can be applicable to all the samples and effectively control the internal-quality of product.