氯沙坦钾氢氯噻嗪片体外药物释放关键影响因素的研究

Investigation on the Key Factors of Affecting in Vitro Release of Losartan Potassium and Hydrochlorothiazide Tablets

关键词:  氯沙坦钾氢氯噻嗪片  区分性检测  体外释放  包衣组分

Key words:  losartan potassium and hydrochlorothiazide tablets  discriminatory test  in-vitro release  coating components

摘要:

目的 研究影响氯沙坦钾氢氯噻嗪片体外药物释放的关键因素。方法 以pH值3.5缓冲液为溶出介质，采用桨法+沉降篮(转速50 r·min^–1)测定体外溶出量。HPLC色谱柱为Kromasil 100-10 C₈，流动相为0.01 mol·L^–1磷酸二氢钾溶液(pH值2.5)-乙腈(2∶3)，检测波长230 nm，进样量20 μL，流速为2.3 mL·min^–1。结果 研究发现，证实自研片和原研片在该介质中释放差异的主要原因系包衣粉中着色剂不同。进一步研究发现，喹啉黄铝色淀本身的形态和性质在酸介质中有延缓药物释放的作用，此外包衣粉中的水溶性聚合物羟丙纤维素与pH值3.5缓冲液的相互作用也是延缓药物释放的重要因素。结论 速释薄膜包衣粉中着色剂和水溶性聚合物实际上对药物的体外释放有直接的影响。

Abstract:

OBJECTIVE To investigate the key factors of affecting in-vitro release of losartan potassium and hydrochlorothiazide tablets.METHODS The in vitro dissolution of the products were determined by paddle+sinker (the stirring speed was 50 r·min^-1) in pH 3.5 buffer solution as dissolution medium.The HPLC method was adopted using Kromasil 100-10 C₈,with mobile phase of 0.01 mol·L^-1monobasic potassium phosphate solution (pH 2.5)-acetonitrile (2:3),detection wavelength of 230 nm,injection volume of 20 μL,and flow rate of 2.3 mL·min^-1.RESULTS It was found that the coloring agent in the coating powder for the tablets was the main reason for the difference in dissolution between the self-prepared formulation and reference listing drug.Through further investigation,it was found that the morphology and properties of aluminum lakes could delay drug release in acid medium.In addition,the interaction between aqueous polymer hydroxypropyl-cellulose and pH 3.5 buffer solution was also an important factor toward delaying the drug release.CONCLUSION The types of coloring agent and aqueous polymer in immediate-release coating powder actually can directly affect drug product release.