相似因子法评价替米沙坦氢氯噻嗪片自研制剂与原研制剂溶出曲线的相似性

Similarity Evaluation of Dissolution Curves of Self-made and Original Telmisartan/Hydrochlorothiazide Tablets by the f_2 Factor Method

目的考察替米沙坦氢氯噻嗪片自研制剂与原研制剂溶出曲线的相似性,为自研制剂的处方和工艺筛选以及与原研制剂的质量一致性比较提供依据。方法采用高效液相色谱法,色谱柱为Welch Ultimate XB-C_8(4.6 mm×250 mm,5μm),以磷酸二氢铵溶液(取磷酸二氢铵2.0 g,加水1 L使溶解,用磷酸调节pH值至3.0)为流动相A,乙腈-甲醇(50∶50)为流动相B,进行梯度洗脱,流速为1.2 mL·min^(-1),检测波长为270 nm,进样量为20μL,测定自研制剂与原研制剂中替米沙坦和氢氯噻嗪在4种不同的溶出介质中的溶出曲线,采用相似因子法对溶出曲线的相似度进行评价。结果在不同的溶出介质中,替米沙坦氢氯噻嗪片自研制剂与原研制剂的溶出曲线均符合f_2≥50或15 min溶出量≥85%,可认为两者具有相似性。结论自研制剂与原研制剂的溶出行为基本一致,初步说明自研制剂的处方和工艺具有合理性和可行性。

OBJECTIVE To explore the similarity of the dissolution curves of self-made and original telmisartan/hydrochlorothiaz- ide tablets and provide basis for the prescription and process screening of self-made preparation and the quality similarity evaluation with original preparation. METHODS The dissolution curves of telmisartan and hydrochlorothiazide from self-made and original prep- arations in four different dissolution media were determined using HPLC. The HPLC method was performed on Welch Ultimate XB-Cs column （4. 6 mmx 250 ram, 5 μm） with mobile phase A consisting of ammonium dihydrogen phosphate solution （2. 0 g ammonium all- hydrogen phosphate was dissolved in 1 L water then adjusted to pH 3.0 with phosphoric acid） and mobile phase B consisting of acetoni- trile-methanol （50： 50） at a flow rate of 1.2 mL · min-1. The detection wavelength was set at 270 nm. The injection volume was 20 μL. Then f2 factor method was used to evaluate the similarity. RESULTS The dissolution curves of self-made and original prepara- tions of telmisartan/hydroehlorothiazide tablets in different dissolution media showed similarity, with thef2 factor 〉50 or the dissolution rate within 15 min〉85%i CONCLUSION The dissolution behaviors of self-made and original telmisartan/hydrochlorothiazide tab- lets are basically similar, whieh indicates that the prescription and technology of self-made preparation are reasonable and feasible.