Dissolution efficiency and bioequivalence study using urine data from healthy volunteers: a comparison between two tablet formulations of cephalexin

The aim of the present study was to assess the bioequivalence of two cephalexin tablet formulations available in the Brazilian market (product A as reference formulation and product B as test formulation). Dissolution efficiency (DE%) was calculated for both formulations to evaluate their in vitrobiopharmaceutical features. The oral bioequivalence study was performed in twenty-four healthy volunteers in a crossover design. Single oral dose (tablet containing 500 mg of cephalexin) of each product was administered with two weeks of washout period. Urinary concentrations of cephalexin were measured by high-performance liquid chromatography (HPLC) method and pharmacokinetics parameters were estimated by urinary excretion data. The bioequivalence was determined by the following parameters: the cumulative amount of cephalexin excreted in the urine, the total amount of cephalexin excreted in the urine and the maximum urinary excretion rate of cephalexin. DE values of immediate-release cephalexin tablets (500 mg) were 68.69±4.18% for product A and 71.03±6.63% for product B. Regarding the dissolution test of the two brands (A and B) analysed, both were in compliance with the official pharmacopeial specifications, since the dissolution of both formulations was superior to 80% of the amount declared in the label after 45 minutes of test (A=92.09%±1.84; B=92.84%±1.08). The results obtained indicated that the products A and B are pharmaceutical equivalents. Confidence intervals for the pharmacokinetic parameters were in compliance with the international standards, indicating that products A and B can be considered bioequivalents and, therefore, interchangeable.本研究旨在评估巴西市场在售的两种头孢氨苄片剂制剂的生物等效性，其中制剂A作为参比制剂，制剂B作为受试制剂。研究通过计算两种制剂的溶出度效率（Dissolution Efficiency, DE%），以评价其体外生物药剂学特性。本口服生物等效性研究采用交叉设计，纳入24名健康志愿者。受试者单次口服给予每款制剂（含500mg头孢氨苄的片剂），两次给药间隔两周的洗脱期。采用高效液相色谱法（high-performance liquid chromatography, HPLC）测定尿液中的头孢氨苄浓度，并通过尿液排泄数据估算药代动力学参数。本研究通过以下参数判定生物等效性：尿液中累积排泄的头孢氨苄量、尿液中总排泄的头孢氨苄量，以及头孢氨苄的最大尿排泄速率。500mg即释型头孢氨苄片剂的溶出度效率值：制剂A为68.69±4.18%，制剂B为71.03±6.63%。针对本次分析的两个品牌（A与B）的溶出试验结果显示，两种制剂均符合官方药典标准：试验进行45分钟后，两种制剂的溶出度均高于标签标示量的80%（制剂A为92.09%±1.84；制剂B为92.84%±1.08）。研究结果表明，制剂A与制剂B为药学等效制剂。药代动力学参数的置信区间符合国际标准，提示制剂A与制剂B可被视为生物等效制剂，因此二者可互换使用。