布洛芬与盐酸苯海拉明微型液体胶囊的生物等效性研究：缩小尺寸的选择

IF 1.5 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental Pub Date : 2025-01-01 DOI:10.1016/j.curtheres.2025.100779

David J. Wyatt , Mako Araga , Natali McCloskey , Richard Petruschke , Marianna Armogida MD

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引用次数: 0

摘要

vil PM液体凝胶被广泛用于改善因疼痛而睡眠障碍的个人的生活质量。为了适应那些吞咽传统胶囊有困难的人，Advil PM液体凝胶Minis是一种更小的胶囊变体，含有与原始Advil PM液体凝胶相同的成分（布洛芬/盐酸苯海拉明200毫克/25毫克），是一种更易于管理的替代品。目的在禁食条件下，与目前上市的Advil PM liquid - gel（参比）产品相比，建立新的缩小尺寸Advil PM liquid - gel mini（试验）的生物等效性。方法本研究采用随机、开放标签、两治疗、两序列、两期交叉试验。受试者接受单剂量试验产品或参考产品，间隔7天洗脱期。主要终点包括布洛芬和苯海拉明的PK参数（Cmax, AUC0-t, AUC0-inf）。次要终点为tmax、t1/2、Cl/F、Vz/F和λZ。安全性评估包括不良事件、实验室结果和身体检查。结果随机抽取44例受试者，42例完成布洛芬治疗期，41例完成苯海拉明治疗期。人口在年龄、BMI和性别上是平衡的，主要是西班牙裔/拉丁裔。试验品和参比品的平均Cmax值具有可比性，苯海拉明（试验品和参比品）的tmax中位数为3小时，布洛芬（试验品）的tmax中位数为1小时，对照品为0.875小时。布洛芬各药代动力学参数AUC0-t、AUC0-inf和Cmax的几何平均比值（90% CI）分别为99.15%（96.76 ~ 101.61）、99.20%（96.82 ~ 101.63）和95.13%(88.31 ~ 102.47)，苯海拉明的几何平均比值（90% CI）分别为102.62%（98.15 ~ 107.30）、102.73%（98.31 ~ 107.34）和102.51%（93.54 ~ 112.35）。所有值均在80%-125%的生物等效性接受标准范围内。没有严重的不良事件报告，受试者对两种配方的吞咽容易度评价都是积极的。结论新制剂与市售Advil PM液体凝胶具有生物等效性。较小的胶囊尺寸可能为吞咽困难的个人提供更方便的选择，而不会影响药物的功效或安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Bioequivalence Study of Ibuprofen and Diphenhydramine Hydrochloride mini liquid-filled capsules: A Size Reduction Alternative

Background

Advil PM Liqui-Gels are widely used to improve the quality of life for individuals experiencing sleep disturbances due to pain. To accommodate those who have difficulty swallowing traditional capsules, Advil PM Liqui-Gels Minis, a smaller capsule variant containing the same composition (ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg) as the original Advil PM Liqui-Gels, was developed as a more manageable alternative.

Objective

Establish the bioequivalence of new size-reduced Advil PM Liqui-Gels Minis (test) compared to the currently marketed Advil PM Liqui-Gels (reference) product under fasting conditions.

Method

This Phase I study was a randomized, open-label, two-treatment, two-sequence, two-period crossover trial. Subjects either received a single dose of test or reference product, separated by a 7-days washout period. Primary endpoints included PK parameters (C_max, AUC_0-t, AUC_0-inf) for ibuprofen and diphenhydramine. Secondary endpoints were t_max, t_1/2, Cl/F, V_z/F, and λ_Z. Safety assessments covered adverse events, lab results, and physical exams.

Results

Forty-four subjects were randomized, 42 completed both treatment periods for ibuprofen and 41 for diphenhydramine. The population was balanced in age, BMI, and gender, predominantly Hispanic/Latino. Mean C_max values for test and reference products were comparable, with a median t_max of 3 hours for diphenhydramine (both test and reference) and 1 hour (test) and 0.875 hour (reference) for ibuprofen. The geometric mean ratios (90% CI) for all pharmacokinetic (PK) parameters (AUC_0-t, AUC_0-inf, and C_max) were 99.15% (96.76–101.61), 99.20% (96.82–101.63) and 95.13% (88.31–102.47), respectively, for ibuprofen, and 102.62% (98.15–107.30), 102.73% (98.31–107.34), and 102.51% (93.54–112.35), respectively, for diphenhydramine. All values fell within the bioequivalence acceptance criteria of 80%–125%. No serious adverse events were reported, and subjects rated the ease of swallowing positively for both formulations.

Conclusion

The new Advil PM Liqui-Gels Minis formulation is bioequivalent to the marketed Advil PM Liqui-Gels. The smaller capsule size may offer a more convenient option for individuals with swallowing difficulties, without compromising the drug's efficacy or safety.

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来源期刊

Current Therapeutic Research-clinical and Experimental 医学-药学

CiteScore

3.50

自引率

0.00%

发文量

审稿时长

3 months

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