Wyatt David J, Araga Mako, McCloskey Natali, Petruschke Richard, Armogida Marianna
Clinical Pharmacology and Bioanalysis, Syneos Health Clinical Research Services, Miami, Florida.
Haleon, Warren, New Jersey.
Curr Ther Res Clin Exp. 2025 Feb 12;102:100779. doi: 10.1016/j.curtheres.2025.100779. eCollection 2025.
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.
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.
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, AUC, AUC) for ibuprofen and diphenhydramine. Secondary endpoints were t, t, Cl/F, V/F, and λ. Safety assessments covered adverse events, lab results, and physical exams.
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 values for test and reference products were comparable, with a median t 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, AUC, and C) 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.
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.
Advil PM液状软胶囊被广泛用于改善因疼痛而睡眠障碍的个体的生活质量。为了满足那些吞咽传统胶囊有困难的人群的需求，研发了Advil PM液状软胶囊迷你装，这是一种较小的胶囊变体，其成分（布洛芬/盐酸苯海拉明200毫克/25毫克）与原始的Advil PM液状软胶囊相同，是一种更易于服用的替代品。
在空腹条件下，确定新的尺寸减小的Advil PM液状软胶囊迷你装（试验品）与目前市场上销售的Advil PM液状软胶囊（参比品）的生物等效性。
这项I期研究是一项随机、开放标签、双治疗、双序列、双周期交叉试验。受试者接受单剂量的试验品或参比品，中间间隔7天的洗脱期。主要终点包括布洛芬和苯海拉明的药代动力学参数（Cmax、AUC0-t、AUC0-∞）。次要终点是t1/2、tmax、Cl/F、V/F和λz。安全性评估包括不良事件、实验室检查结果和体格检查。
44名受试者被随机分组，42名完成了布洛芬两个治疗周期，41名完成了苯海拉明两个治疗周期。该人群在年龄、体重指数和性别方面均衡，主要为西班牙裔/拉丁裔。试验品和参比品Cmax的平均值具有可比性，苯海拉明（试验品和参比品）的tmax中位数为3小时，布洛芬的tmax分别为1小时（试验品）和0.875小时（参比品）。所有药代动力学（PK）参数（AUC0-t、AUC0-∞和Cmax）的几何平均比值（90%CI），布洛芬分别为99.15%（96.76-101.61）、99.20%（96.82-101.63）和95.13%（88.31-102.47）；苯海拉明分别为102.62%（98.15-107.30）、102.73%（98.31-107.34）和102.51%（93.54-112.35）。所有数值均在80%-125%的生物等效性接受标准范围内。未报告严重不良事件，受试者对两种制剂的吞咽便利性评价均为正面。
新的Advil PM液状软胶囊迷你装制剂与市售的Advil PM液状软胶囊具有生物等效性。较小的胶囊尺寸可能为吞咽困难的个体提供更方便的选择，而不会影响药物的疗效或安全性。
