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

IF 1.6 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

{"title":"Bioequivalence Study of Ibuprofen and Diphenhydramine Hydrochloride mini liquid-filled capsules: A Size Reduction Alternative","authors":"David J. Wyatt , Mako Araga , Natali McCloskey , Richard Petruschke , Marianna Armogida MD","doi":"10.1016/j.curtheres.2025.100779","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objective</h3><div>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.</div></div><div><h3>Method</h3><div>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<sub>max</sub>, AUC<sub>0-t</sub>, AUC<sub>0-inf</sub>) for ibuprofen and diphenhydramine. Secondary endpoints were t<sub>max</sub>, t<sub>1/2</sub>, Cl/F, V<sub>z</sub>/F, and λ<sub>Z</sub>. Safety assessments covered adverse events, lab results, and physical exams.</div></div><div><h3>Results</h3><div>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<sub>max</sub> values for test and reference products were comparable, with a median t<sub>max</sub> 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<sub>0-t</sub>, AUC<sub>0-inf</sub>, and C<sub>max</sub>) 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100779"},"PeriodicalIF":1.6000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Therapeutic Research-clinical and Experimental","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0011393X25000049","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

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

期刊介绍： We also encourage the submission of manuscripts presenting preclinical and very preliminary research that may stimulate further investigation of potentially relevant findings, as well as in-depth review articles on specific therapies or disease states, and applied health delivery or pharmacoeconomics. CTR encourages and supports the submission of manuscripts describing: • Interventions designed to understand or improve human health, disease treatment or disease prevention; • Studies that focus on problems that are uncommon in resource-rich countries; • Research that is "under-published" because of limited access to monetary resources such as English language support and Open Access fees (CTR offers deeply discounted English language editing); • Republication of articles previously published in non-English journals (eg, evidence-based guidelines) which could be useful if translated into English; • Preclinical and clinical product development studies that are not pursued for further investigation based upon early phase results.