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

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_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.

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.

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.