Pharmacokinetics and bioavailability of single dose ibuprofen and pseudoephedrine alone or in combination: a randomized three-period, cross-over trial in healthy Indian volunteers

Objective: To compare the bioavailability of single dose ibuprofen 200 mg and pseudoephedrine hydrochloride 30 mg administered alone or in combination as an oral suspension. Methods: This was a single-center, randomized, single-dose, open-label, 3-period, crossover study. After an overnight fast (≥10 h), 18 healthy male subjects received either ibuprofen 200 mg (reference-A), pseudoephedrine 30 mg (reference-B) or the combination (test-C) as a suspension, on 3 separate visits, with blood sampling up to 36-h post-dose. The primary pharmacokinetic parameters, maximum plasma concentration (C(max)) and area under the plasma concentration–time curve (AUC) from time zero to last measurable concentration (AUC(0−t)) and extrapolated to infinity (AUC(0−∞)) were compared by an analysis of variance using log-transformed data. Bioequivalence was concluded if the 90% confidence intervals (CIs) of the adjusted geometric mean (gMean) ratios for C(max) and AUC were within the predetermined range of 80–125%, in accordance with regulatory requirements. Results: For the test formulation, the ibuprofen gMean C(max) was 17.0 μg/mL (vs. 18.1 μg/mL for reference-A), AUC(0−t) was 57.1 (vs. 60.0 μg·h/mL), and AUC(0−∞) was 59.9 μg·h/mL (vs. 63.1 μg·h/mL). The 90% CIs for the ratio (test/reference-A) were 81.0–108.1% for C(max), 91.5–98.4% for AUC(0−t) and 91.6–97.9% for AUC(0−∞). For pseudoephedrine, the gMean C(max) for the test formulation was 97.2 ng/mL (vs. 98.5 ng/mL for reference-B), AUC(0−t) was 878.4 (vs. 842.8 ng·h/mL) and AUC(0−∞) was 907.8 ng·h/mL (vs. 868.3 ng·h/mL). The 90% CIs for the ratio (test/reference-B) were 92.4–106.9% for C(max), 97.7–111.0% for AUC(0−t) and 97.9–111.3% for AUC(0−∞). All treatments were well tolerated. Conclusion: This oral suspension containing ibuprofen and pseudoephedrine combined in a new formulation met the regulatory criterion for bioequivalence compared with oral suspensions containing the individual components.