OBJECTIVE: To compare the bioavailability of two 15mg ambroxol lozenges with a commercial 30mg ambroxol tablet. DESIGN: Open-label, two-way crossover study. METHOD: Each formulation was randomly administered to 20 healthy Thai volunteers (ten male and ten female) with a 1-week washout period between formulations. After administration, serial blood samples were collected over a 24-hour period and the plasma concentration of ambroxol was subsequently measured using high performance liquid chromatography with ultraviolet detection after liquid-liquid extraction. Pharmacokinetic parameters were analysed by a noncompartmental pharmacokinetic model and compared between formulations using analysis of variance with a significance level of 0.05. RESULTS: The point estimates (90% CI) of the area under the plasma concentration-time curve (AUC) and peak plasma concentration (C(max)) ratios between lozenge and commercial tablet were 1.07 (0.89 to 1.28) and 1.20 (1.04 to 1.40), respectively. The point estimate (90% CI) of the difference between formulations for time to C(max) was 0.40 (-0.20 to 1.00). CONCLUSION: The two formulations under test were not bioequivalent based on the stipulated bioequivalence criteria. The bioavailability from the ambroxol lozenge might be better, since the 90% CI of the AUC(0-infinity) fell outside the bioequivalence range, and its range was narrower. The difference in rate of absorption was not conclusive because ambroxol was delivered from the lozenge by two parallel processes, namely absorption via oral and gastrointestinal mucosa. The additional oral mucosal absorption might not only contribute more absorption but also introduce variability compared with that of tablet administration. The relative importance of oral versus gastrointestinal mucosal absorption of ambroxol from the lozenge formulation, and the clinical significance of this, requires further study.
RCT Entities:
OBJECTIVE: To compare the bioavailability of two 15mg ambroxol lozenges with a commercial 30mg ambroxol tablet. DESIGN: Open-label, two-way crossover study. METHOD: Each formulation was randomly administered to 20 healthy Thai volunteers (ten male and ten female) with a 1-week washout period between formulations. After administration, serial blood samples were collected over a 24-hour period and the plasma concentration of ambroxol was subsequently measured using high performance liquid chromatography with ultraviolet detection after liquid-liquid extraction. Pharmacokinetic parameters were analysed by a noncompartmental pharmacokinetic model and compared between formulations using analysis of variance with a significance level of 0.05. RESULTS: The point estimates (90% CI) of the area under the plasma concentration-time curve (AUC) and peak plasma concentration (C(max)) ratios between lozenge and commercial tablet were 1.07 (0.89 to 1.28) and 1.20 (1.04 to 1.40), respectively. The point estimate (90% CI) of the difference between formulations for time to C(max) was 0.40 (-0.20 to 1.00). CONCLUSION: The two formulations under test were not bioequivalent based on the stipulated bioequivalence criteria. The bioavailability from the ambroxol lozenge might be better, since the 90% CI of the AUC(0-infinity) fell outside the bioequivalence range, and its range was narrower. The difference in rate of absorption was not conclusive because ambroxol was delivered from the lozenge by two parallel processes, namely absorption via oral and gastrointestinal mucosa. The additional oral mucosal absorption might not only contribute more absorption but also introduce variability compared with that of tablet administration. The relative importance of oral versus gastrointestinal mucosal absorption of ambroxol from the lozenge formulation, and the clinical significance of this, requires further study.
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