Comparative Pharmacokinetics of Two Fast-Dissolving Oral Ibuprofen Formulations and a Regular-Release Ibuprofen Tablet in Healthy Volunteers

Abstract and Introduction

Abstract

Objective: Spalt-Liqua® is a newsoft gelatin capsule containing 200mg of totally dissolved ibuprofen as the active ingredient. The primary objective of the study was to assess bioequivalence between the new ibuprofen formulation and the standard 200mg sugar-coated tablets. The secondary objective was to assess bioequivalence between the new formulation and 200mg tablets of a fast-dissolving ibuprofen lysinate formulation.
Design and Study Participants: A single oral dose of ibuprofen 400mg (two of each type of capsule or tablet) was administered to 26 healthy male volunteers in a nonblind, randomised, three-way crossover study with a 6-day washout interval between each drug administration period.
Main Outcome Measures and Results: For the soft gelatin capsules, maximum concentration (C_max) was significantly greater and time to reach maximum concentration (t_max) was significantly shorter in comparison with the reference tablet formulation, and therefore bioequivalence for these parameters could not be confirmed. However, the shorter absorption time and higher peak plasma concentration did not affect the extent of absorption of the soft gelatin capsule. In contrast to this result, the pharmacokinetic profile of the soft gelatin capsules was very similar to that of the fast-dissolving ibuprofen lysinate tablets. The 90% confidence intervals for logarithmically transformed C_max and areas under the drug concentration-time curve from zero to the time of the last measurable concentration (AUC_t) and to infinity (AUC_infinity ) were within the required bioequivalence range. The three formulations were well tolerated and no clinically significant adverse events were observed.
Conclusions: In accordance with previous results, this study confirmed the pharmacokinetic differences between a standard ibuprofen tablet formulation and fast-dissolving formulations.

Introduction

Ibuprofen is a nonsteroidal anti-inflammatory drug that displays potent anti-inflammatory properties as well as strong analgesic and anti-pyretic activity. After its first registration as an antirheumatic drug in 1969 in the UK, it was widely used as a prescription-only medicine.^[1] In 1983 it became available without prescription and currently it is used throughout the world as an over-the-counter medicine for the treatment of pain and fever. The recommended single dose of ibuprofen for the treatment of mild to moderate pain is 200 to 400mg with a maximum daily dosage of 1200mg, compared with a daily dosage of up to 3600mg for the treatment of rheumatic disease.

After oral administration of regular-release tablet preparations, ibuprofen is almost completely absorbed from the gastrointestinal tract.^[2] Peak serumconcentrations and maximal analgesic effect normally occur within 1 to 2 hours of administration, and the plasma half-life is approximately 2 hours. Different brands of regular-release tablets may, however, show great differences in pharmacokinetic behaviour due to different galenical formulations, which has been demonstrated on several occasions.^[3]

In comparison with standard ibuprofen tablet formulations, which contain the active ingredient as the free acid, liquid formulations or faster dissolving ibuprofen salts (e.g. lysine or arginine salts) demonstrate faster absorption and higher peak serum concentrations.^[4]

The primary objective of this study was to assess bioequivalence between a new ibuprofen soft gelatin capsule formulation and the standard 200mg sugar-coated tablets. This patented new formulation contains totally dissolved ibuprofen and was developed to show the same advantages as described above for liquid or fast-dissolving formulations. The secondary objective of the study was to assess bioequivalence between the new soft gelatin capsule formulation and a fast-dissolving ibuprofen lysinate formulation.

Clin Drug Invest. 2001;21(1) © 2001  Adis International Limited

Cite this: Comparative Pharmacokinetics of Two Fast-Dissolving Oral Ibuprofen Formulations and a Regular-Release Ibuprofen Tablet in Healthy Volunteers - Medscape - Jan 01, 2001.