Bioavailability of indomethacin from two multiple-units controlled-release formulations

Area of Science:

• Pharmacology
• Pharmaceutical Technology
• Drug Delivery Systems

Background:

• Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammation.
• Standard indomethacin capsules can cause gastrointestinal and central nervous system side effects due to fluctuating drug concentrations.
• Controlled-release formulations aim to provide a more stable drug release profile, potentially improving tolerability.

Purpose of the Study:

• To evaluate the bioequivalence of two multiple-unit, controlled-release indomethacin capsule formulations with enteric-coated pellets compared to a standard capsule.
• To assess the in vitro dissolution profiles and in vivo absorption rates of the novel formulations.

Main Methods:

• A crossover study was conducted with normal human subjects.
• In vitro dissolution testing was performed at pH 6.5 and 7.5.
• Plasma indomethacin concentrations were measured over time to determine pharmacokinetic parameters.

Main Results:

• Both controlled-release formulations were bioequivalent to the standard capsule in terms of overall bioavailability.
• In vitro dissolution rates were slower for the enteric-coated pellet formulations compared to the standard capsule.
• In vivo, absorption rates decreased in the order: standard capsule > formulation I > formulation II, correlating with dissolution rates.

Conclusions:

• Multiple-unit controlled-release indomethacin formulations offer a reliable and reproducible drug source.
• These formulations may reduce peak drug concentrations, potentially leading to better patient tolerance and fewer side effects.