Indomethacin sustained-release suppositories containing sugar ester in polyethylene glycol base

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems

Background:

• Indomethacin (IM) is a nonsteroidal anti-inflammatory drug often requiring sustained-release formulations for optimal therapeutic effect.
• Conventional dosage forms may lead to fluctuating plasma levels and suboptimal patient compliance.

Purpose of the Study:

• To develop and evaluate sustained-release suppositories of indomethacin (IM) using sugar ester and polyethylene glycol 4000 (PEG).
• To investigate the release kinetics and in vivo absorption profile of the developed suppositories.

Main Methods:

• Indomethacin suppositories were prepared using the fusion method with varying sugar ester and PEG 4000 concentrations.
• In vitro release testing was performed to assess drug release rates.
• X-ray diffraction was used to analyze the physical state of indomethacin within the suppository matrix.
• In vivo absorption studies were conducted in rabbits to evaluate plasma drug concentrations over time.

Main Results:

• X-ray analysis confirmed that indomethacin existed in an amorphous state within the PEG-base suppositories.
• Suppositories containing 60% sugar ester exhibited optimal slow-release characteristics.
• In vivo absorption tests in rabbits showed well-sustained indomethacin plasma levels.
• A strong correlation was observed between in vitro release data and in vivo absorption profiles.

Conclusions:

• Sustained-release suppositories formulated with sugar ester and PEG 4000 effectively deliver indomethacin.
• The amorphous state of indomethacin in the suppository matrix enhances rectal release and absorption, particularly in a low-volume rectal environment.
• The Higuchi model adequately describes the drug release mechanism, indicating matrix-controlled release.