Structure based release kinetics analysis of doxazosin mesylate sustained-release tablets using micro-computed...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Drug Delivery

Background:

• Solid dosage form structure critically influences drug release kinetics and performance.
• Understanding internal structure is key for evaluating modified-release formulations.
• Doxazosin mesylate sustained-release tablets require detailed structural analysis for quality control.

Purpose of the Study:

• To assess the 3D structures of doxazosin mesylate sustained-release tablets using micro-computed tomography (micro-CT).
• To investigate the correlation between internal structure and drug release behaviors, particularly under alcohol-induced conditions.
• To compare structural parameters and release profiles of a reference listed drug (RLD) and a generic formulation.

Main Methods:

• Parallel assessment of 3D tablet structures using micro-computed tomography (micro-CT).
• Conventional dissolution testing.
• Alcohol-induced dose-dumping tests in media containing ethanol.
• Analysis of structural parameters including volume and surface area.

Main Results:

• No significant difference in release profiles between RLD and generic formulations in conventional dissolution.
• Generic formulation showed slightly faster release in ethanol media during dose-dumping tests.
• Ethanol accelerated dissolution and altered internal tablet structures, with distinct structural parameter differences (volume, area) between RLD and generic in 40% ethanol.

Conclusions:

• 3D structural data from micro-CT provides valuable insights into unique release behaviors of modified-release formulations.
• Internal fine structure significantly impacts drug release kinetics, especially in the presence of ethanol.
• Structural differences between RLD and generic formulations become apparent under stress conditions, crucial for drug development and quality control.