Insights into the Control of Drug Release from Complex Immediate Release Formulations

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Water transport kinetics into tablets are crucial for controlling drug dissolution and release, particularly for immediate-release formulations.
• Tablet microstructure and formulation composition significantly influence these water transport dynamics.

Purpose of the Study:

• To investigate the impact of tablet porosity and formulation components on water penetration kinetics.
• To correlate water transport with drug dissolution rates using terahertz pulsed imaging.

Main Methods:

• Terahertz pulsed imaging was utilized to monitor water penetration into tablets within a flow cell.
• Tablets with varying porosity (10-20%) and NaCl concentrations (0-20%) were prepared using specific drug formulations.
• A power-law model was applied to analyze liquid penetration data, with factorial analysis used to determine factor significance.

Main Results:

• Tablet porosity was identified as the dominant factor influencing both liquid penetration and dissolution.
• Sodium chloride (NaCl) significantly impacted liquid penetration via osmotic effects and gelling suppression, with diminishing returns above 5-10% loading.
• The presence of spray-dried intermediate limited the release of the active pharmaceutical ingredient (API) during dissolution.

Conclusions:

• Tablet porosity is a critical determinant of water transport and dissolution, offering a primary control point for formulation design.
• NaCl concentration influences water penetration, but its effect plateaus at moderate levels.
• Spray-dried intermediates can modulate API release, providing another formulation strategy for controlling dissolution.