Switch between Cocrystal and Coamorphous Forms Depending on Thermal Modulation of Hot-Melt Extrusion

Area of Science:

• Pharmaceutical Science
• Materials Science
• Green Chemistry

Background:

• Cocrystal (CC) and coamorphous (CM) techniques are green methods to enhance drug solubility and bioavailability.
• Hot-melt extrusion (HME) is a solvent-free, scalable manufacturing technique suitable for CC and CM production.

Purpose of the Study:

• To selectively prepare indomethacin-nicotinamide (IMC-NIC) CC and CM formulations using HME.
• To investigate the formation mechanisms of IMC-NIC CC and CM.
• To evaluate the dissolution and stability of the prepared formulations.

Main Methods:

• Hot-melt extrusion (HME) at varying barrel temperatures (105-150 °C).
• Solid-state Nuclear Magnetic Resonance (SS NMR) spectroscopy.
• Radial Distribution Function (RDF) and binding energy (Ebind) calculations.

Main Results:

• Selective preparation of IMC-NIC CC (105-120 °C) and CM (125-150 °C) was achieved by modulating HME barrel temperature.
• SS NMR, RDF, and Ebind calculations elucidated CC formation via strong heteromeric interactions and ordered structures at lower temperatures, and CM formation via weaker interactions and disordered structures at higher temperatures.
• Both IMC-NIC CC and CM demonstrated improved dissolution and stability compared to crystalline or amorphous IMC.

Conclusions:

• HME offers a simple, environmentally friendly method for tunable CC and CM formulation preparation.
• Barrel temperature is a critical parameter for controlling the molecular arrangement and properties of IMC-NIC formulations.
• The developed strategy provides a flexible approach to enhance drug solubility and stability.