Thermally Conductive Excipient Expands KinetiSol® Processing Capabilities.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Amorphous solid dispersions (ASDs) enhance drug solubility and bioavailability.
• The KinetiSol process uses high-energy mixing to create ASDs.
• Elevated temperatures during processing can lead to drug degradation.

Purpose of the Study:

• To investigate the effect of a thermally conductive excipient (TCE) on the KinetiSol process.
• To determine if TCE incorporation allows for prolonged mixing at a steady-state temperature.
• To enable ASD formation at temperatures below drug degradation thresholds.

Main Methods:

• Incorporation of candurin (a TCE) into ternary drug-polymer-TCE compositions.
• Processing these compositions using the KinetiSol high-energy mixing technique.
• Analysis of thermal conductivity, molecular structure (solid-state NMR), and processing temperatures.

Main Results:

• TCE incorporation significantly increased the thermal conductivity of the compositions.
• Compositions with TCE maintained a steady-state processing temperature within ±5°C of the target.
• Prolonged mixing times were achieved at stable temperatures without drug degradation.
• Solid-state NMR confirmed no impact on drug-polymer molecular structure or mixing.

Conclusions:

• Thermally conductive excipients effectively modify composition thermal properties for the KinetiSol process.
• TCEs enable controlled heat dissipation, facilitating prolonged mixing at lower, stable temperatures.
• This approach allows for the formation of high-performance ASDs without chemical degradation, enhancing drug product development.