We report for the first time that incorporation of a thermally conductive excipient (TCE) modifies the thermal conductivity of the ternary drug-polymer-TCE compositions such that high-energy mixing can occur for prolonged periods at a selected steady-state temperature during the KinetiSol process. In this study, candurin, a TCE, is incorporated within a composition that is processed by high-energy mixing from the KinetiSol process to increase the thermal conductivity of the ternary composition. The improved thermal conductivity promotes heat transfer and enables the high-energy mixing applied during the KinetiSol process to be continued for prolonged time intervals at a selected steady-state temperature, instead of undergoing a continued increase in temperature when the TCE is not present in the composition. The addition of candurin does not impact the molecular structure and mixing of the drug and polymer in ASDs from solid-state NMR characterizations. Compositions with candurin achieved a steady-state processing temperature with + 5°C of the target temperature, and these compositions demonstrated the ability to mix for prolonged time periods while maintaining within this steady-state temperature range, thus enabling the formation of an ASD at a temperature that the drug does not chemically degrade. This study demonstrated that inclusion of the TCE modified the composition's thermal conductivity to efficiently dissipate heat to achieve a selected steady-state temperature during the KinetiSol process, thus providing prolonged mixing times at a lower temperature for dissolving the drug into the polymer to achieve an ASD without sacrificing product performance.
Keywords: Amorphous solid dispersions; KinetiSol processing; Solubility enhancement; Thermally conductive excipients.