THEDES as a drug product intermediate for improved melt-extrusion processibility of thermally labile active ingredients

Abstract

Hot melt extrusion (HME) is extensively employed in the pharmaceutical industry, but its utilization of heat raises concerns over drugs’ thermal stability. Strategies to improve stability and processibility of thermolabile materials via salt formation and co-crystals engineering are found in the literature. In this work, it was attempted to use therapeutic deep eutectic solvents (THEDES) as a mean to achieve improved drug thermal stability through the formation of a charge-assisted strong hydrogen boding network. Thermogravimetric studies on THEDES formed using a thermolabile drug, lidocaine, with different non-steroidal anti-inflammatory agents (NSAIDs) were employed to test this hypothesis. The resulted three THEDESs in this study were all tested to be more thermally stable than the corresponding parent compounds, confirming the stabilizing effect from the THEDES bonding network. This investigation reintroduces THEDES as a drug product intermediate with improved processibility for HME.

Keywords

• hot melt extrusion
• therapeutic deep eutectic solvents
• thermal stability
• tga