Revealing Polymorphic Phase Transformations in Polymer-Based Hot Melt Extrusion Processes

• DOI: 10.1021/acs.cgd.7b01374
• Publication Date: 2018-03-09T20:15:57Z
• Authors: José R. Hernández...; Vilmalí López-Mejías; Torsten Stelzer
• Keywords: 03 medical and health sciences; 0302 clinical medicine

The inadvertent occurrence of polymorphic phase transformations in active pharmaceutical ingredients (APIs) during hot melt extrusion (HME) processes has been claimed to limit the application this technique. Hence, control polymorphism would need be addressed if there is any prospect HME successfully implemented as an alternative solid dosage formulation strategy integrated, continuous end-to-end manufacturing settings. This work demonstrates that flufenamic acid (FFA), one most APIs known, thus far, can processed using temperature-simulated with polyethylene glycol (PEG) polymeric carrier. At temperatures above transition point FFA forms III and I (42 °C), induction time transformation longer than average reported residence conventional (5 min). Moreover, it was demonstrated thorough understanding thermodynamic kinetic design space for PEG-FFA system leads produced crystalline dispersions. Ultimately, investigation helps gain fundamental processing needs dispersions, which will lead broader a drug products containing prone polymorphism, representing about 80% all APIs.