Rational Design of Multicomponent Polymeric Systems Based on a Transient Plasticization Window for Hot-Melt Extrusion

Background: Hot-melt extrusion (HME) is a promising technology for the manufacturing of drug products; however, its application is limited by elevated thermal and shear stresses that may induce degradation of thermolabile active pharmaceutical ingredients. One of the approaches to reducing processing temperatures is the use of polymeric systems with tailored thermal and rheological properties. The aim of the study was to develop an approach for the design of polymeric systems exhibiting a transient plasticization window, enabling a reduction in melt viscosity and improved processability under low-temperature extrusion conditions, followed by the formation of a structurally coherent matrix upon cooling. Methods: The compatibility of the initial polymers was assessed using laser microinterferometry. Based on the obtained data, three- and four-component polymeric compositions were designed and prepared by hot-melt extrusion. The resulting materials were characterized by differential scanning calorimetry, melt rheology analysis, and storage stability assessment. Thermal and rheological data were used to iteratively optimize the polymeric systems. Results: A four-component polymeric system based on PVP K-29/32, PEG 400, PEG 1500, and HPC EF was developed, suitable for processing by hot-melt extrusion at 70 °C. The final system enabled formation of a homogeneous extrudate, exhibited reproducible rheological behavior, and remained stable in the solid-state during storage, with no evidence of cold flow. Conclusions: It was established that, in the design of polymeric systems for hot-melt extrusion, the key factor is not achieving the lowest possible glass transition temperature, but rather the design of a system in which viscosity is transiently reduced under processing conditions and followed by structural stabilization upon cooling. The proposed approach may be applied in the development of polymeric premixes for the preparation of dosage forms by hot-melt extrusion, including those incorporating thermolabile active pharmaceutical ingredients.