Melt viscosity is an essential property in pharmaceutical processes such as mixing, extrusion, fused deposition modeling, and melt coating. Measuring and modeling of the melt viscosity for drug/polymer mixtures is essential for optimization of the manufacturing process. In this work, the melt viscosity of nine formulations containing the drug substances acetaminophen, itraconazole, and griseofulvin, as well as the pharmaceutical polymers Eudragit EPO, Soluplus, and Plasdone S-630, were analyzed with a rotational and oscillatory rheometer. The shear rate, temperature, and drug fraction were varied systematically to investigate their influence on viscosity. The results for the pure polymers showed typical shear-thinning behavior and are fundamental for modeling with the Carreau and Arrhenius approaches. The investigations of the viscosity of the drug/polymer mixtures resulted in a plasticizing or a filler effect, depending on the type of drug and the phase behavior. A drug shift factor was proposed to model the change in viscosity as a function of the drug fraction. On this basis, a universal model to describe the melt viscosity of drug/polymer mixtures was developed, considering shear rate, temperature, and drug fraction.

Background/Objective: Hot-melt extrusion has been established as a formulation strategy for various pharmaceutical applications. However, tailoring the screw configuration is a major challenge where 1D modeling is utilized. This usually requires specific screw parameters, which are rarely noted in the literature, especially when dealing with shear-thinning formulations. Methods: Therefore, a custom-made test rig was used to assess the behavior of various conveying and kneading elements using Newtonian silicon oil and shear-thinning silicon rubber. The pressure and the power were measured as a function of volume flow. A model was proposed characterizing the screw element behavior by six individual parameters $\left({\mathrm{A}}_1, {\mathrm{A}}_2, {\mathrm{A}}_3, {\mathrm{B}}_1, {\mathrm{B}}_2, {\mathrm{B}}_3\right)$. Results: The experimental results regarding the behavior with respect to Newtonian fluids were in good agreement with the literature and were modeled in accordance with the Pawlowski approach. In terms of shear-thinning fluids, the influence of screw speed on pressure and power was quantified. An evaluation framework was proposed to assess this effect using two additional parameters. Based on a high number of repetitive measurements, a confidence interval for the individual screw parameters was determined that is suitable to highlight the differences between element types. Conclusions: Finally, geometrical screw parameters for Newtonian and shear-thinning flow were assessed and modeled, with three conveying and three kneading elements characterized.

Background/Objectives: Copovidone (polyvinylpyrrolidone-vinyl acetate copolymer, PVP/VA) is a widely used pharmaceutical excipient with various applications in drug formulation. In hot melt extrusion (HME), PVP/VA is an approved carrier material for the production of amorphous solid dispersions (ASDs) by embedding drugs on a molecular level. This study investigates the properties and processability of two copovidone grades—Plasdone™ S-630 (PS-630) and the novel Plasdone™ S-630 Ultra (PS-630U)—to assess their suitability as ASD carrier materials. Methods: The thermal and physicochemical characteristics of both polymers were evaluated, focusing on glass transition temperature and polymer melt rheology. The process performance in HME was investigated on small-scale as well as in production-scale extrusion. The two model drugs itraconazole and griseofulvin were used to examine drug dissolution and degradation during HME via in-line UV-vis spectroscopy. Results: When comparing both polymers, PS-630U offers various advantages due to the improved powder feeding behavior and reduced yellowing of extruded products while maintaining similar melt properties and drug compatibility compared to PS-630. Conclusions: These findings support the use of PS-630U as an optimized copovidone grade for ASD manufacturing, facilitating improved processing characteristics and best product qualities without the requirement of significant formulation adjustments.

Purpose: Residence time in pharmaceutical hot-melt extrusion is a crucial process parameter affecting the quality attributes of a dosage form such as content uniformity, bioavailability and toxicity. There is a lack of knowledge about the influence of screw element types on the residence time distribution, which will be addressed in this study. Methods: Different conveying and kneading elements will be characterized concerning their effect on the residence time using a co-rotating twin-screw extruder with a 28 mm screw diameter. Tracer experiments will be performed while concentration time profiles are measured via inline UV-Vis spectroscopy. Results: The residence time distribution of all screw types is primarily related to the volume flow but independent of pressure. The two-compartment model of Reitz was utilized to describe the experimental data mathematically. Screw-type-specific dimensionless parameters were derived to quantify the axial mixing performance, as well as the effect on residence time. Conclusions: The influence of different screw elements on the residence time in hot-melt extrusion processes was quantified using a dimensionless mixing volume and a dimensionless axial dispersion coefficient. The results meet the quantitative descriptions from the literature.