Experimental characterization and modeling of twin‐screw extruder elements for pharmaceutical hot melt extrusion

Abstract

In this study we characterized various screw elements of a co-rotating twin-screw extruder used for pharmaceutical hot melt extrusion (HME) and measured the pressure characteristic, i.e., the correlation between the axial pressure gradient and the material throughput in a completely filled screw section at different screw speeds. A typical HME matrix material, Soluplus, was used for the experiments and its required rheological properties were determined. A three-parameter model based on a dimensionless formulation of the measured quantities was used. These parameters could not be determined uniquely by fitting to experimental data. Therefore we developed an approach to approximate one empirical parameter based on the mechanistic consideration of a pressure-driven channel flow. The model was extended to account for the variable melt temperature. The results confirmed the expected tendencies and established an essential input parameter set for one-dimensional simulations of co-rotating twin-screw extruders.

An Overview of Pharmaceutical Manufacturing for Solid Dosage Forms

“…Simplified model approaches are still of interest, since they can yield approximate insights into the entire HME process. For example, a one-dimensional (1D) flow model can be applied to different types of screw elements with a typical polymer used in pharmaceutical HME [145,146]. However, more advanced approaches are needed to capture the full complexity of HME and IM.…”

Process Simulation and Data Modeling in Solid Oral Drug Development and Manufacture

“…The term z(x,y(·)) represents the control optimal solution for a system with a time delay as obtained from the LQR technique, where N is a symmetric positive definite matrix, B is a constant matrix, P is a symmetric positive matrix, D(s) is a solution to the Generalized Riccati Equations and y(Àτ) ¼ x (t À τ). Additional details pertaining to the LQR technique can be found in the literature [143][144][145]. The flexibility index problem can be formulated similarly, as shown in Eq.…”

“…Model creation requires experimental data; Incorrect calculation of variance affects loadings [135][136][137][138][139][140][141][142][143][144][145][146][147][148][149][150][151][152] Optimization Methodologies for the Production of Pharmaceutical Products…”

“…More recently these methods have also been used to characterize and optimize formulations of solid dose products [144,145,171]. and explain the use of latent variable methods to enable in silico design of new product formulations.…”

Polymeric formulations for drug release prepared by hot melt extrusion: application and characterization

“…Today, extruders allow inline monitoring and control of the process parameters such as temperature, melt pressure, screw speed, torque, feed rate, and so on. Besides monitoring of various extrusion process conditions, various modeling approaches that can improve the understanding of the mechanisms behind the HME process and thus decrease trial and error efforts have been investigated [13,14]. The melt pressure largely depends on the temperature, feed rate, screw speed, polymer viscosity and miscibility of polymer, drug and other excipients [2].…”