Validation of Model-Based Melt Viscosity in Hot-Melt Extrusion Numerical Simulation

Abstract

A validation for the use of model-based melt viscosity in hot-melt extrusion numerical simulations was presented. Here, the melt viscosity of an amorphous solid dispersion (ASD) was calculated by using its glass transition temperature (Tg) and the rheological flow profile of the pure polymeric matrix. All further required physical properties were taken from the pure polymer. For forming the ASDs, four active pharmaceutical ingredients (APIs), that had not been considered in first place to establish the correlation between Tg and melt viscosity were examined. The ASDs were characterized in terms of density, specific heat capacity, melt rheology, API solubility in the polymeric matrix, and deviation from the Couchman–Karasz fit to, identify the influencing factors of the accuracy of the simulation using model-based melt viscosity. Furthermore, the energy consumption of the hot-melt extrusion (HME) experiments, conventional simulation, and simulation using model-based melt viscosity were compared. It was shown, with few exceptions, that the use of model-based melt viscosity in terms of the HME simulation did not reduce the accuracy of the computation outcome. The commercial one-dimensional (1D) simulation software Ludovic® was used to conduct all of the numerical computation. As model excipients, vinylpyrrolidone-vinyl acetate copolymer (COP) in combination with four APIs (celecoxib, loratadine, naproxen, and praziquantel) were investigated to form the ASDs.

Determining Thermal Conductivity of Small Molecule Amorphous Drugs with Modulated Differential Scanning Calorimetry and Vacuum Molding Sample Preparation

“…Since thermal conductivity can be an important parameter in pharmaceutical manufacturing but is rather difficult to measure without specific instrumentation, estimates are often used for models describing specific processes. For example, an approximation of 0.18 W/m • C is made in a hot-melt extrusion numerical simulation using a model-based melt viscosity [7]. This study investigated binary amorphous solid dispersions of small molecule organic drugs with vinylpyrrolidone-vinyl acetate copolymer.…”

“…Moreover, thermal conductivity is an important input parameter in many solid-state models, including models for process flow, e.g., in hot melt extrusion [6,7], or models to help understand the material responses to recently developed analytical techniques [8].…”

Boost of solubility and supersaturation of celecoxib via synergistic interactions of methacrylic acid-ethyl acrylate copolymer (1:1) and hydroxypropyl cellulose in ternary amorphous solid dispersions

“…500 mg of every blend was loaded into the VCM device and heated under vacuum for 15 min at a temperature of 160 °C. Annealing temperature was selected based on the CXB melting point of 160.9 °C ( Bochmann et al, 2018 ). The resulting discs were milled utilizing the MM400 ball mill (Retsch GmbH, Haan, Germany) at 30 Hz and passed through a 355 μm sieve to remove larger particle fractions.…”

Assessment of Abrasion-Induced Visual Defects in Twin Screw Wet Granulation Using Wall Friction Measurements

“…The power consumption [A] was recorded during processing of at least several process parameter settings and enabled to calculate granulator torque for these settings. The specific mechanical energy was calculated according to Bochmann et al [ 26 ].…”