Numerical simulation of hot-melt extrusion processes for amorphous solid dispersions using model-based melt viscosity

Bochmann, Esther S.; Steffens, Kristina E.; Gryczke, Andreas; Wagner, Karl G.

doi:10.1016/j.ejpb.2017.12.001

Cited by 26 publications

(22 citation statements)

References 37 publications

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“…To investigate the influence of API and its weight fraction on the physical properties of the respective API/COP blend, the true density ( ρ ) and specific heat capacity ( c p ) of the physical mixtures and extrudates were measured, listed in Table 2 . In the case of pure COP, the true density increased slightly from powder (1178 kg/m 3 ) to the extruded material (1.191 kg/m 3 ) [ 21 ]. In comparison to the physical mixtures of the COP-blends, the true density was similar to pure COP with a negligible increase of up to 4% ( ρ ≤ 1230 kg/m 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…All of the investigated APIs belong to BCS (Biopharmaceutics classification system) Class II and were thermally stable over the applied temperature range. None of the selected APIs were used to establish the T g -melt viscosity correlation in the first place, and thus served for model validation [ 20 , 21 ].…”

Section: Methodsmentioning

confidence: 99%

“…In our recent work, we proposed a correlation between T g and zero-shear viscosity η 0 of an amorphous solid dispersion and its use in HME simulation [ 20 , 21 ]. At a set reference temperature, the rheological flow profile of pure COP with its variables in the CY-fit and WLF-fit served as a starting point for the model-based viscosity calculation.…”

Section: Methodsmentioning

confidence: 99%

“…In the case of conventional simulation, the physical properties and melt viscosity of the desired API/COP-blend were used. In the adopted simulation, the physical properties of the pure COP and model-based melt viscosity were employed instead [ 21 ]. Both of the simulation assumptions use the identical simulation algorithm, but the product related input parameter for simulation varies, leading to a reduced experimental effort in the case of the adopted simulation.…”

Section: Methodsmentioning

confidence: 99%

“…It simplifies the application of the HME simulation by reducing the required physicochemical characterization of the ASD. Therefore, the experimental effort was decreased without compromising the accuracy of the computation, which has been proven by comparing the simulation using model-based melt viscosity, conventional simulation, and the data of experimental trials [ 21 ]. However, all of the investigated APIs so far were already used to establish the T g -melt viscosity correlation in the first place, and thus a validation with new APIs is needed.…”

Section: Introductionmentioning

confidence: 99%

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

2018

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2018

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Insights into influence mechanism of polymeric excipients on dissolution of drug formulations: A molecular interaction‐based theoretical model analysis and prediction

Hao

Luebbert

et al. 2021

AIChE Journal

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This study provides an analysis of the dissolution mechanism of poorly water‐soluble drugs, indomethacin (IND) and naproxen (NAP), from polyvinyl acetate (PVAc) and polyvinylpyrrolidone/vinyl acetate 64 (PVPVA 64) formulations under the combination of the Perturbed‐Chain Statistical Associating Fluid Theory (PC‐SAFT) and a chemical‐potential‐gradient model. Moreover, the dissolution kinetics of both drugs from these polymeric formulations were modeled in conformity with the in vitro experimental data obtained by means of a rotating disk system (USP II). The combination of the thermodynamic model PC‐SAFT and a chemical‐potential‐gradient model was demonstrated to be an efficient approach to explain the drug dissolution mechanism from the drug/PVAc and PVPVA 64 formulations. These results have implications in reducing experimental time and resources for the sustained dissolution kinetics profile determination without compromising accuracy, in particular for the system of the drug/PVAc formulation when obtaining continuous drug dissolution in this work.

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Crystallization of Amorphous Pharmaceuticals at Ambient and Elevated Pressure Conditions

Knapik-Kowalczuk

Chmiel

Paluch

2020

Crystallization as Studied by Broadband Dielectric Spectroscopy

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Numerical simulation of hot-melt extrusion processes for amorphous solid dispersions using model-based melt viscosity

Cited by 26 publications

References 37 publications

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

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

Insights into influence mechanism of polymeric excipients on dissolution of drug formulations: A molecular interaction‐based theoretical model analysis and prediction

Crystallization of Amorphous Pharmaceuticals at Ambient and Elevated Pressure Conditions

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