Predicting melt rheology for hot-melt extrusion by means of a simple T-measurement

Bochmann, Esther S.; Üstüner, Elgin E.; Gryczke, Andreas; Wagner, Karl G.

doi:10.1016/j.ejpb.2017.05.010

Cited by 27 publications

(22 citation statements)

References 33 publications

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“…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%

“…The parameters n and a of the COP CY-fit and the variables in WLF-fit were considered as constants. The zero-shear viscosity, η 0 , was adjusted via the T g of the investigated blends, using our proposed T g -melt viscosity correlation (Equation (7)),

where a and b are the empirically determined variables [ 20 ]. In the case of a , a temperature-dependency was obtained, but b remained constant over the investigated temperature range.…”

Section: Methodsmentioning

confidence: 99%

“…In our recent work, we proposed a procedure to model the melt viscosity of an ASD by using only its glass transition temperature ( T g ) and the rheological flow profile of the pure polymeric matrix [ 20 ]. It simplifies the application of the HME simulation by reducing the required physicochemical characterization of the ASD.…”

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: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

where a and b are the empirically determined variables [ 20 ]. In the case of a , a temperature-dependency was obtained, but b remained constant over the investigated temperature range.…”

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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“…Softening of the polymer is required to lower the melt viscosity of a formulation as reflected by the influence of barrel temperature and screw speed on the basal torque values: while a direct impact of temperature was observed, a higher screw speed reduced the melt viscosity via shear thinning of the binder (Bochmann et al, 2017;Deshmukh et al, 2016;Villmow et al, 2010). The effect of shear rate on the binders was studied by measuring the complex viscosity ( * ) as function of angular frequency (Fig.…”

Section: Evaluation Of the Tsmg-processmentioning

confidence: 99%

Downstream processing from melt granulation towards tablets: In-depth analysis of a continuous twin-screw melt granulation process using polymeric binders

Grymonpré

Verstraete

Vanhoorne

et al. 2018

European Journal of Pharmaceutics and Biopharmaceutics

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The concept of twin-screw melt granulation (TSMG) has steadily (re)-gained interest in pharmaceutical formulation development as an intermediate step during tablet manufacturing. However, to be considered as a viable processing option for solid oral dosage forms there is a need to understand all critical sources of variability which could affect this granulation technique. The purpose of this study was to provide an in-depth analysis of the continuous TSMG process in order to expose the critical process parameters (CPP) and elucidate the impact of process and formulation parameters on the critical quality attributes (CQA) of granules and tablets during continuous TSMG. A first part of the study dealt with the screening of various amorphous polymers as binder for producing high-dosed melt granules of two model drug (i.e. acetaminophen and hydrochlorothiazide). The second part of this study described a quality-by-design (QbD) approach for melt granulation of hydrochlorothiazide in order to thoroughly evaluate TSMG, milling and tableting stage of the continuous TSMG line. Using amorphous polymeric binders resulted in melt granules with high milling efficiency due to their brittle behaviour without producing excessive amounts of fines, providing high granule yields with low friability. Therefore, it makes them extremely suitable for further downstream processing. One of the most important CPP during TSMG with polymeric binders was the granulation-torque, which - in case of polymers with high T - increased during longer granulation runs to critical levels endangering the continuous process flow. However, by optimizing both screw speed and throughput or changing to polymeric binders with lower T it was possible to significantly reduce this risk. This research paper highlighted that TSMG must be considered as a viable option during formulation development of solid oral dosage forms based on the robustness of the CQA of both melt granules and tablets.

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Analytical Characterisation of 3D‐Printed Medicines

Lima,

Sá‐Barreto,

Cunha‐Filho

2024

3D Printing of Pharmaceutical and Drug Delivery Devices

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Predicting melt rheology for hot-melt extrusion by means of a simple T-measurement

Cited by 27 publications

References 33 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

Downstream processing from melt granulation towards tablets: In-depth analysis of a continuous twin-screw melt granulation process using polymeric binders

Analytical Characterisation of 3D‐Printed Medicines

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