Evaluation of torque as an in-process control for granule size during twin-screw wet granulation

Ryckaert, Alexander; Stauffer, F. J.; Funke, Adrian; Djurić, Dejan; Vanhoorne, Valérie; Vervaet, Chris; Beer, Thomas De

doi:10.1016/j.ijpharm.2021.120642

Cited by 13 publications

(9 citation statements)

References 36 publications

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“…As type of feedstock used (X 1 ) was a categorical variable, effect plots were generated to demonstrate the effect of each feedstock on the CQAs of milled extrudates. An effect plot displays a change in response when a factor varies from one level to another with all other factors kept constant at their average values [ 25 ]. The effects of milling speed (X 2 ) and mesh size (X 3 ) were illustrated using response surface plots with regions of maxima and minima [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

Downstream Processing of Itraconazole:HPMCAS Amorphous Solid Dispersion: From Hot-Melt Extrudate to Tablet Using a Quality by Design Approach

Mishra¹,

Richter

Mejía³

et al. 2022

Pharmaceutics

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The downstream processing of hot-melt extruded amorphous solid dispersions (ASDs) into tablets is challenging due to the low tabletability of milled ASDs. Typically, the extrudate strand is sized before milling, as the strand cannot be fed directly into the milling system. At the lab scale, the strand can be sized by hand-cutting before milling. For scaling up, pelletizers or chill roll and flaker systems can be used to break strands. Due to the different techniques used, differences in milling and tablet compaction are to be expected. We present a systematic study of the milling and tableting of an extruded ASD of itraconazole with hypromellose acetate succinate (HPMCAS) as a carrier polymer. The strand was sized using different techniques at the end of the extruder barrel (hand-cutting, pelletizer, or chill roll and flaker) before being milled at varying milling speeds with varying screen sizes. The effects of these variables (sizing technology, milling speed, and screen size) on the critical quality attributes (CQAs) of the milled ASD, such as yield, mean particle size (D50), tablet compaction characteristics, and tablet dissolution, were established using response surface methodology. It was found that the CQAs varied according to sizing technology, with chill roll flakes showing the highest percentage yield, the lowest D50, and the highest tabletability and dissolution rate for itraconazole. Pearson correlation coefficient tests indicated D50 as the most important CQA related to tabletability and dissolution. For certain milling conditions, the milling of hand-cut filaments results in similar particle size distributions (PSDs) to the milling of pellets or chill roll flakes.

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Section: Methodsmentioning

confidence: 99%

Downstream Processing of Itraconazole:HPMCAS Amorphous Solid Dispersion: From Hot-Melt Extrudate to Tablet Using a Quality by Design Approach

Mishra¹,

Richter

Mejía³

et al. 2022

Pharmaceutics

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“…Hence an increase in feed rate has a net positive effect on holdup, and an increase in hold up leads to an increase in the torque of the system. Studies have shown that a large increase in feed rate only increases the Torque by a few percentage points [ 19 , 52 , 53 ], and this has been attributed to an insignificant increase in resistance to the powder flow due to an increase in powder throughput force and a decrease in the occurrence of back mixing. Since feed rate has a direct positive effect on hold up and only has a small indirect positive effect on Torque, the energy per unit gram per unit time decreases with an increase in feed rate.…”

Section: Resultsmentioning

confidence: 99%

Development of a Granule Growth Regime Map for Twin Screw Wet Granulation Process via Data Imputation Techniques

2022

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Twin screw granulation (TSG) is a continuous wet granulation technique that is used widely across different solid manufacturing industries. The TSG has been recognized to have numerous advantages due to its modular design and continuous manufacturing capabilities, including processing a wide range of formulations. However, it is still not widely employed at the commercial scale because of the lack of holistic understanding of the process. This study addresses that problem via. the mechanistic development of a regime map that considers the complex interactions between process, material, and design parameters, which together affect the final granule quality. The advantage of this regime map is that it describes a more widely applicable quantitative technique that can predict the granule growth behavior in a TSG. To develop a robust regime map, a database of various input parameters along with the resultant final granule quality attributes was created using previously published literature experiments. Missing data for several quality attributes was imputed using various data completion techniques while maintaining physical significance. Mechanistically relevant non-dimensional X and Y axis that quantify the physical phenomena occurring during the granulation were developed to improve the applicability and predictability of the regime map. The developed regime map was studied based on process outcomes and granule quality attributes to identify and create regime boundaries for different granule growth regimes. In doing so breakage-dominant growth was incorporated into the regime map, which is very important for TSG. The developed regime map was able to accurately explain the granule growth regimes for more than 90% of the studied experimental points. These experimental were generated at vastly different material, design, and process parameters across various studies in the literature, this further increases the confidence in the developed regime map.

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“…Since torque has been shown to be correlated to granule quality attributes, such as particle size and porosity, 17,18 the goal of this work is to optimize the energy efficiency of the TSG process while maintaining the critical quality attributes of the granules.…”

Section: ■ Introductionmentioning

confidence: 99%

Optimizing Energy Efficiency of a Twin-Screw Granulation Process in Real-Time Using a Long Short-Term Memory (LSTM) Network

Sampat,

Ramachandran

2023

ACS Eng. Au

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Traditional pharmaceutical manufacturing processes for solid oral dosage forms can be inefficient and have been known to produce a large amount of undesired product. With the progressing trend of achieving carbon neutrality, there is an impetus to increase the energy efficiency of these manufacturing processes while maintaining the critical quality attributes of the product. One of the important steps in downstream pharmaceutical manufacturing is wet granulation, and within that, twin screw granulation (TSG) is a popular continuous manufacturing technique. In this study, the energy efficiency of the TSG process was maximized by combining a long-term memory (LSTM) model with an optimization algorithm. The LSTM model was trained on time-series process data obtained from the TSG experimental runs. The optimization process, with the objective of maximizing energy efficiency, was performed using a stochastic optimization algorithm, and constraints were enforced on the process parameter design space. Experimental runs at the optimal process parameters were conducted on the TSG equipment with updates occurring at predefined intervals depending on the optimization scenarios. The purpose of these experimental runs was to validate the capability of increasing the overall process energy efficiency when operating at the optimized process parameters. A maximum increase of 27% was obtained between two tested optimization scenarios while maintaining the yield of the granules at the end of the twin-screw granulation process.

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Evaluation of torque as an in-process control for granule size during twin-screw wet granulation

Cited by 13 publications

References 36 publications

Downstream Processing of Itraconazole:HPMCAS Amorphous Solid Dispersion: From Hot-Melt Extrudate to Tablet Using a Quality by Design Approach

Downstream Processing of Itraconazole:HPMCAS Amorphous Solid Dispersion: From Hot-Melt Extrudate to Tablet Using a Quality by Design Approach

Development of a Granule Growth Regime Map for Twin Screw Wet Granulation Process via Data Imputation Techniques

Optimizing Energy Efficiency of a Twin-Screw Granulation Process in Real-Time Using a Long Short-Term Memory (LSTM) Network

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