Delta-mannitol to enable continuous twin-screw granulation of a highly dosed, poorly compactable formulation

23 Jul 2024 | Contributor(s): Vanhoorne, V., Almey, R., De Beer, T., Vervaet, C.

In current study, it was investigated if the moisture-mediated polymorphic transition from δ- to β-mannitol during twin screw granulation (TSG) also took place in high drug loaded formulations and if the specific granule morphology associated with the polymorphic transition could enable tableting...

Control oriented modeling of twin-screw granulation in the ConsiGmaTM-25 production plant

09 Jul 2024 | Peer-reviewed journal | Contributor(s): Johannes Khinast, Martin Horn, Jakob Rehrl, Selma Celikovic, Johannes Poms

ConsiGmaTM-25 is a continuous production plant integrating a twin-screw granulation, fluid bed drying, granule conditioning, and a tableting unit. The particle size distribution (PSD), active pharmaceutical ingredient (API) content, and liquid content of wet granules after twin-screw...

Visualization and understanding of the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vercruysse, Jurgen, Toiviainen, Maunu, Fonteyne, Margot, Helkimo, Niko, Ketolainen, Jarkko, Juuti, Mikko, Delaet, Urbain, Van Assche, Ivo, Remon, Jean Paul, Vervaet, Chris, De Beer, Thomas

Over the last decade, there has been increased interest in the application of twin screw granulation as a continuous wet granulation technique for pharmaceutical drug formulations. However, the mixing of granulation liquid and powder material during the short residence time inside the screw...

Use of the channel fill level in defining a design space for twin screw wet granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Gorringe, L. J., Kee, G. S., Saleh, M. F., Fa, N. H., Elkes, R. G.

Twin screw wet granulation is a key process in the continuous manufacture of oral solid dosage forms. Previous Research Article has qualitatively suggested that the channel fill level influences the granules produced. In this paper a quantitative measure of the total volumetric fraction of the...

TPLS as predictive platform for twin-screw wet granulation process and formulation development

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Ryckaert, A., Van Hauwermeiren, D., Dhondt, J., De Man, A., Funke, A., Djuric, D., Vervaet, C., Nopens, I., De Beer, T.

In recent years, the interest in continuous manufacturing techniques, such as twin-screw wet granulation, has increased. However, the understanding of the influence of the combination of raw material properties and process settings upon the granule quality attributes is still limited. In this...

Transfer from High-Shear Batch to Continuous Twin Screw Wet Granulation: A Case Study in Understanding the Relationship Between Process Parameters and Product Quality Attributes

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Beer, Paul, Wilson, David, Huang, Zhenyu, De Matas, Marcel

A twin screw to high-shear batch granulation technology switch was evaluated for a pharmaceutical development project. Differences in granule (particle size distribution and porosity) and tablet (dissolution) quality attributes were analysed for both continuous and batch technologies. Liquid to...

Twin screw granulation - review of current progress

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Thompson, M. R.

Twin screw granulation (TSG) is a new process of interest to the pharmaceutical community that can continuously wet granulate powders, doing so at lower liquid concentrations and with better product consistency than found by a high shear batch mixer. A considerable body of Research Article has...

The Influence of Equipment Design and Process Parameters on Granule Breakage in a Semi-Continuous Fluid Bed Dryer after Continuous Twin-Screw Wet Granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Ryckaert, Alexander, Ghijs, Michael, Portier, Christoph, Djuric, Dejan, Funke, Adrian, Vervaet, Chris, De Beer, Thomas

The drying unit of a continuous from-powder-to-tablet manufacturing line based on twin-screw granulation (TSG) is a crucial intermediate process step to achieve the desired tablet quality. Understanding the size reduction of pharmaceutical granules before, during, and after the fluid bed drying...

The effect of screw configuration and formulation variables on liquid requirements and granule quality in a continuous twin screw wet granulation process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vandevivere, L., Van Wijmeersch, E., Hausler, O., De Beer, T., Vervaet, C., Vanhoorne, V.

The effect of two screw configurations with varying stagger angle was evaluated on the liquid amount required to produce good quality granules for a highly (mannitol-based) and a poorly (DCP-based) soluble formulation containing different binders. It is generally known that the use of a higher...

The impact of channel fill level on internal forces during continuous twin screw wet granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Torrecillas, Carlota Mendez, Gorringe, Lee J., Rajoub, Nazer, Robertson, John, Elkes, Richard G., Lamprou, Dimitrios A., Halbert, Gavin W

The forces experienced by the particles inside a twin screw granulator (TSG) are one of the most difficult parameters to measure quantitatively. However, it is possible to perform accurately this measurement through the use of dye containing calibrated microencapsulated sensors (LAMES) whose...

Switching from batch to continuous granulation: A case study of metoprolol succinate ER tablets

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Kotamarthy, Lalith, Feng, Xin, Alayoubi, Alaadin, Bolla, Pradeep Kumar, Ramachandran, Rohit, Ashraf, Muhammad, O'Connor, Thomas, Zidan, Ahmed

Continuous manufacturing (CM) has been used to produce several immediate release drug products. No extended-release (ER) product manufactured employing CM technology has been approved yet. This study investigated the critical aspects of switching from the batch mode of high shear granulation to...

Simplified formulations with high drug loads for continuous twin-screw granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Meier, R., Thommes, M., Rasenack, N., Krumme, M., Moll, K. -P., Kleinebudde, P.

As different batches of the same excipients will be intermixed during continuous processes, the traceability of batches is complicated. Simplified formulations may help to reduce problems related to batch intermixing and traceability. Twin-screw granulation with subsequent tableting was used to...

Recent progress in continuous and semi-continuous processing of solid oral dosage forms: a review

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Tezyk, Michal, Ernst, Andrzej, Milanowski, Bartlomiej, Lulek, Janina

Continuous processing is an innovative production concept well known and successfully used in other industries for many years. The modern pharmaceutical industry is facing the challenge of transition from a traditional manufacturing approach based on batch-wise production to a continuous...

Recent progress in continuous manufacturing of oral solid dosage forms

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vanhoorne, Valérie, Vervaet, Chris

Continuous drug product manufacturing is slowly being implemented in the pharmaceutical industry. Although the benefits related to the quality and cost of continuous manufacturing are widely recognized, several challenges hampered the widespread introduction of continuous manufacturing of drug...

Qualitative Assessment of a Multi-Scale, Compartmental PBM-DEM Model of a Continuous Twin-Screw Wet Granulation Process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Barrasso, Dana, Ramachandran, Rohit

Wet granulation processes play a crucial role in solid oral dosage manufacturing processes. However, they are often designed empirically with poor efficiency. To implement quality-by-design, a more scientific understanding is desired to predict the effects of process and equipment design and...

Pharmaceutical Applications of Hot-Melt Extrusion: Continuous Manufacturing, Twin-Screw Granulations, and 3D Printing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Maniruzzaman , Mohammed

Recently, hot-melt extrusion (HME) techniques have been presented as innovative platforms to produce various pharmaceuticals. HME is an emerging processing technology used primarily for the manufacture of pharmaceutical solid dispersions. It also combines the advantages of a solvent-free process...

Metamorphosis of Twin Screw Extruder-Based Granulation Technology: Applications Focusing on Its Impact on Conventional Granulation Technology

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Rao, Rajat Radhakrishna, Pandey, Abhijeet, Hegde, Aswathi R., Kulkarni, Vijay Induvadan, Chincholi, Chetan, Rao, Vinay, Bhushan, Indu, Mutalik, Srinivas

In order to be at pace with the market requirements of solid dosage forms and regulatory standards, a transformation towards systematic processing using continuous manufacturing (CM) and automated model-based control is being thought through for its fundamental advantages over conventional batch...

Managing API raw material variability during continuous twin-screw wet granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Stauffer, F, Vanhoorne, VPiker, G, Chavez, PF, Vervaet, C, De;Beer, T

Very few studies have investigated the impact of raw material variability upon the granule critical quality attributes (CQAs) produced via twin-screw wet granulation (i.e., granule size distribution, density, flowability). In this study, the impact of the raw material variability of an active...

Influence of binder attributes on binder effectiveness in a continuous twin screw wet granulation process via wet and dry binder addition

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vandevivere, L., Denduyver, P., Portier, C., Hausler, O., De Beer, T., Vervaet, C., Vanhoorne, V.

The effect of a wide variety of binders on the quality of granules produced via continuous twin screw wet granulation was studied. Anhydrous dicalcium phosphate was used as poorly soluble filler and was granulated applying dry or wet addition of binders. Furthermore, dry and wet binder...

Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Fonteyne, Margot, Wickström, Henrika, Peeters, Elisabeth, Vercruysse, Jurgen, Ehlers, Henrik, Peters, Björn-Hendrik, Remon, Jean Paul, Vervaet, Chris, Ketolainen, Jarkko, Sandler, Niklas, Rantanen, Jukka., Naelapää, Kaisa

Continuous manufacturing gains more and more interest within the pharmaceutical industry. The International Conference of Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product...

Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vanhoorne, V., Bekaert, B., Peeters, E., De Beer, T., Remon, J-P., Vervaet, C.

In most formulations processed via continuous twin screw granulation microcrystalline cellulose (MCC) and/or lactose are used as excipients, but mannitol is also a preferred excipient for wet granulation and tableting due to its non-hygroscopicity and inertness. Therefore, the aim of the current...

Impact of screw configuration on the particle size distribution of granules produced by twin screw granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vercruysse, J, Burggraeve, A., Fonteyne, M., Cappuyns, P., Delaet, U., Van Assche, I., De Beer, T., Remon, J. P., Vervaet, C.

Twin screw granulation (TSG) has been reported by different Research Article groups as an attractive technology for continuous wet granulation. However, in contrast to fluidized bed granulation, granules produced via this technique typically have a wide and multimodal particle size distribution...

Identifying Critical Binder Attributes to Facilitate Binder Selection for Efficient Formulation Development in a Continuous Twin Screw Wet Granulation Process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vandevivere, Lise, Vangampelaere, Maxine, Portier, Christoph, de Backere, Cedrine, Hausler, Olaf, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

The suitability of pharmaceutical binders for continuous twin-screw wet granulation was investigated as the pharmaceutical industry is undergoing a switch from batch to continuous manufacturing. Binder selection for twin-screw wet granulation should rely on a scientific approach to enable...

Granulation of increasingly hydrophobic formulations using a twin screw granulator

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Yu, Shen, Reynolds, Gavin K., Huang, Zhenyu, de Matas, Marcel, Salman, Agba D.

The application of twin screw granulation in the pharmaceutical industry has generated increasing interest due to its suitability for continuous processing. However, an understanding of the impact of formulation properties such as hydrophobicity on intermediate and finished product quality has...

Heat Transfer Evaluation During Twin-Screw Wet Granulation in View of Detailed Process Understanding

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Stauffer, Fanny, Ryckaert, Alexander, Van Hauwermeiren, Daan, Funke, Adrian, Djuric, Dejan, Nopens, Ingmar, De Beer, Thomas

During the last decade, the pharmaceutical industry has shown a growing interest in continuous twin-screw granulation (TSG). Despite flourishing literature on TSG, limited studies focused on fundamental process understanding on its mechanisms. In current study, granule quality attributes along...