A comprehensive analysis and optimization of continuous twin-screw granulation processes via sequential experimentation strategy

09 Jun 2023 | Contributor(s): Meng, Wei, Rao, Kallakuri Suparna, Snee, Ronald D., Ramachandran, Rohit., Muzzio, Fernando J

Nowadays twin-screw granulation has been emerging as an attractive continuous wet granulation technique. This study was geared towards better process design and understanding with emphasis on bridging the knowledge gap between input and output variables by employing sequential experimentation...

Advances in Twin-Screw Granulation Processing

09 Jun 2023 | Contributor(s): Nandi, Uttom, Trivedi, Vivek, Ross, Steven A., Douroumis, Dennis

Twin-screw granulation (TSG) is a pharmaceutical process that has gained increased interest from the pharmaceutical industry for its potential for the development of oral dosage forms. The technology has evolved rapidly due to the flexibility of the equipment design, the selection of the process...

Application of continuous twin screw granulation for the metformin hydrochloride extended release formulation

09 Jun 2023 | Contributor(s): Kim, Su-Hyeon, Hwang, Kyu-Min, Cho, Cheol-Hee, Nguyen, Thi-Tram, Seok, Su Hyun, Hwang, Kyu-Mok, Kim, Ju-Young, Park, Chun-Woong, Rhee, Yun-Seok, Park, Eun-Seok

This study focuses on evaluating the potential of transferring from a batch process to continuous process for manufacturing of the extended release formulation. Metformin hydrochloride (HCl) was used in the model formulation which was intended to contain the high amount of hydrophilic drug. The...

Asymmetric distribution in twin screw granulation

09 Jun 2023 | Contributor(s): Seem, Tim Chan, Rowson, Neil A., Gabbott, Ian, de Matas, Marcel, Reynolds, Gavin K., Ingram, Andy

Positron Emission Particle Tracking (PEPT) was successfully employed to validate measured transverse asymmetry in material distribution in the conveying zones of a Twin Screw Granulator (TSG). Flow asymmetry was established to be a property of the granulator geometry and dependent on fill level....

Breakage and drying behaviour of granules in a continuous fluid bed dryer: Influence of process parameters and wet granule transfer

09 Jun 2023 | Contributor(s): De Leersnyder, F., Vanhoorne, V., Bekaert, H., Vercruysse, J., Ghijs, M., Bostijn, N., Verstraeten, M., Cappuyns, P., Van Assche, I., Vander Heyden, Y., Ziemons, E., Remon, J. P., Nopens, I., Vervaet, C., De Beer, T.

Although twin screw granulation has already been widely studied in recent years, only few studies addressed the subsequent continuous drying which is required after wet granulation and still suffers from a lack of detailed understanding. The latter is important for optimisation and control and,...

Characteristics of multi-component formulation granules formed using distributive mixing elements in twin screw granulation

09 Jun 2023 | Contributor(s): Pradhan, Shankali U., Sen, Maitraye, Li, Jiayu, Gabbott, Ian, Reynolds, Gavin, Litster, James D., Wassgren, Carl R.

This work examines the influence of pharmaceutical powder formulation characteristics on granule properties formed using distributive mixing elements (DMEs) in twin screw granulation. High and low drug dose formulations with three different active pharmaceutical ingredients (APIs) were...

Continuous Melt Granulation for Taste-Masking of Ibuprofen

09 Jun 2023 | Contributor(s): Forster, Seth P., Lebo, David B.

This book covers key aspects of the continuous manufacturing of pharmaceuticals. The first part provides an overview of key chemical engineering principles and the current regulatory environment. The second covers existing technologies for manufacturing both small-molecule-based products and...

Continuous twin screw granulation and fluid bed drying: A mechanistic scaling approach focusing optimal tablet properties

09 Jun 2023 | Contributor(s): Menth, Judith, Maus, Martin, Wagner, Karl G.

This study provides the results of investigation on scaling approaches for three differently-sized continuous granulation lines, each consisting of a twin screw wet granulation process and a continuous fluid bed drying process. To check the initial scaling approach with regard to granule and...

Continuous twin screw granulation: A complex interplay between formulation properties, process settings and screw design

09 Jun 2023 | Contributor(s): Portier, Christoph, Pandelaere, KDelaet, U, Vigh, T, Di, Pretoro, G, De, Beer, T, Vervaet, C, Vanhoorne, V

Due to the numerous advantages over batch manufacturing, continuous manufacturing techniques such as twin screw wet granulation are rapidly gaining importance in pharmaceutical production. Since a large knowledge gap on the importance of formulation variables exists, this study systematically...

Continuous Twin Screw Granulation: A Review of Recent Progress and Opportunities in Formulation and Equipment Design

09 Jun 2023 | Contributor(s): Portier, Christoph, Vervaet, Chris, Vanhoorne, Valérie

Continuous twin screw wet granulation is one of the key continuous manufacturing technologies that have gained significant interest in the pharmaceutical industry as well as in academia over the last ten years. Given its considerable advantages compared to wet granulation techniques operated in...

Continuous twin screw granulation: Impact of binder addition method and surfactants on granulation of a high-dosed, poorly soluble API

09 Jun 2023 | Contributor(s): Portier, Christoph, Vigh, Tamas, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

Despite the recent commercialization of several drug products manufactured through continuous manufacturing techniques, knowledge on the formulation aspect of these techniques, such as twin screw wet granulation, is still rather limited. Previous Research Article identified lactose/MCC/HPMC as a...

Continuous twin screw granulation: Impact of microcrystalline cellulose batch-to-batch variability during granulation and drying - A QbD approach

09 Jun 2023 | Contributor(s): Portier, Christoph, Vigh, Tamas, Di Pretoro, Giustino, Leys, Jan, Klingeleers, Didier, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

Despite significant advances in the Research Article domain of continuous twin screw granulation, limited information is currently available on the impact of raw material properties, especially considering batch-to-batch variability. The importance of raw material variability and subsequent...

Continuous twin screw granulation: Influence of process and formulation variables on granule quality attributes of model formulations

09 Jun 2023 | Contributor(s): Portier, Christoph, Pandelaere, Kenny, Delaet, Urbain, Vigh, Tamas, Kumar, Ashish, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

In recent years, continuous manufacturing techniques, such as twin screw wet granulation, have gained significant momentum. Due to the large diversity of the (model) formulations and equipment, it is often difficult to generalize conclusions about the importance of process settings. As only...

Continuous twin screw granulation: Influence of process variables on granule and tablet quality

09 Jun 2023 | Contributor(s): Vercruysse, J., Diaz, D. Cordoba, Peeters, E., Fonteyne, M., Delaet, U., Van Assche, I., De Beer, T., Remon, J. P., Veryaet, C.

The aim of the current study was to screen theophylline (125 mg) tablets manufactured via twin screw granulation in order to improve process understanding and knowledge of process variables that determine granule and tablet quality. A premix of theophylline anhydrate, alpha-lactose monohydrate...

Continuous twin screw granulation: Robustness of lactose/MCC-based formulations

09 Jun 2023 | Contributor(s): Portier, Christoph, De Vriendt, Charlotte, Vigh, Tamas, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

In recent years, significant progress has been made in the field of continuous twin screw granulation. However, only limited knowledge is currently available on the impact of active pharmaceutical ingredient (API) properties on granule quality and processability. In this study, the response...

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...

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

23 Jul 2024 | Peer-reviewed journal | 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...

Development of an in-line Raman spectroscopic method for continuous API quantification during twin-screw wet granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Harting Julia, Kleinebudde, Peter

Raman spectroscopy was evaluated as a process analytical technology (PAT) tool for continuous API quantification during twin-screw wet granulation. Therefore, a Raman probe was implemented in front of the granulator barrel. This setup enabled the collection of Raman spectra upon a constant...

Effect of formulation and process variables on lipid based sustained release tablets via continuous twin screw granulation: A comparative study

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Kallakunta, Venkata Raman, Tiwari, Roshan, Sarabu, Sandeep, Bandari, Suresh, Repka, Michael A.

The current study's aim is to prepare lipid based sustained release tablets via a twin-screw granulation technique and compare those dosage forms with conventional techniques, namely wet granulation and direct compression. The granules were successfully manufactured in a single-step, continuous...

Examining drug hydrophobicity in continuous wet granulation within a twin screw extruder

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Li, H., Thompson, M. R., O'Donnell, K. P.

The influence of active pharmaceutical ingredient (API) hydrophobicity on continuous wet granulation was studied in twin screw granulation utilizing foamed binder delivery. The APIs examined were caffeine, acetaminophen, ibuprofen and griseofulvin and the drug load was maintained constant at 15...

Exploratory studies in heat-assisted continuous twin-screw dry granulation: A novel alternative technique to conventional dry granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Kallakunta, Venkata Raman, Patil, Hemlata, Tiwari, Roshan, Ye, Xingyou, Upadhye, Sampada, Vladyka, Ronald S., Sarabu, Sandeep, Kim, Dong Wuk, Bandari, Suresh, Repka, Michael A.

Dry granulation is the preferred technique for solvent-sensitive products, especially drugs with stability problems such as hydrolysis. Twin-screw granulation is a continuous granulation technique, offering a potential alternative to conventional dry granulation techniques such as roller...

From powder to tablets: Investigation of residence time distributions in a continuous manufacturing process train as basis for continuous process verification

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Pauli, Victoria, Kleinebudde, Peter, Krumme, Markus

The essence of Continuous Manufacturing (CM) resides in the fact that continuous process units are directly connected to each other forming a continuous process train. The thorough understanding of material flow in this train based on suitable sensors, including on-line process analytical...

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...

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...