The Use of a Closed Feed Frame for the Development of Near-Infrared Spectroscopic Calibration Model to Determine Drug Concentration

23 Jul 2024 | Contributor(s): Movilla-Meza, Nathaly A., Sierra-Vega, Nobel O., Alvarado-Hernández, Bárbara B., Méndez, Rafael, Romañach, Rodolfo J.

Purpose: This study evaluates the use of the closed feed frame as a material sparing approach to develop near-infrared (NIR) spectroscopic calibration models for monitoring blend uniformity. The effect of shear induced by recirculation on NIR spectra was also studied. Methods: Calibration models...

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...

Cleaning of direct compression continuous manufacturing equipment through displacement of API residues by excipients

23 Jul 2024 | Contributor(s): Patel, Dhavalkumar S, Méndez, Rafael, Romañach, Rodolfo J

This feasibility study evaluates a cleaning process designed to avoid the use of detergents and reduce operator exposure to the active pharmaceutical ingredient (API). The continuous manufacturing equipment was cleaned using excipients to displace ibuprofen residues from the system. The cleaning...

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 Use of Near-Infrared and Microwave Resonance Sensing to Monitor a Continuous Roller Compaction Process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Austin, John, Gupta, Anshu, Mcdonnell, Ryan, Reklaitis, Gintaras V., Harris, Michael T

Roller compaction is commonly used in the pharmaceutical and nutraceutical industries to increase and narrow the size distribution of a particulate material, making it easier to process. Both the moisture content of the material and the density of the roller compacted ribbon affect the uniformity...

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...

Supervisory Control System for Monitoring a Pharmaceutical Hot Melt Extrusion Process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Markl, Daniel, Wahl, Patrick R, Menezes, José C, Koller, Daniel M, Kavsek, Barbara, Francois, Kjell, Roblegg, Evaa, Khinast, Johannes G.

Continuous pharmaceutical manufacturing processes are of increased industrial interest and require uni- and multivariate Process Analytical Technology (PAT) data from different unit operations to be aligned and explored within the Quality by Design (QbD) context. Real-time pharmaceutical process...

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...

Robustness of a continuous direct compression line against disturbances in feeding

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Karttunen A.-P., Poms J., Sacher S., Sparén A., Ruiz Samblás C., Fransson M., Martin De Juan L., Remmelgas J., Wikström H., Hsiao W.-K., Folestad S., Korhonen O.

The aim of the current study was to characterize the robustness of an integrated continuous direct compression (CDC) line against disturbances from feeding, i.e. impulses of API and short step disturbances. These disturbances mimicked typical variations that can be encountered during long-term...

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...

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...

Real-time monitoring of drug concentration in a continuous powder mixing process using NIR spectroscopy

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vanarase, Aditya, Alcalà, Manel, Jerez-Rozo, Jackeline, Muzzio, Fernando, Romañach, Rodolfo

A non-destructive NIR spectroscopic method was used to acquire on-line spectra of a continuous mixing process, and evaluate the performance of this novel system. Partial least squares (PLS) calibration models were developed and used for real-time determination of active ingredient concentration...

Real-time process monitoring in a semi-continuous fluid-bed dryer - microwave resonance technology versus near-infrared spectroscopy

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Peters, Johanna, Teske, Andreas, Taute, Wolfgang, Döscher, Claas, Höft, Michael, Knöchel, Reinhard, Breitkreutz, Jörg

The trend towards continuous manufacturing in the pharmaceutical industry is associated with an increasing demand for advanced control strategies. It is a mandatory requirement to obtain reliable real-time information on critical quality attributes (CQA) during every process step as the decision...

Real-Time Quantification of Low-Dose Cohesive Formulations within a Sampling Interface for Flowing Powders

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sierra-Vega, Nobel. O., Romañach, Rodolfo J., Mendez, Rafael

This study investigates the performance of a sampling interface for monitoring cohesive, flowing powder formulations with Hausner's Ratio and Carr's Index higher than 1.5 and 35%, respectively. The sampler device was operated in combination with near-infrared (NIR) spectroscopy to quantify...

Real-time monitoring of particle size distribution in a continuous granulation and drying process by near infrared spectroscopy

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Pauli, V, Roggo, YKleinebudde, P, Krumme, M

In continuous granulation, it can be important to control granules particle size distribution (PSD), as it may affect final product quality. Near infrared spectroscopy (NIRS) is already a routine analytical procedure within pharmaceutical continuous manufacturing for the in-line analysis of...

Quality-by-Design III: Application of Near-Infrared Spectroscopy to Monitor Roller Compaction In-process and Product Quality Attributes of Immediate Release Tablets

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Kona, Ravikanth, Fahmy, Raafat M., Claycamp, Gregg, Polli, James E., Martinez, Marilyn, Hoag, Stephen W.

The objective of this study is to use near-infrared spectroscopy (NIRS) coupled with multivariate chemometric models to monitor granule and tablet quality attributes in the formulation development and manufacturing of ciprofloxacin hydrochloride (CIP) immediate release tablets. Critical roller...

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...