Critical review on the role of excipient properties in pharmaceutical powder-to-tablet continuous manufacturing

13 Aug 2024 | Peer-reviewed journal | Contributor(s): Sara Fathollahi, Pauline H. M. Janssen, Bastiaan H. J. Dickhoff, Henderik W. Frijlink

The pharmaceutical industry is gradually changing batch-wise manufacturing processes to continuous manufacturing processes, due to the advantages it has to offer. The final product quality and process efficiency of continuous manufacturing processes is among others impacted by the properties of...

Process intensification of pharmaceutical powder blending at commercial throughputs by utilizing semi-continuous mini-blending

13 Aug 2024 | Peer-reviewed journal | Contributor(s): Maarten Jaspers, Florian Tegel, Timo P. Roelofs, Fabian Starsich, Yunfei Li Song, Bernhard Meir, Richard Elkes, Bastiaan H.J. Dickhoff

Process intensification involves the miniaturization of equipment while retaining process throughput and performance. The pharmaceutical industry can benefit from this approach especially during drug product development, where the availability of active pharmaceutical ingredients (API) is often...

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

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

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

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

Using Residence Time Distributions (RTDs) to Address the Traceability of Raw Materials in Continuous Pharmaceutical Manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Engisch, William, Muzzio, Fernando

Continuous processing in pharmaceutical manufacturing is a relatively new approach that has generated significant attention. While it has been used for decades in other industries, showing significant advantages, the pharmaceutical industry has been slow in its adoption of continuous processing,...

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Baumann, M, Baxendale, IR

The implementation of continuous flow processing as a key enabling technology has transformed the way we conduct chemistry and has expanded our synthetic capabilities. As a result many new preparative routes have been designed towards commercially relevant drug compounds achieving more efficient...

The Use of PAT and Off-line Methods for Monitoring of Roller Compacted Ribbon and Granule Properties with a View to Continuous Processing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): McAuliffe M.A.P., Omahony G.E., Blackshields C.A., Collins J.A., Egan D.P., Kiernan L., Oneill E., Lenihan S., Walker G.M., Crean A.M.

Real-time process monitoring using process analytical technology (PAT) tools can augment process understanding, enable improved process control, and hence facilitate the production of high-quality pharmaceutical products. While beneficial for batch processes, the availability of PAT tools to...

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...

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...

Small-Volume Continuous Manufacturing of Merestinib. Part 1. Process Development and Demonstration

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Cole, KP, Reizman, BJHess, M, Groh, JM, Laurila, ME, Cope, RF, Campbell, BM, Forst, MB, Burt, JL, Maloney, TD, Johnson, MD, Mitchell, D, Polster, CS, Mitra, AW, Boukerche, M, Conder, EW, Braden, TM, Miller, RD, Heller, MR, Phillips, JL, Howell, JR

Development of a small volume continuous process that used a combination of batch and flow unit operations to manufacture the small molecule oncolytic candidate merestinib is described. Continuous processing was enabled following the identification and development of suitable chemical...

Small-Volume Continuous Manufacturing of Merestinib. Part 2.Technology Transfer and cGMP Manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Reizman, Brandon J., Hess, Molly, Burt, Justin L., Maloney, Todd D., Johnson, Martin D., Laurila, Michael E., Cope, Richard F., Luciani, Carla V., Buser, Jonas Y., Campbell, Bradley M., Forst, Mindy B., Mitchell, David, Braden, Timothy M., Lippelt, Christopher K., Boukerche, Moussa, Starkey, Derek R., Miller, Richard D., Chen, Jing, Sun, Baoquan, Kwok, Martin, Zhang, Xin, Tadayon, Sam, Huang, Ping

Technology transfer of a small volume continuous (SVC) process and Current Good Manufacturing Practices (cGMP) manufacturing of merestinib are described. A hybrid batch-SVC campaign was completed at a contract manufacturing organization under cGMP. The decision process by which unit operations...

Simulation-Based Design of an Efficient Control System for the Continuous Purification and Processing of Active Pharmaceutical Ingredients

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sen, M, Singh, R, Ramachandran, R

In this study, an efficient system-wide controlsystem has been designed for the integrated continuous purification and processing of the active pharmaceutical ingredient (API). The control strategy is based on the regulatory PID controller which is most widely used in the manufacturing industry...

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...

Real-Time Monitoring of Powder Mass Flowrates for Plant-Wide Control of a Continuous Direct Compaction Tablet Manufacturing Process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Huang, Yan-Shu, Medina-González, Sergio Straiton, Benjamin Keller, Joshua, Marashdeh, Qussai, Gonzalez, Marcial, Nagy, Zoltan, Reklaitis, Gintaras V.

While measurement and monitoring of powder/particulate mass flow rate are not essential to the execution of traditional batch pharmaceutical tablet manufacturing, in continuous operation, it is an important additional critical process parameter. It has a key role both in establishing that the...

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...

Process optimization for continuous extrusion wet granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Tan, L, Carella, AJ, Ren, YK, Lo, JB

Three granulating binders in high drug-load acetaminophen blends were evaluated using high shear granulation and extrusion granulation. A polymethacrylate binder enhanced tablet tensile strength with rapid disintegration in simulated gastric fluid, whereas polyvinylpyrrolidone and hydroxypropyl...

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...

Process dynamics and control of API manufacturing and purification processes

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sen, Maitraye, Singh, Ravendra, Ramachandran, Rohit

The pharmaceutical industries have started transitioning toward continuous mode of manufacturing recently. Due to many advantages of the continuous manufacturing over the traditional alternatives, the industries are putting huge effort to efficiently adapt the continuous processing mode. However,...

Process design applied to optimise a directly compressible powder produced via a continuous manufacturing process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Gonnissen, Y., Goncalves, S. I. V., De Geest, B. G., Remon, J. P., Vervaet, C.

Manufacturing of 'ready-to-compress' powder mixtures for direct compression was performed by spray drying, without granulation, milling and/or blending steps in between spray drying and compaction. Powder mixtures containing acetaminophen, mannitol, erythritol, maltodextrin, crospovidone,...

Process analytical technology for continuous manufacturing tableting processing: A case study

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Pauli, Victoria, Pellegatti, Laurent, Nguyen Trung, Nhat Quang, Elbaz, Frantz, Ensslin, Simon, Kleinebudde, Peter, Roggo, Yves, Krumme, Markus

The use of Near Infrared Spectroscopy (NIRS) as a fast and non-destructive technique was employed for the control and monitoring of the tableting step during a continuous manufacturing process. Two NIRS methods were optimized in order to in-line control the blend uniformity in the tablet feed...

Process analytical technology in continuous manufacturing of a commercial pharmaceutical product

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vargas, Jenny, Nielsen, Sarah, Cárdenas, Vanessa, Gonzalez, Anthony, Aymat, Efrain, Almodovar, Elvin, Classe, Gustavo, Colón, Yleana, Sanchez, Eric, Romañach, Rodolfo

The implementation of process analytical technology and continuous manufacturing at an FDA approved commercial manufacturing site is described. In this direct compaction process the blends produced were monitored with a Near Infrared (NIR) spectroscopic calibration model developed with partial...

Pharmaceutical Crystallization

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Chen, J, Sarma, BEvans, JMB, Myerson, AS

Crystallization is crucial in the pharmaceutical industry as a separation process for intermediates and as the final step in the manufacture of active pharmaceutical ingredients (APIs). In this perspective article to celebrate 10 years of Crystal Growth & Design, we focus on three areas related...