Application of FT-NIR Analysis for In-line and Real-Time Monitoring of Pharmaceutical Hot Melt Extrusion: a Technical Note

09 Jun 2023 | Contributor(s): Vo, Anh Q., He, Herman, Zhang, Jiaxiang, Martin, Scott, Chen, Rui, Repka, Michael A.

Continuous manufacturing, a gaining interest paradigm in the pharmaceutical industry, requires in-process monitoring of critical process parameters to ensure product consistency. This study demonstrated the application of Fourier transform near-infrared (FT-NIR) spectroscopy in conjunction with...

Automated and continuous synthesis of drug substances

24 Apr 2024 | Peer-reviewed journal | Contributor(s): Sacher, Stephan, Castillo, Ismael, Rehrl, Jakob, Sagmeister, Peter, Lebl, René, Kruisz, Julia, Celikovic, Selma, Sipek, Martin, Williams, Jason D., Kirschneck, Dirk, Kappe, C. Oliver, Horn, Martin

A continuous synthesis line was developed integrating different common reaction steps namely nitration, substitution and hydrogenation. Mesalazine as model drug substance was produced from 2-chlorobenzoic acid in continuous flow mode. A multi-instrument PAT strategy was implemented to equip the...

Comparison Between Pure Component Modeling Approaches for Monitoring Pharmaceutical Powder Blends with Near‑Infrared Spectroscopy in Continuous Manufacturing Schemes

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Rish, Adam J., Henson, Samuel R., Alam, Md. Anik, Liu, Yang, Drennen, James K., Anderson, Carl A.

Near-infrared (NIR) spectroscopy has become an important process analytical technology (PAT) for monitoring and implementing control in continuous manufacturing (CM) schemes. However, NIR requires complex multivariate models to properly extract the relevant information and the traditional model...

Continuous Crystallization Processes in Pharmaceutical Manufacturing: A Review

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Orehek, J, Teslic, D, Likozar, B

This scientific paper presents an overview of continuous solution crystallization in the pharmaceutical industry. Since the specific knowledge spectrum of precipitation is very broad, topics covering the following were analyzed and assessed in detail: a comparison between batch and continuous...

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...

Development of a methodology to estimate error in the on-line measurements of blend uniformity in a continuous powder mixing process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vanarase, Aditya, Järvinen, Maiju, Paaso, Janne, Muzzio, Fernando

In this paper, a multi-point fiber optic based NIR system was implemented to monitor API concentration at the discharge of a continuous mixer. The sample size being interrogated by NIR was determined by measuring the velocity of the powder on the chute, which allowed selection of the number of...

Evaluation of an in-line NIR spectroscopic method for the determination of the residence time in a tablet press

09 Jun 2023 | Peer-reviewed journal | Contributor(s): De Leersnyder, Fien, Vanhoorne, Valérie, Kumar, Ashish, Vervaet, Chris, De Beer, Thomas

In the current study, the ability to use in-line NIR inside the feed frame of a tablet press to monitor the residence time distribution inside the tablet press was investigated. Pulse-response experiments were performed. In-line measurements inside the feed frame were compared to measurements on...

Feed frame: The last processing step before the tablet compaction in pharmaceutical manufacturing

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

The feed frame is a force-feeding device used in the die filling process. The die filling process is crucial within pharmaceutical manufacturing to guarantee the critical quality attributes of the tablets. In recent years, interest in this unit has increased because it can affect the properties...

Hot melt extrusion technology for continuous manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Furqan Tahir, Lovett. David

Hot melt extrusion (HME), a manufacturing technique traditionally used in the plastic and food industries, is now attracting significant interest from the pharmaceutical manufacturing sector. This is primarily because HME enables the continuous manufacture of a wide variety of dosage...

How to measure coating thickness of tablets: Method comparison of optical coherence tomography, near-infrared spectroscopy and weight-, height- and diameter gain

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Wahl, P. R., Peter, A., Wolfgang, M., Khinast, J. G.

Film coating of pharmaceutical dosage forms, such as tablets and pellets, can be used to tailor the drug release profile. With that regard, a uniform coating thickness of a single tablet (intra-tablet), all tablets (inter-tablet) and subsequent batches (inter-batch) is crucial. We present a...

In-line particle size measurement based on image analysis in a fully continuous granule manufacturing line for rapid process understanding and development

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Madarász, Lajos, Köte, Ákos, Hambalkó, Bence, Csorba, Kristóf, Kovács, Viktor, Lengyel, László, Marosi, Györgya, Farkas, Attilaa, Nagy, Zsombor Kristóf, Domokos, András

The present paper serves as a demonstration how an in-line PAT tool can be used for rapid and efficient process development in a fully continuous powder to granule line consisting of an interconnected twin-screw wet granulator, vibrational fluid bed dryer, and a regranulating mill. A new method...

In-line Raman spectroscopic monitoring and feedback control of a continuous twin-screw pharmaceutical powder blending and tableting process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Nagy, Brigitta, Farkas, Attila, Gyurkes, Martin, Komaromy-Hiller, Szofia, Demuth, Balazs, Szabo, Bence, Nusser, David, Borbas, Eniko, Marosi, Gyorgy, Nagy, Zsombor Kristof

The integration of Process Analytical Technology (PAT) initiative into the continuous production of pharmaceuticals is indispensable for reliable production. The present paper reports the implementation of in-line Raman spectroscopy in a continuous blending and tableting process of a...

In-line UV-Vis Spectroscopy as a Fast-Working Process Analytical Technology (PAT) during Early Phase Product Development Using Hot Melt Extrusion (HME)

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Schlindwein, Walkiria, Bezerra, Mariana, Almeida, Juan, Berghaus, Andreas, Owen, Martin, Muirhead, Gordon

This paper displays the potential of an in-line PAT system for early phase product development during pharmaceutical continuous manufacturing following a Quality by Design (QbD) framework. Hot melt extrusion (HME) is used as continuous manufacturing process and UV–Vis spectroscopy as an in-line...

Inline monitoring and a PAT strategy for pharmaceutical hot-melt extrusion

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Wahl, PR, Treffer, DMohr, S, Roblegg, E, Koscher, G, Khinast, JG

Implementation of continuous manufacturing in the pharmaceutical industry requires tight process control. This study focuses on a PAT strategy for hot melt extrusion of vegetable calcium stearate (CaSt) as matrix carrier and paracetamol as active pharmaceutical ingredient (API). The extrusion was...

Method transfer of a near-infrared spectroscopic method for blend uniformity in a poorly flowing and hygroscopic blend

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Alvarado-Hernández, Bárbara, Scicolone, James, Ortega-Zuñiga, Carlos, Román-Ospino, Andrés, Colón-Lugo, Yleana, Aymat, Efrain, Sánchez, Eric, Muzzio, Fernando, Romañach, Rodolfo

The challenges in transferring and executing a near-infrared (NIR) spectroscopic method for croscarmellose (disintegrant) in binary blends for a continuous manufacturing (CM) process are presented. This work demonstrates the development of a NIR calibration model and its use to determine the...

Near infrared spectroscopic calibration models for real time monitoring of powder density

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Román-Ospino, Andrés, Singh, Ravendra, Ierapetritoua, Marianthi, Ramachandrana, Rohit, Mendez, Rafael, Ortega-Zuñiga, Carlos, Muzzio, Fernando, Romañach, Rodolfo

Near infrared spectroscopic (NIRS) calibration models for real time prediction of powder density (tap, bulk and consolidated) were developed for a pharmaceutical formulation. Powder density is a critical property in the manufacturing of solid oral dosages, related to critical quality attributes...

Near-infrared spectroscopic applications in pharmaceutical particle technology

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Razuc, M, Grafia, AGallo, L, Ramirez-Rigo, MV, Romanach, RJ

Near-infrared spectroscopy (NIRS) is nowadays an established analytical technique in the pharmaceutical industry. The aim of this review is to present the progress of NIRS in providing useful information for pharmaceutical particle technology. NIR methods are now developed to characterize a wide...

PAT for pharmaceutical manufacturing process involving solid dosages forms

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Román-Ospino, Andrés D, Cárdenas, Vanessa Ortega-Zuñiga, Carlos, Singh, Ravendra

This chapter summarizes important considerations to develop multivariate methods for pharmaceuticals process monitoring and quality control in solid dosages forms based on spectroscopic techniques. The stages described in each section aimed to explain relevant knowledge of the calibration...

PAT Implementation on a Mobile Continuous Pharmaceutical Manufacturing System: Real-Time Process Monitoring with In-Line FTIR and Raman Spectroscopy

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Miyai, Yuma, Formosa, Anna, Armstrong, Cameron, Marquardt, Brian, Rogers, Luke, Roper, Thomas

The strategies and experimental methods for implementation of process analytical technology (PAT) on the mobile pharmaceutical manufacturing system, Pharmacy on Demand (PoD), are discussed. With multiple processes to be monitored on the PoD end-to-end continuous manufacturing process, PAT and its...

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...

Raman Spectroscopy for Monitoring the Continuous Crystallization of Carbamazepine

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Acevedo, D, Mohammad, Adil, Pavurala, Naresh, Wu, Wei-Lee, O'Connor, Thomas F., Nagy, Zoltan K, Yang, Xiaochuan, Cruz, CN

Crystallization has a significant impact on the properties of the active pharmaceutical ingredient (API) since it is the final step in the manufacturing of the drug substance and determines particle size distribution, purity, shape, and polymorphs. Many publications have focused on the...

Real-time feedback control of twin-screw wet granulation based on image analysis

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Madarasz, Lajos, Hoffer, Istvan, Szabo, Barnabas, Csontos, Istvan, Pataki, Hajnalka, Demuth, Balazs, Szabo, Bence, Csorba, Kristof, Nagy, Zsombor Kristof, Marosi, Gyorgy

The present paper reports the first dynamic image analysis-based feedback control of continuous twin-screw wet granulation process. Granulation of the blend of lactose and starch was selected as a model process. The size and size distribution of the obtained particles were successfully monitored...

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 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...

Roller compaction: Infrared thermography as a PAT for monitoring powder flow from feeding to compaction zone

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Yu, Mingzhe, Omar, Chalak, Weidemann, Marcus, Schmidt, Alexander, Litster, James D., Salman, Agba D.

Roller compaction is a continuous dry granulation process, in which powder is compressed by two counter-rotating rollers. During this process, the powder feeding to the compaction zone has a significant effect on product quality. This work investigates the flow of powder from the feeding zone to...