A review of PAT strategies in secondary solid oral dosage manufacturing of small molecules

09 Jun 2023 | Contributor(s): Laske, Stephan, Paudel, Amrit, Scheibelhofer, Otto, Sacher, Stephan, Hoermann, Theresa, Khinast, Johannes, Kelly, Adrian, Rantannen, Jukka, Korhonen, Ossi, Stauffer, Fanny, De Leersnyder, Fien, De Beer, Thomas, Mantanus, Jerome, Chavez, Pierre-Francois, Thoorens, Benjamin, Ghiotti, Patrizia, Schubert, Martin, Tajarobi, Pirjo, Haeffler, Gunnar, Lakio, Satu, Fransson, Magnus, Sparen, Anders, Abrahmsen-Alami, Susanna, Folestad, Staffan, Funke, Adrian, Backx, Ivo, Kavsek, Barbara, Kjell, Francois, Michaelis, Marc, Page, Trevor, Palmer, John, Schaepman, Alexander, Sekulic, Sonja, Hammond, Steve, Braun, Birgit, Colegrove, Brenda

Pharmaceutical solid oral dosage product manufacturing is a well-established, yet revolutionizing area. To this end, process analytical technology (PAT) involves interdisciplinary and multivariate (chemical, physical, microbiological and mathematical) methods for material (e.g. materials,...

A sampling system for flowing powders based on the theory of sampling

09 Jun 2023 | Contributor(s): Alvarado-Hernández, Bárbara B, Sierra-Vega, Nobel O, Martínez-Cartagena, Pedro, Hormaza, Manuel, Méndez, Rafael, Romañach, Rodolfo J.

An innovative chute and stream sampler system for flowing powders has been developed and tested. The system is designed for representative sampling based on the principles of the Theory of Sampling (TOS). The sampling system was used in combination with near infrared (NIR) spectroscopy to...

An Innovative Sampling Interface for Monitoring Flowing Pharmaceutical Powder Mixtures

09 Jun 2023 | Contributor(s): Martínez-Cartagena, Pedro, Romañach, Rodolfo J., Sierra-Vega, Nobel O; Alvarado-Hernández, Bárbara B; Méndez, Rafael

A chute was designed following the principles of the Theory of Sampling to minimize the variations in powder flow and provide all particles in the flowing blends with the same opportunity of being selected as a sample. The design also reduces the thickness of the chute to allow the analysis of a...

Analysis of powder phenomena inside a Fette 3090 feed frame using in-line NIR spectroscopy

09 Jun 2023 | Contributor(s): Mateo-Ortiz Daniel, Colon, Yleana, Romañach, Rodolfo, Mendez, Rafael

New analytical methods are needed to understand and optimize the processes by which tablets are produced. Fette 3090 tablet presses are commonly used in the pharmaceutical industry. A near-infrared (NIR) probe was installed into a Fette 3090 feed frame to understand and monitor the die filling...

Assessment of Robustness for a Near-Infrared Concentration Model for Real-Time Release Testing in a Continuous Manufacturing Process

09 Jun 2023 | Contributor(s): Colon, Yleana, Vargas, Jenny, Sánchez, Eric, Navarro, Gilfredo, Romañach, Rodolfo

This study describes the robustness test of a transmission near-infrared spectroscopic (NIRS) model for prediction of drug concentration in core tablets as part of real-time release testing (RTRt) efforts for a continuous manufacturing process. Seven calibration blend samples were prepared...

Challenges, opportunities and recent advances in near infrared spectroscopy applications for monitoring blend uniformity in the continuous manufacturing of solid oral dosage forms

09 Jun 2023 | Contributor(s): Velez, Natasha L., Drennen, James K., Anderson, Carl A.

Near infrared (NIR) spectroscopy has been widely recognized as a powerful PAT tool for monitoring blend uniformity in continuous manufacturing (CM) processes. However, the dynamic nature of the powder stream and the fast rate at which it moves, compared to batch processes, introduces challenges...

Characterization of Near-Infrared and Raman Spectroscopy for In-Line Monitoring of a Low-Drug Load Formulation in a Continuous Manufacturing Process

09 Jun 2023 | Contributor(s): Harms, Zachary, Shi, Zhenqi: Kulkarni, Rajesh, Myers, David P.

Reflectance spectroscopy is an excellent candidate for process analytical technology (PAT) applications in continuous manufacturing of pharmaceutical tablets. Spectroscopic methods provide a real-time, nondestructive measurement of the active pharmaceutical ingredient (API) concentration in order...

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...

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

09 Jun 2023 | 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 quantitative monitoring of powder mixing dynamics by near-infrared spectroscopy

09 Jun 2023 | Contributor(s): Koller, DM, Posch, A, Horl, G, Voura, C, Radl, S, Urbanetz, N, Fraser, SD, Tritthart, W, Reiter, F, Schlingmann, M, Khinast, JG

FT-NIR spectroscopy with a fiber optical reflection probe was applied as a process analytical technology tool for the continuous quantitative in-line monitoring of pharmaceutical powder mixing processes in a bladed mixer. Two powders, acetyl salicylic acid as an active pharmaceutical ingredient...

Control of three different continuous pharmaceutical manufacturing processes: Use of soft sensors

09 Jun 2023 | Contributor(s): Rehrl, J, Karttunen, APNicolai, N, Hormann, T, Horn, M, Korhonen, O, Nopens, I, De, Beer, T, Khinast, JG

One major advantage of continuous pharmaceutical manufacturing over traditional batch manufacturing is the possibility of enhanced in-process control, reducing out-of-specification and waste material by appropriate discharge strategies. The decision on material discharge can be based on the...

Development of an In-Line Near-Infrared Method for Blend Content Uniformity Assessment in a Tablet Feed Frame

09 Jun 2023 | Contributor(s): Li, Yi, Anderson, Carl A, Drennen, James K, Airiau, Christian, Igne, Benoît

Process analytical technology (PAT) has shown great potential for in-line tableting process monitoring. The study focuses on the development and validation of an in-line near-infrared (NIR) spectroscopic method for the determination of content uniformity of blends in a tablet feed frame. An...

Development of near infrared spectroscopic calibration models for in-line determination of low drug concentration, bulk density, and relative specific void volume within a feed frame

09 Jun 2023 | Contributor(s): Ortega-Zuñiga, Carlos, Pinzón-De la Rosa, Carlos, Román-Ospino, Andrés D., Serrano-Vargas, Alberto, Romañach, Rodolfo J., Mendez, Rafael

This study describes the development of a near infrared (NIR) calibration model for real time determination of drug concentration, powder density, and porosity or relative specific void volume (RSVV) of 3.00%w/w acetaminophen blends within a feed frame. The NIR calibration model was developed...

Development of Near Infrared Spectroscopy-based Process Monitoring Methodology for Pharmaceutical Continuous Manufacturing Using an Offline Calibration Approach

09 Jun 2023 | Contributor(s): Hetrick, Evan, Barnes, Lukas E, Garrett, Aaron W, Rupard, Robert G, Kramer, Timothy T, Cooper, Tony M, Myers, David P, Shi, Zhenqi, Castle, Bryan C

A near-infrared (NIR) calibration was developed using an efficient offline approach to enable a quantitative partial least-squares (PLS) chemometric model to measure and monitor the concentration of active pharmaceutical ingredients (API) in powder blends in the feed frame (FF) of a tablet press....

Dry Powder Mixing Is Feasible in Continuous Twin Screw Extruder: Towards Lean Extrusion Process for Oral Solid Dosage Manufacturing

09 Jun 2023 | Contributor(s): Mateo-Ortiz, Daniel, Villanueva-Lopez, Vladimir, Muddu, Shashank Venkat, Doddridge, Gregory D., Alhasson, Dana, Dennis, Michael C.

Using discrete element method (DEM) modeling and near-infrared (NIR) spectroscopy, the feasibility of powder mixing in the initial pre-melting zones of a twin screw extruder using two independent feeders was studied. Previous work in the pharmaceutical and food industry has focused on mixing when...

Evaluation of Analytical and Sampling Errors in the Prediction of the Active Pharmaceutical Ingredient Concentration in Blends From a Continuous Manufacturing Process

09 Jun 2023 | Contributor(s): Vargas, Jenny, Roman-Ospino, Andres, Sanchez, Eric, Romañach, Rodolfo

Purpos: A near-infrared (NIR) spectroscopic method was developed for real time analysis of the active pharmaceutical ingredient (API) in blends from a continuous manufacturing process. The sampling and analytical errors of these determinations were estimated through variographic analysis....

Evaluation of three approaches for real-time monitoring of roller compaction with near-infrared spectroscopy

09 Jun 2023 | Contributor(s): Acevedo, D., Muliadi, A., Giridhar, A., Litster, J. D., Romañach, R. J.

Three different approaches have been evaluated for monitoring ribbon density through real-time near-infrared spectroscopy measurements. The roll compactor was operated to produce microcrystalline cellulose (MCC) ribbons of varying densities. The first approach used the slope of the spectra which...

Fit-for-Purpose Miniature NIR Spectroscopy for Solid Dosage Continuous Manufacturing

09 Jun 2023 | Contributor(s): Karry, Krizia, Singh, Ravendra, Muzzio, Fernando

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 | 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 monitoring of the powder flow behavior and drug content in a Fette 3090 feed frame at different operating conditions using Near Infrared spectroscopy

09 Jun 2023 | Contributor(s): Sierra-Vega, Nobel, Sánchez-Paternina, Adriluz, Maldonado, Nadja, Cárdenas, Vanessa, Romañach, Rodolfo, Mendez, Rafael

Near infrared (NIR) spectroscopy was used to determine the drug concentration in 3% (w/w) acetaminophen blends within the complex flow regime of the tablet press feed frame just before tablet compaction. NIR spectra also provided valuable information on the powder flow behavior within the feed...

In-line monitoring of low drug concentration of flowing powders in a new sampler device

09 Jun 2023 | Contributor(s): Sierra-Vega, Nobel O, Méndez, Rafael, Martínez-Cartagena, Pedro; Alvarado-Hernández, Bárbara B; Romañach, Rodolfo J.

A novel sampler device for flowing powders was tested to quantify drug concentrations as low as 0.76% w/w in pharmaceutical powder blends. The sampler device was developed based on the powder flow behavior within a tablet press feed frame, following the principles laid down in the Theory of...

In-line monitoring of the drug content of powder mixtures and tablets by near-infrared spectroscopy during the continuous direct compression tableting process

09 Jun 2023 | Contributor(s): Järvinen, Kristiina, Hoehe, Wolfgang, Järvinen, Maiju, Poutiainen, Sami, Juuti, Mikko, Borchert, Sven

Continuous manufacturing methods offer economic and quality advantages when compared with batch manufacturing methods. In continuous manufacturing, one requires real time assurance of quality of product via the implementation of PAT tools. This study focuses on an in-line near-infrared (NIR)...

Near Infrared Method Development for a Continuous Manufacturing Blending Process

09 Jun 2023 | Contributor(s): Colon, Yleana, Florian, Miguel, Acevedo, David, Mendez, Rafael, Romañach, Rodolfo

Purpose This study describes the validation of a near infrared spectroscopic method for monitoring a continuous manufacturing system. The achievement of this goal requires determining the near infrared (NIR) method’s accuracy, precision, obtaining an estimate of the sample volume analyzed, and...

Near-infrared spectroscopic applications in pharmaceutical particle technology

09 Jun 2023 | 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...

Near-infrared Spectroscopy for the In-line Characterization of Powder Voiding Part I: Development of the Methodology

09 Jun 2023 | Contributor(s): Ropero, Jorge, Beach, Lauren, Alcala, Manel, Rentas, Raizza, Dave, Rajesh N., Romanach, Rodolfo J.

In-line near-infrared spectroscopy (NIR) spectra were acquired and analyzed to assess the relationship between physical and chemical properties of voiding powders and their spectral changes. NIR spectra were obtained for powders voiding from a conical glass funnel while the powder flow was...