Estimation of Mass-Based Composition in Powder Mixtures Using Extended Iterative Optimization Technology (EIOT)

09 Jun 2023 | Contributor(s): Shi, Zhenqi, Hermiller, James, García Muñoz, Salvador

The Extended Iterative Optimization Technology (EIOT) method is proposed as an extension to Muteki’s [I&ECR 2013;52 (35):12258–12268] Iterative Optimization Technology to address deviations from Beer–Lambert’s law in powders. The new method estimates the apparent spectrum for the pure species,...

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

09 Jun 2023 | 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...

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....

Ensuring tablet quality via model-based control of a continuous direct compaction process

09 Jun 2023 | Contributor(s): Kirchengast, M, Celikovic, SRehrl, J, Sacher, S, Kruisz, J, Khinast, J, Horn, M

Switching from batch to continuous pharmaceutical production offers several advantages, such as an increased productivity, a steady product quality, and decreased costs. This paper presents a control strategy for direct compaction on a continuous tablet production line consisting of two feeders,...

Enabling precision manufacturing of active pharmaceutical ingredients: workflow for seeded cooling continuous crystallisations

09 Jun 2023 | Contributor(s): Brown, CJ, McGlone, TYerdelen, S, Srirambhatla, V, Mabbott, F, Gurung, R, Briuglia, ML, Ahmed, B, Polyzois, H, McGinty, J, Perciballi, F, Fysikopoulos, D, MacFhionnghaile, P, Siddique, H, Raval, V, Harrington, TS, Vassileiou, AD, Robertson, M, Prasad, E, Johnston, A, Johnston, B, Nordon, A, Srai, JS, Halbert, G, ter, Horst, JH, Price, CJ, Rielly, CD, Sefcik, J, Florence, AJ

Continuous manufacturing is widely used for the production of commodity products. Currently, it is attracting increasing interest from the pharmaceutical industry and regulatory agencies as a means to provide a consistent supply of medicines. Crystallisation is a key operation in the isolation of...

Enabling real time release testing by NIR prediction of dissolution of tablets made by continuous direct compression (CDC)

09 Jun 2023 | Contributor(s): Pawar, Pallavi, Wang, Yifan, Keyvan, Golshid, Callegari, Gerardo, Cuitino, Alberto, Muzzio, Fernando

A method for predicting dissolution profiles of directly compressed tablets for a fixed sustained release formulation manufactured in a continuous direct compaction (CDC) system is presented. The methodology enables real-time release testing (RTRt). Tablets were made at a target drug...

End-to-end continuous manufacturing of conventional compressed tablets: From flow synthesis to tableting through integrated crystallization and filtration

09 Jun 2023 | Contributor(s): Domokos, A, Nagy, BGyurkes, M, Farkas, A, Tacsi, K, Pataki, H, Liu, YC, Balogh, A, Firth, P, Szilagyi, B, Marosi, G, Nagy, ZK

An end-to-end continuous pharmaceutical manufacturing process was developed for the production of conventional direct compressed tablets on a proof-of-concept level for the first time. The output reaction mixture of the flow synthesis of acetylsalicylic acid was crystallized continuously in a...

Dynamic flowsheet model development and sensitivity analysis of a continuous pharmaceutical tablet manufacturing process using the wet granulation route

09 Jun 2023 | Contributor(s): Metta, Nirupaplava, Ghijs, Michael Schäfer, Elisabeth Kumar, Ashish Cappuyns, Philippe Van Assche, Ivo Singh, Ravendra Ramachandran, Rohit De Beer, Thomas, Ierapetritou, Marianthi

In view of growing interest and investment in continuous manufacturing, the development and utilization of mathematical model(s) of the manufacturing line is of prime importance. These models are essential for understanding the complex interplay between process-wide critical process parameters...

Dynamic flowsheet model development and digital design of continuous pharmaceutical manufacturing with dissolution modeling of the final product

09 Jun 2023 | Contributor(s): Nagy, Brigitta, Szilágyi, Botond Domokos, András Vészi, Blanka, Tacsi, Kornélia, Rapi, Zsolt, Pataki, Hajnalka, Marosi, György, Nagy, Zoltán K., Nagy, Zsombor Kristóf

The integration of continuous unit operations imposes a challenge on the pharmaceutical companies aspiring to achieve plant-wide continuous manufacturing due to the additional complexity of the dynamic interactions, process control and quality assurance. To overcome this challenge, flowsheet...

Dynamic Modeling of Encrust Formation and Mitigation Strategy in a Continuous Plug Flow Crystallizer

09 Jun 2023 | Contributor(s): Majumder, Aniruddha, Nagy, Zoltan K.

Encrustation, also known as fouling or scale formation, on the wall of plug flow crystallizers (PFC) can cause major operational and economic problems in pharmaceutical industries. These include increased energy requirements due to increment of thermal resistance and pressure drop, and clogging...

Dynamic Plantwide Modeling, Uncertainty, and Sensitivity Analysis of a Pharmaceutical Upstream Synthesis: Ibuprofen Case Study

09 Jun 2023 | Contributor(s): Montes, Frederico C.C., Gernaey, Krist, Sin, Gürkan

A dynamic plantwide model was developed for the synthesis of the active pharmaceutical ingredient (API) ibuprofen, following the Hoescht synthesis process. The kinetic parameters, reagents, products, and byproducts of the different reactions were adapted from literature, and the different process...

Effect of material properties on the residence time distribution (RTD) of a tablet press feed frame

09 Jun 2023 | Contributor(s): Furukawa, Ryoichi, Singh, Ravendra, Ierapetritou, Marianthi

In continuous manufacturing (CM) of pharmaceutical tablets, the residence time distribution (RTD) of the tablet press feed frame plays an important role in ensuring the critical quality attributes (CQAs) of the final product. Knowledge of factors affecting the RTD of the feed frame is necessary...

Early detection of capping risk in pharmaceutical compacts

09 Jun 2023 | Contributor(s): Xu, Xiaochi, Vallabh, Chaitanya Krishna Prasad, Hoag, Stephen W., Dave, Vivek S., Cetinkaya, Cetin

Capping is a common mechanical defect in tablet manufacturing, exhibited during or after the compression process. Predicting tablet capping in terms of process variables (e.g. compaction pressure and speed) and formulation properties is essential in pharmaceutical industry. In current work, a...

Effective Development of PAT Capability in Pharmaceutical Manufacturing

09 Jun 2023 | Contributor(s): Hammond, Steve

Over the last ten years, the path to effective development of PAT has evolved, driven by the advent of continuous manufacturing. The development and deployment of PAT used for pharmaceutical manufacturing has arrived at a point where application development has been miniaturized and streamlined....

Digital Design of the Crystallization of an Active Pharmaceutical Ingredient Using a Population Balance Model with a Novel Size Dependent Growth Rate Expression. From Development of a Digital Twin to In Silico Optimization and Experimental Validation

09 Jun 2023 | Contributor(s): Szilágyi, Botond, Eren, Ayşe Quon, Justin L. Papageorgiou, Charles D., Nagy, Zoltán K.

Prediction and control of the product properties in crystallization processes are practical challenges in the pharmaceutical industry. Effective crystallization process design and operation techniques are needed to meet the critical quality attributes (CQAs) and minimize batch-to-batch variation....

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....

Direct compaction: An update of materials, trouble-shooting, and application

09 Jun 2023 | Contributor(s): Li, Z, Zhao, LJLin, X, Shen, L, Feng, Y

Direct compaction (DC) is the preferred choice for tablet manufacturing; however, only less than 20% of active pharmaceutical ingredients could be compacted via DC as its high requirement for functional properties of materials. Materials with improper functionalities could lead to serious...

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....

Development of a tablet press feed frame lead lag determination model using in-line and off-line NIR measurements

09 Jun 2023 | Contributor(s): Van;Hauwermeiren, D, Peeters, MPeeters, E, Cogoni, G, Yang, LA, De;Beer, T

For continuous pharmaceutical manufacturing of oral solid dosages, it is essential that product quality is measured inline. In this application, a continuous rotary tablet press is used. The goal is a model-based assessment of the quality of the blend in the feed frame to determine whether the...

Development of immediate release 3D-printed dosage forms for a poorly water-soluble drug by fused deposition modeling: Study of morphology, solid state and dissolution

09 Jun 2023 | Contributor(s): Fanous, M, Bitar, MGold, S, Sobczuk, A, Hirsch, S, Ogorka, J, Imanidis, G

3D-printing technologies such as Fused Deposition Modeling (FDM) bring a unique opportunity for personalized and flexible near-patient production of pharmaceuticals, potentially improving safety and efficacy for some medications. However, FDM-printed tablets often exhibit tendency for slow...

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 calibration-free/minimal calibration wavelength selection for iterative optimization technology algorithms toward process analytical technology application

09 Jun 2023 | Contributor(s): Rish, AJJ, Henson, Samuel R., Anik Alam, Md., Liu, Yang, Drennen, James K., Anderson, Carl A

As continuous manufacturing (CM) processes are developed, process analytical technology (PAT) via NIR spectroscopy has become an integral tool in process monitoring. NIR spectroscopy requires the deployment of complex multivariate models to extract the relevant information. The model of choice...

Development of a tablet press feed frame lead lag determination model using in-line and off-line NIR measurements

09 Jun 2023 | Contributor(s): Van;Hauwermeiren, D, Peeters, MPeeters, E, Cogoni, G, Yang, LA, De;Beer, T

For continuous pharmaceutical manufacturing of oral solid dosages, it is essential that product quality is measured inline. In this application, a continuous rotary tablet press is used. The goal is a model-based assessment of the quality of the blend in the feed frame to determine whether the...

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

09 Jun 2023 | 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...