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...

Dual chamber cartridges in a continuous pharmaceutical freeze-drying concept: Determination of the optimal dynamic infrared heater temperature during primary drying

09 Jun 2023 | Contributor(s): De Meyer, Laurens, Lammens, Joris, Vanbillemont, Brecht, Van Bockstal, Pieter Jan, Corver, Jos, Vervaet, Chris, Friess, Wolfgang, De Beer, Thomas

The applicability of DCCs in a continuous freeze-drying concept based on spin freezing and infrared heating was evaluated. Maximum applicable filling volume was evaluated. Secondly the mechanistic model for the determination of the optimal dynamic infrared heater temperature during primary drying...

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 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 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...

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 continuous crystallization processes using a single-stage mixed-suspension, mixed-product removal crystallizer with recycle

09 Jun 2023 | Contributor(s): Wong, Shin Yee, Tatusko, Adam P. Trout, Bernhardt L., Myerson, Allan S. ;

An ideal pharmaceutical crystallization process produces a pure product at a high yield while minimizing energy input, the process equipment footprint, and its complexity. A good candidate for such a process is a single-stage mixed-suspension, mixed-product removal (MSMPR) crystallizer with...

Development of Continuous Filtration in a Novel Continuous Filtration Carousel Integrated with Continuous Crystallization

09 Jun 2023 | Contributor(s): Liu, Yiqing C., Domokos, András, Coleman, Simon, Firth, Paul, Nagy, Zoltan K.

Pharmaceutical manufacturing has been largely carried out in batch mode, which has disadvantages such as batch-to-batch variations and difficult scale-up. As a result, the pharmaceutical industry is going through the paradigm shift to continuous manufacturing. Many unit operations have been...

Development of directly compressible powders via co-spray drying

09 Jun 2023 | Contributor(s): Gonnissen, Y., Remon, J. P., Vervaet, C.

Continuous production of directly compressible powders was achieved by coprocessing acetaminophen and carbohydrates via spray drying. Binary and ternary powder mixtures containing drug substance and carbohydrates were prepared by co-spray drying and evaluated on spray drying processibility,...

Development of drying-induced stresses in pharmaceutical granules prepared in continuous production line

09 Jun 2023 | Contributor(s): Mezhericher, Maksim

The phenomenon of development of drying-induced stresses has been given a through consideration in the literature on drying of many products. At the same time, to the best of our knowledge, the open published sources contain no information on drying stresses in pharmaceutical granules prepared by...

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 Maltodextrin-Based Immediate-Release Tablets Using an Integrated Twin-Screw Hot-Melt Extrusion and Injection-Molding Continuous Manufacturing Process

09 Jun 2023 | Contributor(s): Puri, Vibha, Brancazio, Dave, Desai, Parind M., Jensen, Keith D., Chun, Jung-Hoon, Myerson, Allan S., Trout, Bernhardt L.

The combination of hot-melt extrusion and injection molding (HME-IM) is a promising process technology for continuous manufacturing of tablets. However, there has been limited Research Article on its application to formulate crystalline drug-containing immediate-release tablets. Furthermore,...

Development and implementation of an advanced model predictive control system into continuous pharmaceutical tablet compaction process

09 Jun 2023 | Contributor(s): Bhaskar, Aparajith, Barros, Fernando N, Singh, Ravendra

In the context of continuous pharmaceutical oral dosage manufacturing, a control system is essential to ensure that the critical quality attributes (CQAs) are maintained within the regulatory constraints by mitigating variations generated in upstream operations. Such a system is essential to the...

Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities)

09 Jun 2023

Guideline establishes reuqirements for the synthesis/production of API in primary pharmaceutical manufacturing.

Development and Optimization of a Wet Granulation Process at Elevated Temperature for a Poorly Compactible Drug Using Twin Screw Extruder for Continuous Manufacturing

09 Jun 2023 | Contributor(s): Meena, Anuprabha K, Desai, Divyakant, Serajuddin,, Abu T. M.

The objective of this study was to enhance tabletability of a poorly compactible drug, acetaminophen, by wet granulation using twin screw extruder at high temperature. It was desired that there would be minimum amounts of excipients used and the granules obtained after extrusion would be dry and...

Development and Scale-Up of a Continuous Aerobic Oxidative Chan-am Coupling

09 Jun 2023 | Contributor(s): Brewer, AC, Hoffman, PCMartinelli, JR, Kobierski, ME, Mullane, N, Robbins, D

Despite the benefits of high atom economy and low cost, aerobic oxidations have found limited use in the synthesis of active pharmaceutical ingredients (APIs) because of safety concerns and poor selectivity. In this report, the design, development, and scale-up of a continuous, high pressure...

Development and Scale-Up of Diversion Strategy for Twin Screw Granulation in Continuous Manufacturing

09 Jun 2023 | Contributor(s): Pawar, Pallavi, Clancy, Don, Gorringe, Lee, Barlow, Steve, Hesketh, Alex, Elkes, Richard

Successful implementation of Continuous Manufacturing technology requires real time product quality monitoring that can result into rejection strategies for material manufactured outside process control limits. In a twin screw granulation process, parameters like water content, powder feed rate,...

Development and Use of a Residence Time Distribution (RTD) Model Control Strategy for a Continuous Manufacturing Drug Product Pharmaceutical Process

09 Jun 2023 | Contributor(s): Hurley, Samantha, Tantuccio, Anthony, Escotet-Espinoza, Manuel Sebastian, Flamm, Matthew, Metzger, Matthew

Residence-time-distribution (RTD)-based models are key to understanding the mixing dynamics of continuous manufacturing systems. Such models can allow for material traceability throughout the process and can provide the ability for removal of non-conforming material from the finished product....

Development and validation of an in-line NIR spectroscopic method for continuous blend potency determination in the feed frame of a tablet press

09 Jun 2023 | Contributor(s): De Leersnyder, Fien, Peeters, Elisabeth, Djalabi, Hasna, Vanhoorne, Valérie, Van Snick, Bernd, Hong, Ke, Hammond, Stephen, Liu, Angela, Ziemons, Eric, Vervaet, Chris, De Beer, Thomas

A calibration model for in-line API quantification based on near infrared (NIR) spectra collection during tableting in the tablet press feed frame was developed and validated. First, the measurement set-up was optimised and the effect of filling degree of the feed frame on the NIR spectra was...

Development of a continuous direct compression platform for low-dose drug products

09 Jun 2023 | Contributor(s): Van Snick, B, Holman, J, Vanhoorne, V, Kumar, A, De Beer, T, Remon, JP, Vervaet, C

In this work a continuous direct compression process was developed for a low-dosed drug product. Each unit operation of the GEA CDC-50 system was thoroughly investigated. This paper aimed to tackle the macroscopic and microscopic blend uniformity challenges inherently associated with continuous...

Development of a Controlled Continuous Low-Dose Feeding Process

09 Jun 2023 | Contributor(s): Fathollahi, Sara, Kruisz, Julia, Sacher, Stephan, Rehrl, Jakob, Escotet-Espinoza, M. Sebastian, DiNunzio, James, Glasser, Benjamin J., Khinast, Johannes G.

This paper proposes a feed rate control strategy for a novel volumetric micro-feeder, which can accomplish low-dose feeding of pharmaceutical raw materials with significantly different powder properties. The developed feed-forward control strategy enables a constant feed rate with a minimum...

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

09 Jun 2023 | 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...

Development of a Novel Continuous Filtration Unit for Pharmaceutical Process Development and Manufacturing

09 Jun 2023 | Contributor(s): Ottoboni, S, Price, CJSteven, C, Meehan, E, Barton, A, Firth, P, Mitchell, A, Tahir, F

The lack of a commercial laboratory, pilot and small manufacturing scale dead end continuous filtration and drying unit it is a significant gap in the development of continuous pharmaceutical manufacturing processes for new active pharmaceutical ingredients (APIs). To move small-scale...

Designs of continuous-flow pharmaceutical crystallizers: developments and practice

09 Jun 2023 | Contributor(s): Jiang, Mo, Braatz, Richard D.

Crystallization is an effective, low-cost purification & formulation process widely applied to pharmaceuticals and fine chemicals. This review describes recent advances in Research Article on lab-scale solution-based continuous crystallization, including (1) a 5-step general design procedure; (2)...

Detailed Analysis of the Online Near-Infrared Spectra of Pharmaceutical Blend in a Rotary Tablet Press Feed Frame

09 Jun 2023 | Contributor(s): Šašić, Slobodan, Blackwood, Daniel, Liu, Angela, Ward, Howard W, Clarke, Hugh

The present study is an in-depth analysis of the online near-infrared (NIR) spectra acquired with a spectrometer mounted on the rotary tablet press feed frame. A 3.5% active pharmaceutical ingredient (API) formulation is analyzed. An attempt is made to determine the API univariately via the 2nd...