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...

Development of a novel method for the continuous blending of carrier-based dry powders for inhalation using a co-rotating twin-screw extruder

23 Jul 2024 | Contributor(s): Spahn, Jamie E., Hefnawy, Amr, Smyth, Hugh D. C., Zhang, Feng

Twin-screw extruders are useful in tuning certain product characteristics due to the ability to greatly modify screw profiles as well as operating parameters. However, their use has not yet been applied to dry powder inhalation. In this study the feasibility of using a twin-screw extruder to...

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 an Organometallic Flow Chemistry Reaction at PilotPlant Scale for the Manufacture of Verubecestat

25 Jun 2024 | Contributor(s): Thaisrivongs, David A., Naber, John R., Rogus, Nicholas J., Spencer, Glenn

We report the development of an organolithium addition to a chiral ketimine at pilot-plant scale using flow chemistry. Given the mixing sensitivity of this process, established previously at both lab and kilogram scale, we conducted critical experiments to understand the impact of flow rate,...

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 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....

Development of Pilot-Scale Continuous Production of an LY2886721 Starting Material by Packed-Bed Hydrogenolysis

25 Jun 2024 | Contributor(s): Zaborenko, Nikolay, Linder, Ryan J., Braden, Timothy M., Campbell, Bradley M., Hansen, Marvin M., Johnson, Martin D.

The design, development, and implementation of a pilot-scale continuous hydrogenolysis in a catalytic packed bed to generate a starting material is described. Control of a critical defluorination impurity under the reaction conditions has been achieved by reducing residence time inside the...

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....

Diminished segregation in continuous powder mixing

09 Jun 2023 | Contributor(s): Oka, S, Sahay, A, Meng, W, Muzzio, F

Binary powder mixtures with variable segregation tendencies were mixed in a tumbling batch blender and in a continuous convective tubular blender. The degree of homogeneity of the final blend obtained from the continuous blender was found to be much higher than that from the batch V-blender, for...

Direct compaction properties of Zingiberis Rhizoma extracted powders coated with various shell materials: Improvements and mechanism analysis

09 Jun 2023 | Contributor(s): Li, Zhe, Zhou, Miaomiao, Wu, Fei, Shen, Lan, Lin, Xiao, Feng, Yi

Direct compaction (DC) attracts more and more attention for tablet manufacturing; however, its application in natural plant product (NPP) tablets is still extremely limited. In this study, 8 kinds of composite particles (CPs) based on the Zingiberis Rhizoma extracted powder (ZR) (a natural plant...

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...

Discovery and mechanistic study of a photocatalytic indoline dehydrogenation for the synthesis of elbasvir

25 Jun 2024 | Contributor(s): Susanne, Flavien, Martin, Benjamin, Aubry, Michel, Sedelmeier, Joerg, Lima, Fabio, Sevinc, Serbuelent, Piccioni, Lorenzo, Haber, Julien, Schenkel, Berthold, Venturoni, Francesco

Elbasvir is a potent NS5A antagonist for the treatment of chronic hepatitis C. A seemingly trivial indoline oxidation en route to the target compound was complicated by epimerization of a stereogenic hemiaminal center under most standard oxidation conditions. To address this issue, a novel...

Double-Track Electrochemical Green Approach for Simultaneous Dissolution Profiling of Naproxen Sodium and Diphenhydramine Hydrochloride

09 Jun 2023 | Contributor(s): Shehata, MA, Fawaz, EMAbd, El-Rahman, MK, Abdel-Moety, EM

Acquisition of the dissolution profiles of more than single active ingredient in a multi-analyte pharmaceutical formulation is a mandatory manufacturing practice that is dominated by utilization of the off-line separation-based chromatographic methods. This contribution adopts a new...

Downstream processing from melt granulation towards tablets: In-depth analysis of a continuous twin-screw melt granulation process using polymeric binders

09 Jun 2023 | Contributor(s): Grymonpre, W., Verstraete, G., Vanhoorne, V., Remon, J. P., De Beer, T., Vervaet, C.

The concept of twin-screw melt granulation (TSMG) has steadily (re)-gained interest in pharmaceutical formulation development as an intermediate step during tablet manufacturing. However, to be considered as a viable processing option for solid oral dosage forms there is a need to understand all...

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...