The Use of Near-Infrared and Microwave Resonance Sensing to Monitor a Continuous Roller Compaction Process

09 Jun 2023 | Contributor(s): Austin, John, Gupta, Anshu, Mcdonnell, Ryan, Reklaitis, Gintaras V., Harris, Michael T

Roller compaction is commonly used in the pharmaceutical and nutraceutical industries to increase and narrow the size distribution of a particulate material, making it easier to process. Both the moisture content of the material and the density of the roller compacted ribbon affect the uniformity...

The Use of PAT and Off-line Methods for Monitoring of Roller Compacted Ribbon and Granule Properties with a View to Continuous Processing

09 Jun 2023 | Contributor(s): McAuliffe M.A.P., Omahony G.E., Blackshields C.A., Collins J.A., Egan D.P., Kiernan L., Oneill E., Lenihan S., Walker G.M., Crean A.M.

Real-time process monitoring using process analytical technology (PAT) tools can augment process understanding, enable improved process control, and hence facilitate the production of high-quality pharmaceutical products. While beneficial for batch processes, the availability of PAT tools to...

The development of an inline Raman spectroscopic analysis method as a quality control tool for hot melt extruded ramipril fixed-dose combination products

09 Jun 2023 | Contributor(s): Andres, G.P., Jones D.S., Senta-Loys Z., Almajaan A., Li S., Chevallier O., Elliot C., Healy A.M., Kelleher J.F., Madi A.M., Gilvary G.C., Tian Y.a

Currently in the pharmaceutical industry, continuous manufacturing is an area of significant interest. In particular, hot-melt extrusion (HME) offers many advantages and has been shown to significantly reduce the number of processing steps relative to a conventional product manufacturing line. To...

The effect of lubrication on density distributions of roller compacted ribbons

09 Jun 2023 | Contributor(s): Miguelez-Moran, A. M, Seville, J. P. K.

Roller compaction is a continuous dry granulation process for producing free flowing granules in order to increase the bulk density and uniformity of pharmaceutical formulations. It is a complicated process due to the diversity of powder blends and processing parameters involved. The properties...

The Effect of Mixer Properties and Fill Level on Granular Flow in a Bladed Mixer

09 Jun 2023 | Contributor(s): Remy, B, Glasser, BJ, Khinast, JG

The discrete element method was used to study the effect of mixer properties and fill level oil the granular flow of monodisperse, cohesionless spheres in a bladed mixer. For fill levels just covering the span of the blades, a three-dimensional (3-D) recirculation zone develops in front of the...

The effect of screw configuration and formulation variables on liquid requirements and granule quality in a continuous twin screw wet granulation process

09 Jun 2023 | Contributor(s): Vandevivere, L., Van Wijmeersch, E., Hausler, O., De Beer, T., Vervaet, C., Vanhoorne, V.

The effect of two screw configurations with varying stagger angle was evaluated on the liquid amount required to produce good quality granules for a highly (mannitol-based) and a poorly (DCP-based) soluble formulation containing different binders. It is generally known that the use of a higher...

The Effect of Ultrasound on the Crystallisation of Paracetamol in the Presence of Structurally Similar Impurities

09 Jun 2023 | Contributor(s): Nguyen, TTH, Khan, ABruce, LM, Forbes, C, O'Leary, RL, Price, CJ

Sono-crystallisation has been used to enhance crystalline product quality particularly in terms of purity, particle size and size distribution. In this work, the effect of impurities and ultrasound on crystallisation processes (nucleation temperature, yield) and crystal properties (crystal size...

The effects of unintentional and intentional process disturbances on tablet quality during long continuous manufacturing runs

09 Jun 2023 | Contributor(s): Taipale-Kovalainen, Krista, Karttunen, Anssi-Pekka, Niinikoski, Hannes, Ketolainen, Jarkko, Korhonen, Ossi

Several kinds of process disturbances can occur during (continuous) tablet manufacturing, i.e. unintentional or intentional disturbances. Long run-time continuous manufacturing studies are used to investigate the effects of intentional and unintentional deviations. In this study, the horizontal...

The Evolving State of Continuous Processing in Pharmaceutical API Manufacturing: A Survey of Pharmaceutical Companies and Contract Manufacturing Organizations

09 Jun 2023 | Contributor(s): McWilliams, JC, Allian, ADOpalka, SM, May, SA, Journet, M, Braden, TM

This manuscript provides the results of an in-depth survey assessment of the capabilities, experience, and perspectives on continuous processing in the pharmaceutical sector, with respondents from both pharmaceutical companies and Contract Manufacturing Organizations (CMOs). The survey includes...

The Future of Pharmaceutical Manufacturing Sciences

09 Jun 2023 | Contributor(s): Rantanen, Jukka, Khinast Johannes

The entire pharmaceutical sector is in an urgent need of both innovative technological solutions and fundamental scientific work, enabling the production of highly engineered drug products. Commercial-scale manufacturing of complex drug delivery systems (DDSs) using the existing technologies is...

The impact of channel fill level on internal forces during continuous twin screw wet granulation

09 Jun 2023 | Contributor(s): Torrecillas, Carlota Mendez, Gorringe, Lee J., Rajoub, Nazer, Robertson, John, Elkes, Richard G., Lamprou, Dimitrios A., Halbert, Gavin W

The forces experienced by the particles inside a twin screw granulator (TSG) are one of the most difficult parameters to measure quantitatively. However, it is possible to perform accurately this measurement through the use of dye containing calibrated microencapsulated sensors (LAMES) whose...

Technoeconomic optimisation and comparative environmental impact evaluation of continuous crystallisation and antisolvent selection for artemisinin recovery

09 Jun 2023 | Contributor(s): Jolliffe, HG, Gerogiorgis, DI

Systematic nonlinear optimisation is a valuable tool towards evaluating the performance of conceptual Continuous Pharmaceutical Manufacturing (CPM) flowsheets. This study considers total cost minimisation of multiple plausible design choices and eight candidate antisolvents for the continuous...

Technoeconomic Optimization of a Conceptual Flowsheet for Continuous Separation of an Analgaesic Active Pharmaceutical Ingredient (API)

09 Jun 2023 | Contributor(s): Jolliffe, HG, Gerogiorgis, DI

Continuous Pharmaceutical Manufacturing (CPM) has recently emerged as a promising alternative to current batch production methods, which require significant expenditures in order to ensure product quality and process reliability. Advances in new continuous synthesis routes, demonstrations of full...

Technoeconomic Optimization of Continuous Crystallization for Three Active Pharmaceutical Ingredients: Cyclosporine, Paracetamol, and Aliskiren

09 Jun 2023 | Contributor(s): Diab, S, Gerogiorgis, DI

Mixed suspension, mixed product removal (MSMPR) crystallizers are widely implemented for the continuous crystallization of active pharmaceutical ingredients (APIs), allowing enhanced efficiency, flexibility, and product quality compared to currently dominant batch crystallizer designs....

Template-induced nucleation for controlling crystal polymorphism: from molecular mechanisms to applications in pharmaceutical processing

09 Jun 2023 | Contributor(s): Parambil, JV, Poornachary, SKHeng, JYY, Tan, RBH

Over the last two decades, the use of template surfaces to induce heterogeneous crystal nucleation has been explored primarily to address two different goals: first, as an alternative to the conventional seeding technique used for polymorph control and, second, as a technique to promote the...

The A Priori Design and Selection of Ionic Liquids as Solvents for Active Pharmaceutical Ingredients

09 Jun 2023 | Contributor(s): Kunov-Kruse, AJ, Weber, CCRogers, RD, Myerson, AS

In this paper we derive a straightforward computational approach to predict the optimal ionic liquid (IL) solvent for a given compound, based on COSMO-RS calculations. These calculations were performed on 18 different active pharmaceutical ingredients (APIs) using a matrix of 210 hypothetical...

The Application of an Automated Control Strategy for an Integrated Continuous Pharmaceutical Pilot Plant

09 Jun 2023 | Contributor(s): Lakerveld, R, Benyahia, BHeider, PL, Zhang, HT, Wolfe, A, Testa, CJ, Ogden, S, Hersey, DR, Mascia, S, Evans, JMB, Braatz, RD, Barton, PI

Continuous manufacturing offers potential opportunities for the improved manufacturing of pharmaceutical products. A key challenge is the development of an appropriate control strategy. The experimental application of an automated control strategy is presented for an end-to-end continuous...

The Changing Face of Process Development & Chemical Manufacturing - A View from the Regulators on Continuous Manufacturing

09 Jun 2023 | Contributor(s): Wiles, Charolotte

Industry wide there is a drive for resource efficiency and flexibility, to adapt quickly in what is increasingly becoming a volatile, changing marketplace. As the ‘patent cliff’ looms for many high-volume API’s, there is also a shift away from blockbusters towards lower volume, higher potency...

The Common Technical Document for the Registration of Pharmaceuticals for Human Use: Quality - M4Q(R1)

09 Jun 2023

Guideline aims to harminze the approach to the eCTD to create efficiencies for reviewers and decrease the rejection rate for drug applications.

The Concept of Chemical Generators: On-Site On-Demand Production of Hazardous Reagents in Continuous Flow

09 Jun 2023 | Contributor(s): Dallinger, D, Gutmann, B, Kappe, CO

CONSPECTUS: In recent years, a steadily growing number of chemists, from both academia and industry, have dedicated their Research Article to the development of continuous flow processes performed in milli- or microreactors. The common availability of continuous flow equipment at virtually all...

The Current Scientific and Regulatory Landscape in Advancing Integrated Continuous Biopharmaceutical Manufacturing

09 Jun 2023 | Contributor(s): Adam C Fisher, Mark-Henry Kamga, Cyrus Agarabi, Kurt Brorson, Sau L Lee, Seongkyu Yoon

There is a trend across the pharmaceutical sector toward process intensification and continuous manufacturing to produce small-molecule drugs or biotechnology products. For biotechnology products, advancing the manufacturing technology behind upstream and downstream processes has the potential to...

The development and validation of a quality by design based process analytical tool for the inline quantification of Ramipril during hot-melt extrusion

09 Jun 2023 | Contributor(s): Dadou, Suha, Senta-Loys, Zoe, Almajaan, Ammar, Li, Shu, Jones, David, Healy, Anne, Tian, Yiwei, Andrews, Gavin

Continuous processing is superseding conventional batch processing as a means of manufacturing within the pharmaceutical Research Article/industry. This paradigm shift has led to the implementation of Process Analytical Technology (PAT) as a semi-automatic, predictive tool offering real-time...

Systematic development of a high dosage formulation to enable direct compression of a poorly flowing API: A case study

09 Jun 2023 | Contributor(s): Schaller, BE, Moroney, KM, Castro-Dominguez, B, Cronin, P, Belen-Girona, J, Ruane, P, Croker, DM, Walker, GM

In this work, the transfer of oral solid dosage forms, currently manufactured via wet granulation, to a continuous direct compression process was considered. Two main challenges were addressed: (1) a poorly flowing API (Canagliflozin) and (2) high drug loading (51 wt%). A scientific approach was...

Systematic Framework for Design and Adaption of Fast, Flexible, Continuous Modular Plants

09 Jun 2023 | Contributor(s): Singh, Ravendra, Gernaey, Krist Gani, Rafiqul, Woodley, John

Not available

Systematic framework for implementation of material traceability into continuous pharmaceutical tablet manufacturing process

09 Jun 2023 | Contributor(s): Billups, Matthew, Singh, Ravendra

Purpose: With the applications of more advanced manufacturing technologies being applied to the pharmaceutical industry, continuous processes are at the forefront of innovation. One area that is highly desired to be systematically investigated is material traceability in continuous manufacturing...