Continuous, one-step synthesis of pharmaceutical cocrystals via hot melt extrusion from neat to matrix-assisted processing - State of the art

09 Jun 2023 | Contributor(s): Gajda, Maciej, Nartowski, Karol P., Pluta, Janusz, Karolewicz, Bożena

Use of hot melt extrusion (HME) as continuous manufacturing process in the cocrystal synthesis is of increasing interest from both industrial and academic perspective and it is seen as a newly developing branch of mechanochemistry with possible broad application in single step synthesis and...

Continuous-Flow Technology—A Tool for the Safe Manufacturing of Active Pharmaceutical Ingredients

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

In the past few years, continuous-flow reactors with channel dimensions in the micro- or millimeter region have found widespread application in organic synthesis. The characteristic properties of these reactors are their exceptionally fast heat and mass transfer. In microstructured devices of...

Continuous-flow tubular crystallization in slugs spontaneously induced by hydrodynamics

09 Jun 2023 | Contributor(s): Jiang, Mo, Zhu, Zhilong Jimenez, Ernesto Papageorgiou, Charles D., Waetzig, Josh, Hardy, Andrew, Langston, Marianne, Braatz, Richard D.

A novel continuous crystallizer design is described with the potential to provide improved control of crystal properties, improved process reproducibility, and reduced scale-up risk. Liquid and gas are introduced into one end of the tube at flow rates selected to spontaneously generate...

Continuous purification of active pharmaceutical ingredients using multistage organic solvent nanofiltration membrane cascade

09 Jun 2023 | Contributor(s): Peeva, L, Burgal, JDValtcheva, I, Livingston, AG

Downstream processing accounts for a large fraction of the production costs in pharmaceutical manufacturing. Organic solvent nanofiltration performed in a membrane cascade offers an interesting possibility for a continuous downstream processing unit operation. This work demonstrates continuous...

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...

Continuous reactive crystallization of an API in PFR-CSTR cascade with in-line PATs

09 Jun 2023 | Contributor(s): Hu, CT, Shores, BTDerech, RA, Testa, CJ, Hermant, P, Wu, W, Shvedova, K, Ramnath, A, Al, Ismaili, LQ, Su, QL, Sayin, R, Born, SC, Takizawa, B, O'Connor, TF, Yang, XC, Ramanujam, S, Mascia, S

The continuous reactive crystallization of an active pharmaceutical ingredient (API) in a plug flow reactor (PFR)-continuous stirred tank reactor (CSTR) cascade system with in-line PATs was developed and investigated. Residence time distribution (RTD) measurements of the PFR (stage 1), the CSTR...

Continuous Single-Step Wet Granulation with Integrated in-Barrel-Drying

09 Jun 2023 | Contributor(s): Schmidt, Adrian, de Waard, Hans, Kleinebudde, Peter, Krumme, Markus

Purpose It was investigated if continuous wet granulation and drying could be combined in a twin-screw granulator with the aimto provide (pre-) dried granules in a single-step process, i.e. in-barrel-drying. Methods To have a consistent and robust material propulsionmechanism, a twin-screw...

Continuous twin screw extrusion for the wet granulation of lactose

09 Jun 2023 | Contributor(s): Keleb, EI, Vermeire, A, Vervaet, C, Remon, JP

The Suitability of continuous twin screw extrusion for the wet granulation of a-lactose monohydrate was studied and compared with conventional high shear granulation. The influence of process parameters (screw speed and total input rate) and formulation variables (water and polyvinylpyrrolidone...

Continuous twin screw granulation - An advanced alternative granulation technology for use in the pharmaceutical industry

09 Jun 2023 | Contributor(s): Bandari, Suresh, Nyavanandi, Dinesh, Kallakunta, Venkata Raman, Janga, Kartik Yadav, Sarabu, Sandeep, Butreddy, Arun, Repka, Michael A.

Hot melt extrusion has been an exciting technology in the pharmaceutical field owing to its novel applicability. Twin-screw granulation presents a great potential and offers many advantages relative to conventional granulation processes. Different twin-screw granulation techniques, such as...

Continuous twin screw granulation and fluid bed drying: A mechanistic scaling approach focusing optimal tablet properties

09 Jun 2023 | Contributor(s): Menth, Judith, Maus, Martin, Wagner, Karl G.

This study provides the results of investigation on scaling approaches for three differently-sized continuous granulation lines, each consisting of a twin screw wet granulation process and a continuous fluid bed drying process. To check the initial scaling approach with regard to granule and...

Continuous twin screw granulation: A complex interplay between formulation properties, process settings and screw design

09 Jun 2023 | Contributor(s): Portier, Christoph, Pandelaere, KDelaet, U, Vigh, T, Di, Pretoro, G, De, Beer, T, Vervaet, C, Vanhoorne, V

Due to the numerous advantages over batch manufacturing, continuous manufacturing techniques such as twin screw wet granulation are rapidly gaining importance in pharmaceutical production. Since a large knowledge gap on the importance of formulation variables exists, this study systematically...

Continuous Twin Screw Granulation: A Review of Recent Progress and Opportunities in Formulation and Equipment Design

09 Jun 2023 | Contributor(s): Portier, Christoph, Vervaet, Chris, Vanhoorne, Valérie

Continuous twin screw wet granulation is one of the key continuous manufacturing technologies that have gained significant interest in the pharmaceutical industry as well as in academia over the last ten years. Given its considerable advantages compared to wet granulation techniques operated in...

Continuous manufacturing: A changing processing paradigm

09 Jun 2023 | Contributor(s): Randi Hernandez

Continuous manufacturing: the future in pharmaceutical solid dosage form manufacturing

09 Jun 2023 | Contributor(s): Desai, Parind Mahendrakumar, Van Vaerenbergh, Griet, Holman, Jim, Liew, Celine Valeria, Heng, Paul Wan Sia

As rising costs outpace new drug development, the pharmaceutical industry has come under intense pressure to improve the efficiency of its manufacturing processes. Continuous process manufacturing provides a proven solution. Among its many benefits are: minimized waste, energy consumption, and...

Continuous manufacturing via hot-melt extrusion and scale up: regulatory matters

09 Jun 2023 | Contributor(s): Mohammed Maniruzzaman, Ali Nokhodchi

Over recent decades, HME techniques have appeared as an innovative manufacturing platform for various pharmaceutical applications. HME has been successfully applied to develop multiple drug delivery systems for various applications (e.g., solubility enhancement, sustained release, taste masking,...

Continuous Melt Granulation for Taste-Masking of Ibuprofen

09 Jun 2023 | Contributor(s): Forster, Seth P., Lebo, David B.

This book covers key aspects of the continuous manufacturing of pharmaceuticals. The first part provides an overview of key chemical engineering principles and the current regulatory environment. The second covers existing technologies for manufacturing both small-molecule-based products and...

Continuous mixing of powder mixtures with pharmaceutical process constraints

09 Jun 2023 | Contributor(s): Berthiaux, H, Marikh, K, Gatumel, C

While it would provide many advantages from many aspects, the application of continuous mixing processes to the pharmaceutical field is still in its infancy. In this paper we report results concerning the continuous mixing of nine ingredients (including three actives) that constitute a current...

Continuous Pharmaceutical Crystallization from Solution

09 Jun 2023 | Contributor(s): Price, CJ

Brings together the essential know-how for anyone working in drug manufacturing, as well as chemical, food, and pharmaceutical scientists working on continuous processing

Continuous Pharmaceutical Processing

09 Jun 2023 | Contributor(s): Zoltan K Nagy, Arwa El Hagrasy, Jim Litster

Covers chemical engineering principles, regulatory aspects, primary and secondary manufacturing, process analytical technology and quality-by-design

Continuous plug flow crystallization of pharmaceutical compounds

09 Jun 2023 | Contributor(s): Alvarez, Alejandro J., Myerson, Allan S.

Contains contributions from researchers in leading pharmaceutical companies, the FDA, and academic institutions

Continuous powder feeding for pharmaceutical solid dosage form manufacture: a short review

09 Jun 2023 | Contributor(s): Blackshields, Caroline A., Crean, Abina M.

Offers an extremely well-informed look at the most promising future approaches to continuous manufacturing of innovative pharmaceutical products

Continuous processing and the applications of online tools in pharmaceutical product manufacture: developments and examples

09 Jun 2023 | Contributor(s): Ooi, Shing Minga, Sarkar, Srimantaa, Van Varenbergh, Grietb, Schoeters, Krisb, Heng, Paul Wan Sia

Continuous processing and production in pharmaceutical manufacturing has received increased attention in recent years mainly due to the industries’ pressing needs for more efficient, cost-effective processes and production, as well as regulatory facilitation. To achieve optimum product quality,...

Continuous Processing in the Manufacture of Active Pharmaceutical Ingredients and Finished Dosage Forms: An Industry Perspective

09 Jun 2023 | Contributor(s): Poechlauer, P, Manley, JBroxterman, R, Gregertsen, B, Ridemark, M

Continuous manufacturing as a way of producing fine chemicals, active pharmaceutical ingredients, and finished dosage forms is gaining widespread attention. Although potential benefits over traditional batch-wise production have been discussed at many occasions and appear evident, continuous...

Continuous Processing of Active Pharmaceutical Ingredients Suspensions via Dynamic Cross-Flow Filtration

09 Jun 2023 | Contributor(s): Gursch, J, Hohl, RToschkoff, G, Dujmovic, D, Brozio, J, Krumme, M, Rasenack, N, Khinast, J

Over the last years, continuous manufacturing has created significant interest in the pharmaceutical industry. Continuous filtration at low flow rates and high solid loadings poses, however, a significant challenge. A commercially available, continuously operating, dynamic cross-flow filtration...

Continuous Production of Five Active Pharmaceutical Ingredients in Flexible Plug-and-Play Modules: A Demonstration Campaign

09 Jun 2023 | Contributor(s): Rogers, L, Briggs, NAchermann, R, Adamo, A, Azad, M, Brancazio, D, Capellades, G, Hammersmith, G, Hart, T, Imbrogno, J, Kelly, LP, Liang, GH, Neurohr, C, Rapp, K, Russell, MG, Salz, C, Thomas, DA, Weimann, L, Jamison, TF, Myerson, AS, Jensen, KF

Traditional pharmaceutical manufacturing is based on a complex supply chain that is vulnerable to spikes in demand and interruptions. Continuous pharmaceutical production in compact modules is a potential solution that allows for drug manufacturing when and where it is needed with significantly...