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A Continuous Process for Manufacturing Apremilast. Part I: Process Development and Intensification by Utilizing Flow Chemistry Principles
24 Apr 2024 | Contributor(s):: Hsieh, Hsiao-Wu, Griffin, Daniel J., Ananthoji, Padmini, Avci, Nadide Hazal, Brown, Derek B., Ericson, Ari, Fostinis, James D., Irfan, Muhammad, Langille, Neil, Lovette, Michael A., Murray, James I., Spada, Simone, Thiel, Oliver R., Aiello, Frankie, Daou, Joseph, Goudas-Salomon, Nicole, Pan, Ende, Sarkar, Nandini, Wimalasinghe, Rasangi, Wu, Zufan Steven, Zeng, Alicia, Beaver, Matthew G., Cohen, Carolyn M.
Herein, we report the development of an integrated continuous manufacturing (CM) process for the penultimate step in the synthesis of apremilast, the drug substance (DS) of the commercial product Otezla. This development effort was motivated by the desire to create an alternative manufacturing...
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Using PAT to accelerate the transition to continuous API manufacturing
09 Jun 2023 | Contributor(s):: Gouveia, Francisca, Rahbek, Jesper, Mortensen, Asmus, Pedersen, Mette, Felizardo, Pedro, Bro, Rasmus, Mealy, Michael
Significant improvements can be realized by converting conventional batch processes into continuous ones. The main drivers include reduction of cost and waste, increased safety, and simpler scale-up and tech transfer activities. Redesigning the process layout offers the opportunity to incorporate...
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Scaling continuous API synthesis from milligram to kilogram: extending the enabling benefits of micro to the plant
09 Jun 2023 | Contributor(s):: Berton, M, de, Souza, JMAbdiaj, I, McQuade, DT, Snead, DR
The signature benefits of continuous flow are largely a result of a reactor's micro-sized features. However, as the technology gains industrial traction in the synthesis of active pharmaceutical ingredients (API), the reactors must be scaled to larger size to meet production demands. Often, the...
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Predicting feeder performance based on material flow properties
09 Jun 2023 | Contributor(s):: Yifan Wang, Benjamin J. Glasser, Fernando J. Muzzio
Purpose: Accurate and consistent delivery of materials by well-designed feeders ensures overall process stability. Importantly, feeding performance is strongly dependent on material flow properties. The purpose of this study is to develop a methodology that identifies predictive correlation...
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Identifying a Loss-in-Weight Feeder Design Space Based on Performance and Material Properties
09 Jun 2023 | Contributor(s):: Li, Tianyi, Scicolone, James V. Sanchez, Eric, Muzzio, Fernando J.
Powder properties, such as density and adhesion, can cause large variability in the flow rate of ingredients fed from feeders, which can propagate through the system. Knowing an ideal range of operation and correlating powder properties to process performance can result in faster optimization of...
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Fine grade engineered microcrystalline cellulose excipients for direct compaction: Assessing suitability of different dry coating processes
09 Jun 2023 | Contributor(s):: Chen, Liang, He, Zizhou, Kunnath, Kuriakose, Zheng, Kai, Kim, Sangah, Dave, Rajesh N.
Recent work showed that contrary to conventional wisdom, fine surface engineered excipients outperform their larger counterparts in blends of highly loaded blends of cohesive drug powders in terms of their packing, flowability and tablet tensile strength. Here, two continuous devices, fluid...
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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...
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Characterization of Amorphous Solid Dispersion of Pharmaceutical Compound with pH-Dependent Solubility Prepared by Continuous-Spray Granulator
09 Jun 2023 | Contributor(s):: Tanaka, R, Hattori, YHorie, Y, Kamada, H, Nagato, T, Otsuka, M
A continuous-spray granulator (CTS-SGR) is a one-step granulation technology capable of using solutions or suspensions. The present Research Article objectives were, (1) to reduce the manufacturing operations for solid dosage formulations, (2) to make amorphous solid dispersion (ASD) granules...
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Bachem - Insights into Peptide Chemistry Achievements by the World's Leading Independent Manufacturer of Peptides
09 Jun 2023 | Contributor(s):: Mergler, M, Loidl, GDiekmann, M, Dick, F
The Swiss fine chemicals company Bachem, pioneer and specialist in the chemical synthesis of peptides, has also become an internationally leading manufacturer of peptide active pharmaceutical ingredients (APIs). In response to increasing demands in scale and purity, Bachem's Research Article...