-
The route from problem to solution in multistep continuous flow synthesis of pharmaceutical compounds
Contributor(s):: Bana, P, Orkenyi, RLovei, K, Lako, A, Turos, GI, Eles, J, Faigl, F, Greiner, I
Recent advances in the field of continuous flow chemistry allow the multistep preparation of complex molecules such as APIs (Active Pharmaceutical Ingredients) in a telescoped manner. Numerous examples of laboratory-scale applications are described, which are pointing towards novel manufacturing...
-
The Evolving State of Continuous Processing in Pharmaceutical API Manufacturing: A Survey of Pharmaceutical Companies and Contract Manufacturing Organizations
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...
-
Tailoring the crystal size distribution of an active pharmaceutical ingredient by continuous antisolvent crystallization in a planar oscillatory flow crystallizer
Contributor(s):: Cruz, P, Alvarez, CRocha, F, Ferreira, A
An active pharmaceutical ingredient is currently produced in a traditional batch antisolvent crystallization process. Although well-established, this process lacks flexibility to control the crystal size distribution (CSD). Therefore, a new process was developed to enable the control of the CSD...
-
Improving Feedability of Highly Adhesive Active Pharmaceutical Ingredients by Silication
Contributor(s):: Escotet-Espinoza, M. Sebastian, Moghtadernejad, Sara, Sanchez, Eric, Cappuyns, Philippe, Van Assche, Ivo, Di Pretoro, Giustino, Ierapetritou, Marianthi, Scicolone, James V., Muzzio, Fernando J.
Purpose: Loss-in-weight feeders play a vital role in assuring blend and content uniformity as well as lot-to-lot powder traceability in continuous manufacturing. Irregular flow from the feeders propagates through the system, potentially resulting in out-of-specification product. Powder properties...
-
Continuous flow technology vs. the batch-by-batch approach to produce pharmaceutical compounds
Contributor(s):: Cole, KP, Johnson, MD
Introduction: For the manufacture of small molecule drugs, many pharmaceutical innovator companies have recently invested in continuous processing, which can offer significant technical and economic advantages over traditional batch methodology. This Expert Review will describe the reasons for...
-
Catalytic hydrogenation of N-4-nitrophenyl nicotinamide in a micro-packed bed reactor
Contributor(s):: Yang, CX, Teixeira, ARShi, YX, Born, SC, Lin, HK, Song, YFL, Martin, B, Schenkel, B, Lachegurabi, MP, Jensen, KF
Recent advancements in micro-flow technologies and a drive toward more efficient, greener and safer processes have led to a renaissance in flow-chemistry for pharmaceutical production. In this work, we demonstrate the use of a stabilized Pd nanoparticle-organic-silica catalyst to selectively...
-
Assessing inter- and intramolecular continuous-flow strategies towards methylphenidate (Ritalin) hydrochloride
Contributor(s):: Gerardy, R, Winter, MVizza, A, Monbaliu, JCM
The batch-to-flow translation of inter-and intramolecular strategies for the diastereoselective preparation of the active pharmaceutical ingredient threo-methylphenidate hydrochloride is presented. Both inter-and intramolecular strategies imply the telescoping of multiple processing steps and the...
-
Assessment of blending performance of pharmaceutical powder mixtures in a continuous mixer using Discrete Element Method (DEM)
Contributor(s):: Behjani, MA, Motlagh, YGBayly, AE, Hassanpour, A
This study proposes a new sample-independent mixing index, termed the Coefficient of Blending Performance (CBP), for monitoring the formation of undesired API (Active Pharmaceutical Ingredient) agglomerates in continuous mixing processes. The proposed index is examined for the blending of...
-
Assessment of Robustness for a Near-Infrared Concentration Model for Real-Time Release Testing in a Continuous Manufacturing Process
Contributor(s):: Colon, Yleana, Vargas, Jenny, Sánchez, Eric, Navarro, Gilfredo, Romañach, Rodolfo
This study describes the robustness test of a transmission near-infrared spectroscopic (NIRS) model for prediction of drug concentration in core tablets as part of real-time release testing (RTRt) efforts for a continuous manufacturing process. Seven calibration blend samples were prepared...
-
Active pharmaceutical ingredient (API) production involving continuous processes - A process systems engineering (PSE)-assisted design framework
Contributor(s):: Cervera-Padrell, AE, Skovby, TKiil, S, Gani, R, Gernaey, KV
A systematic framework is proposed for the design of continuous pharmaceutical manufacturing processes. Specifically, the design framework focuses on organic chemistry based, active pharmaceutical ingredient (API) synthetic processes, but could potentially be extended to biocatalytic and...
-
Acceleration of Anti-Markovnikov Hydroamination in the Synthesis of an Active Pharmaceutical Ingredient
Contributor(s):: Mitic, A, Skovby, TDam-Johansen, K, Gernaey, KV
Slow chemical reactions are a big challenge in the modern pharmaceutical industry. Their accelerations together with the introduction of continuous manufacturing modes are major drivers for future development. One example reaction is hydroamination, a reaction between unsaturated hydrocarbons and...