Characterization of material properties

09 Jun 2023 | Contributor(s): Razavi, Sonia, Oka, Sarang, Escotet-Espinoza, M. Sebastian, Wang, Yifan, Li, Tianyi, Futran Mauricio., Muzzio, Fernando

This chapter describes the importance of deepening our understanding of material properties and their effect on process performance. There are many measurement techniques to describe the complex nature of powders, some of which are provided in this chapter. Strong knowledge of multivariate...

Characterization of Near-Infrared and Raman Spectroscopy for In-Line Monitoring of a Low-Drug Load Formulation in a Continuous Manufacturing Process

09 Jun 2023 | Contributor(s): Harms, Zachary, Shi, Zhenqi: Kulkarni, Rajesh, Myers, David P.

Reflectance spectroscopy is an excellent candidate for process analytical technology (PAT) applications in continuous manufacturing of pharmaceutical tablets. Spectroscopic methods provide a real-time, nondestructive measurement of the active pharmaceutical ingredient (API) concentration in order...

Characterization of NIR interfaces for the feeding and in-line monitoring of a continuous granulation process

09 Jun 2023 | Contributor(s): Román-Ospino, Andrés D, Tamrakar, Ashutosh Igne, Benoît Dimaso, Elyse Towns Airiau, Christian Clancy, Donald J Pereira, Glinka Muzzio, Fernando J Singh, Ravendra, Ramachandran, Rohit

This work describes the characterization of three NIR interfaces intended to monitor a continuous granulation process. Two interfaces (i.e. a barrel interface and a rotating paddle interface) were evaluated to monitor the API concentration at the entrance of the granulator, and a third interface...

Characterizing drug product continuous manufacturing residence time distributions of major/minor excipient step changes using near infrared spectroscopy and process parameters

09 Jun 2023 | Contributor(s): Shi, Zhenqi, Manley, Leo

The material residence time distribution in a continuous manufacturing process can be utilized to develop, design and justify the process control strategy. This paper successfully demonstrates using both major and minor formulation component step changes to determine the system response using...

Chemoenzymatic Synthesis in Flow Reactors: A Rapid and Convenient Preparation of Captopril

10 May 2024 | Contributor(s): De Vitis, Valerio, Dall'Oglio, Federica, Pinto, Andrea, De Micheli, Carlo, Molinari, Francesco, Conti, Paola, Romano, Diego, Tamborini, Lucia

The chemoenzymatic flow synthesis of enantiomerically pure captopril, a widely used antihypertensive drug, is accomplished starting from simple, inexpensive, and readily available reagents. The first step is a heterogeneous biocatalyzed regio- and stereoselective oxidation of cheap prochiral...

Cleaning of direct compression continuous manufacturing equipment through displacement of API residues by excipients

23 Jul 2024 | Contributor(s): Patel, Dhavalkumar S, Méndez, Rafael, Romañach, Rodolfo J

This feasibility study evaluates a cleaning process designed to avoid the use of detergents and reduce operator exposure to the active pharmaceutical ingredient (API). The continuous manufacturing equipment was cleaned using excipients to displace ibuprofen residues from the system. The cleaning...

Closed-loop feedback control of a continuous pharmaceutical tablet manufacturing process via wet granulation

09 Jun 2023 | Contributor(s): Singh, Ravendra, Barrasso, Dana Chaudhury, Anwesha Sen, Maitraye Ierapetritou, Marianthi Ramachandran, Rohit

The wet granulation route of tablet manufacturing in a pharmaceutical manufacturing process is very common due to its numerous processing advantages such as enhanced powder flow and decreased segregation. However, this route is still operated in batch mode with little (if any) usage of an...

Co-crystals of diflunisal and isomeric pyridinecarboxamides - a thermodynamics and crystal engineering contribution

09 Jun 2023 | Contributor(s): Evora, AOL, Castro, RAEMaria, TMR, Silva, MR, ter, Horst, JH, Canotilho, J, Eusebio, MES

Diflunisal is an anti-inflammatory, non-steroidal drug, class II of the Biopharmaceutical Classification System, which has recently been the subject of renewed interest due to its potential for use in the oral therapy of familial amyloid polyneuropathy. In this study, a thermodynamics based...

Combination of PAT and mechanistic modeling tools in a fully continuous powder to granule line: Rapid and deep process understanding

09 Jun 2023 | Contributor(s): Domokos, András, Pusztai, Éva, Madarász, Lajos, Nagy, Brigitta, Gyürkés, Martin, Farkas, Attila (24372641300), Fülöp, Gergő, Casian, Tibor, Szilágyi, Botond., Nagy, Zsombor Kristóf

Comprehensive understanding of an integrated continuous pharmaceutical technology was achieved in this study by a combining design of experiments and mechanistic modeling-based simulations. The powder to granule line consisted of twin-screw wet granulation, vibrational fluid-bed drying and...

Combined feedforward/feedback control of an integrated continuous granulation process

09 Jun 2023 | Contributor(s): Pereira, Glinka Cathy, Muddu, Shashank Venkat Román-Ospino, Andrés David Clancy, Don Igne, Benoit Airiau, Christian Muzzio, Fernando J Ierapetritou, Marianthi Ramachandran, Rohit, Singh, Ravendra

Continuous manufacturing offers shorter processing times and increased product quality assurance, among several other advantages. This makes it an ever-growing interest among pharmaceutical companies. A suitable efficient control system is however desired for continuous pharmaceutical...

Compact NMR Spectroscopy for Automated Continuous-Flow Production of Chemicals and Pharmaceuticals (On-Demand)

31 Jan 2024 | Seminars | Contributor(s): Klas Meyer

Chemical companies are under constant pressure to improve productivity while cutting costs. Flexible and modular chemical plants can produce high-quality products using multi-purpose equipment with short downtimes, reducing time to market for new products. Intensified continuous production...

Compaction properties of melt coated coarse drug particles

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Gren, T, Nystrom, C

Xylitol and stearic acid were applied onto the surfaces of coarse particles of paracetamol and acetylsalicylic acid by continuous multipurpose melt technology. The effect of melt coating on radial and axial tensile strength was studied and compared to that of dry mixing of paracetamol and...

Comparative investigation of supersaturation and automated direct nucleation control of crystal size distributions using ATR-UV/vis spectroscopy and FBRM

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Saleemi, Ali N., Rielly, Chris D., Nagy, Zoltan K.

The paper presents a thorough evaluation of different control strategies used in cooling crystallization, namely, unseeded linear cooling, seeded linear cooling, supersaturation control, and automated direct nucleation control. The sensitivity and robustness of supersaturation and automated...

Comparative performance of concentration and temperature controlled batch crystallizations

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Nagy, Zoltan K., Chew, Jia W. Fujiwara, Mitsuko, Braatz, Richard D.

An increased interest has been directed towards the crystallization of pharmaceuticals and proteins in recent years, which have additional complications compared to the extensively studied inorganic batch and continuous crystallizations. Recent advances in process analytical technology have...

Comparative Study of a Novel Micro-feeder and Loss-in-weight Feeders

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sacher, S, Fathollahi, S, Khinast, JG

Purpose Accurate and reliable feeding of small quantities of powder is crucial in many industries. It is particularly true in the case of pharmaceutical manufacturing. First, the exact dosage of highly potent active pharmaceutical ingredients (APIs) is essential. Second, due to the shift towards...

Comparison between integrated continuous direct compression line and batch processing - The effect of raw material properties

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Karttunen, AP, Wikstrom, HTajarobi, P, Fransson, M, Sparen, A, Marucci, M, Ketolainen, J, Folestad, S, Korhonen, O, Abrahmsen-Alami, S

There is a current trend in pharmaceutical manufacturing to shift from traditional batch manufacture to continuous manufacturing. The purpose of this study was to test the ability of an integrated continuous direct compression (CDC) line, in relation to batch processing, to achieve consistent...

Comparison Between Pure Component Modeling Approaches for Monitoring Pharmaceutical Powder Blends with Near‑Infrared Spectroscopy in Continuous Manufacturing Schemes

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Rish, Adam J., Henson, Samuel R., Alam, Md. Anik, Liu, Yang, Drennen, James K., Anderson, Carl A.

Near-infrared (NIR) spectroscopy has become an important process analytical technology (PAT) for monitoring and implementing control in continuous manufacturing (CM) schemes. However, NIR requires complex multivariate models to properly extract the relevant information and the traditional model...

Comparison of a Batch and Flow Approach for the Lipase-Catalyzed Resolution of a Cyclopropanecarboxylate Ester, A Key Building Block for the Synthesis of Ticagrelor

25 Jun 2024 | Peer-reviewed journal | Contributor(s): Hugentobler, Katharina G., Rasparini, Marcello, Thompson, Lisa A., Jolley, Katherine E., Blacker, A. John, Turner, Nicholas J.

In this study a batch reactor process is compared to a flow chemistry approach for lipase-catalyzed resolution of the cyclopropanecarboxylate ester (±)-3. (1R,2R)-3 is a precursor of the amine (1R,2S)-2 which is a key building block of the API ticagrelor. For both flow and batch operation, the...

Comparison of a continuous ring layer wet granulation process with batch high shear and fluidized bed granulation processes

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Jarvinen, MA, Paavola, M, Poutiainen, S, Itkonen, P, Pasanen, V, Uljas, K, Leiviska, K, Juuti, M, Ketolainen, J, Jarvinen, K

The traditional batch wet granulation processes encounter several challenges, such as problems in the scale-up step, batch-to-batch variability together with the multivariate and difficult to control nature of the process. A continuous wet granulation technique could be a possible solution for...

Complexation-Assisted Continuous Crystallization of Isomeric Systems with Nanofiltration Recycle

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Vartak, S, Myerson, AS

In API-impurity systems consisting of structural isomers, the impurity has a strong affinity to incorporate into the host crystal owing to their identical molecular weight and similar structure. Conventional successive recrystallization turns out to be an unattractive purification strategy in...

Composite Hydrogels Laden with Crystalline Active Pharmaceutical Ingredients of Controlled Size and Loading

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Eral, HB, O'Mahony, MShaw, R, Trout, BL, Myerson, AS, Doyle, PS

Efficient control of crystallization and crystal properties still represents a bottleneck in the manufacturing of crystalline materials ranging from pigments to semiconductor particles. In the case of pharmaceutical drug manufacture, current methods for controlling critical crystal properties...

Comprehensive modelling of pharmaceutical solvation energy in different solvents

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Panwar, A, Shirazian, SSingh, M, Walker, GM

Crystallization is an important processing step in production of active pharmaceutical ingredients (API). This process is used to recover/separate the synthesized APIs for further processing to final solid dosage oral formulations. Control and understanding of crystallization are of great...

Computer Aided Design of Solvent Blends for Hybrid Cooling and Antisolvent Crystallization of Active Pharmaceutical Ingredients

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Watson, OL, Jonuzaj, SMcGinty, J, Sefcik, J, Galindo, A, Jackson, G, Adjiman, CS

Choosing a solvent and an antisolvent for a new crystallization process is challenging due to the sheer number of possible solvent mixtures and the impact of solvent composition and crystallization temperature on process performance. To facilitate this choice, we present a general computer aided...

Concentration monitoring with near infrared chemical imaging in a tableting press

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Dalvi, Himmat, Fauteux-Lefebvre, Clémence, Guay, Jean-Maxime, Abatzoglou, Nicolas, Gosselin, Ryan

Monitoring powder potency and homogeneity is important in achieving real-time release testing in a continuous tablet manufacturing operation. If quality related issues are encountered, monitoring powder potency inside a feed frame offers a last opportunity to intervene in the process before...

Conceptual framework for model-based analysis of residence time distribution in twin-screw granulation

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Kumar, Ashish, Vercruysse, Jurgen, Vanhoorne, Valerie, Toiviainen, Maunu, Panouillot, Pierre-Emmanuel, Juuti, Mikko, Vervaet, Chris, Remon, Jean Paul, Gernaey, Krist V., De Beer, Thomas, Nopens, Ingmar

Twin-screw granulation is a promising continuous alternative for traditional batchwise wet granulation processes. The twin-screw granulator (TSG) screws consist of transport and kneading element modules. Therefore, the granulation to a large extent is governed by the residence time distribution...