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

09 Jun 2023 | 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 | 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 | 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 | 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 | 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...

Challenges in tracing material flow passing a loss-in-weight feeder in continuous manufacturing processes

09 Jun 2023 | Contributor(s): Peterwitz, Moritz, Gerling, Sina, Schembecker, Gerhard

Loss-in-weight feeders are an integral part of most continuous manufacturing processes, ensuring a constant mass flow. The feeders cause a significant degree of back-mixing in such lines. Understanding back-mixing is essential for the treatment of disturbances. However, feeders refilled...

Challenges, opportunities and recent advances in near infrared spectroscopy applications for monitoring blend uniformity in the continuous manufacturing of solid oral dosage forms

09 Jun 2023 | Contributor(s): Velez, Natasha L., Drennen, James K., Anderson, Carl A.

Near infrared (NIR) spectroscopy has been widely recognized as a powerful PAT tool for monitoring blend uniformity in continuous manufacturing (CM) processes. However, the dynamic nature of the powder stream and the fast rate at which it moves, compared to batch processes, introduces challenges...

Characteristics of multi-component formulation granules formed using distributive mixing elements in twin screw granulation

09 Jun 2023 | Contributor(s): Pradhan, Shankali U., Sen, Maitraye, Li, Jiayu, Gabbott, Ian, Reynolds, Gavin, Litster, James D., Wassgren, Carl R.

This work examines the influence of pharmaceutical powder formulation characteristics on granule properties formed using distributive mixing elements (DMEs) in twin screw granulation. High and low drug dose formulations with three different active pharmaceutical ingredients (APIs) were...

Characteristics of residence time distribution in a continuous high shear mixer granulation using scraper rotation

09 Jun 2023 | Contributor(s): Tomita, Yosuke, Takeuchi, Yoshiko, Natsuyama, Susumu, Takeuchi, Hirofumi

Characteristics of residence time distribution (RTD) in a continuous high shear mixer granulation were investigated to promote the development of a continuous manufacturing process in the pharmaceutical industry. A continuous granulator with an impeller and a scraper was utilized. The tracer...

Characterization and Modeling of the Operating Curves of Membrane Microseparators

09 Jun 2023 | Contributor(s): Yang, L, Weeranoppanant, N, Jensen, KF

The membrane microseparator is a milliliter-scale flow chemistry module that continuously separates a biphasic flow through a PTFE microporous membrane. It has found a wide range of applications in the continuous manufacturing of active pharmaceutical ingredients and fine chemicals, especially...

Characterization of a Modular Continuous Vacuum Screw Filter for Small-Scale Solid-Liquid Separation of Suspensions

09 Jun 2023 | Contributor(s): Steenweg, C, Seifert, AISchembecker, G, Wohlgemuth, K

A key enabler for the future success of continuous manufacturing in pharmaceutical and fine chemical production processes is the control of product quality. Since approx. 90% of all small molecular active pharmaceutical ingredients produced involve a crystallization step, a holistic view on its...

Characterization of a novel hydroxypropyl methylcellulose (HPMC) direct compression grade excipient for pharmaceutical tablets

09 Jun 2023 | Contributor(s): Allenspach, Carl, Timmins, Peter, Sharif, Shasad, Minko, Tamara

Controlled release tablets are important dosage forms enabling a slower release of the drug and better pharmacokinetics for some drugs and hydrophilic matrix tablets utilizing hydroxypropyl methylcellulose (HPMC) are one of the most common types. One of the main challenges with using HPMC is its...

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...

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...

Automated and continuous synthesis of drug substances

09 Jun 2023 | Contributor(s): Sacher, Stephan, Castillo, Ismael, Rehrla, Jakob, Sagmeistera, Peter, Lebl, René, Kruisza, Julia, Celikovic, Selma, Sipek, Martin, Williams, Jason D, Kirschneck, Dirk, Kappea, C. Oliver, Horn, Martin

A continuous synthesis line was developed integrating different common reaction stepsnamely nitration, substitution and hydrogenation. Mesalazine as model drug substancewas produced from 2-chlorobenzoic acid in continuous flow mode. A multi-instrument PATstrategy was implemented to equip the full...

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...

Benchtop NIR method development for continuous manufacturing scale to enable efficient PAT application for solid oral dosage form

09 Jun 2023 | Contributor(s): Alam, MA, Liu, YADolph, S, Pawliczek, M, Peeters, E, Palm, A

A Near Infrared (NIR) method was developed using a small benchtop feed frame system to quantify Saccharin potency in a powder blend during continuous manufacturing process. A 15-point Design of Experiments (DoE) was created based on the NIR spectral response and compositions of the formulation to...

Biocatalytic Continuous Manufacturing of Diabetes Drug: Plantwide Process Modeling, Optimization, and Environmental and Economic Analysis

09 Jun 2023 | Contributor(s): Ho, CH, Yi, JR, Wang, XN

This work proposes a comprehensive framework of biocatalytic continuous manufacturing of sitagliptin, the active pharmaceutical ingredient of the leading dipeptidyl peptidase-4 inhibitor antidiabetic drug. Continuous manufacturing has the advantages of quality consistency, reduced waste...

Biocompatible Alginate Microgel Particles as Heteronucleants and Encapsulating Vehicles for Hydrophilic and Hydrophobic Drugs

09 Jun 2023 | Contributor(s): Eral, HB, Lopez-Mejias, VO'Mahony, M, Trout, BL, Myerson, AS, Doyle, PS

Biocompatible materials that can control crystallization while carrying large amounts of active pharmaceutical ingredients (APIs) with diverse chemical properties are in demand in industrial practice. In this study, we investigate the utility of biocompatible alginate (ALG) hydrogels as a...

Blend Segregation in Tablets Manufacturing and Its Effect on Drug Content Uniformity-A Review

09 Jun 2023 | Contributor(s): Jakubowska, E, Ciepluch, N

Content uniformity (CU) of the active pharmaceutical ingredient is a critical quality attribute of tablets as a dosage form, ensuring reproducible drug potency. Failure to meet the accepted uniformity in the final product may be caused either by suboptimal mixing and insufficient initial blend...

Breakage and drying behaviour of granules in a continuous fluid bed dryer: Influence of process parameters and wet granule transfer

09 Jun 2023 | Contributor(s): De Leersnyder, F., Vanhoorne, V., Bekaert, H., Vercruysse, J., Ghijs, M., Bostijn, N., Verstraeten, M., Cappuyns, P., Van Assche, I., Vander Heyden, Y., Ziemons, E., Remon, J. P., Nopens, I., Vervaet, C., De Beer, T.

Although twin screw granulation has already been widely studied in recent years, only few studies addressed the subsequent continuous drying which is required after wet granulation and still suffers from a lack of detailed understanding. The latter is important for optimisation and control and,...

Breaking Through Barriers to Continuous Manufacturing

09 Jun 2023 | Contributor(s): Markarian, Jennifer

Pharmaceutical manufacturing is inching towards implementing more efficient and sustainable processes, including continuous manufacturing (CM) of solid-dosage drugs. Advantages of CM include the potential for faster development, easier technical transfer, and more efficient and flexible...

Catalytic hydrogenation of N-4-nitrophenyl nicotinamide in a micro-packed bed reactor

09 Jun 2023 | 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...