In-Line Quantification of Drug and Excipients in Cohesive Powder Blends by near Infrared Spectroscopy

09 Jun 2023 | Contributor(s): Liew, C. V., Karande, A. D., Heng, P. W. S

This work was aimed at investigating the utility of near infrared (NIR) spectroscopy for simultaneous in-line quantification of drug and excipients in cohesive powder blends in a bin blender. A model formulation containing micronized chlorpheniramine maleate (μCPM), lactose, microcrystalline...

In-line Raman spectroscopic monitoring and feedback control of a continuous twin-screw pharmaceutical powder blending and tableting process

09 Jun 2023 | Contributor(s): Nagy, Brigitta, Farkas, Attila, Gyurkes, Martin, Komaromy-Hiller, Szofia, Demuth, Balazs, Szabo, Bence, Nusser, David, Borbas, Eniko, Marosi, Gyorgy, Nagy, Zsombor Kristof

The integration of Process Analytical Technology (PAT) initiative into the continuous production of pharmaceuticals is indispensable for reliable production. The present paper reports the implementation of in-line Raman spectroscopy in a continuous blending and tableting process of a...

Inline UV/Vis spectroscopy as PAT tool for hot-melt extrusion

09 Jun 2023 | Contributor(s): Wesholowski, Jens, Prill, Sebastian, Berghaus, Andreas, Thommes, Markus

Hot-melt extrusion on co-rotating twin screw extruders is a focused technology for the production of pharmaceuticals in the context of Quality by Design. Since it is a continuous process, the potential for minimizing product quality fluctuation is enhanced. A typical application of hot-melt...

In-line UV-Vis Spectroscopy as a Fast-Working Process Analytical Technology (PAT) during Early Phase Product Development Using Hot Melt Extrusion (HME)

09 Jun 2023 | Contributor(s): Schlindwein, Walkiria, Bezerra, Mariana, Almeida, Juan, Berghaus, Andreas, Owen, Martin, Muirhead, Gordon

This paper displays the potential of an in-line PAT system for early phase product development during pharmaceutical continuous manufacturing following a Quality by Design (QbD) framework. Hot melt extrusion (HME) is used as continuous manufacturing process and UV–Vis spectroscopy as an in-line...

Industrial applications of immobilized enzymes-A review

09 Jun 2023 | Contributor(s): Basso, A, Serban, S

The use of immobilized enzymes is now a routine process for the manufacture of many industrial products in the pharmaceutical, chemical and food industry. Some enzymes, such as lipases, are naturally robust and efficient, can be used for the production of many different molecules and have a wide...

Industrial-Scale Continuous Vacuum Drying of Active Pharmaceutical Ingredient Paste: Determination of the Process Window

09 Jun 2023 | Contributor(s): Aigner, I, Zettl, MSchroettner, H, van, der, Wel, P, Khinast, JG, Krumme, M

Many efforts have been made in recent years to adopt and implement continuous processing into the pharmaceutical production chain, driven by the desire to optimize the process efficacy and cost as well as the product quality. In the current challenging times, the need for fast adaptable processes...

Industry perspective on process analytical technology tools and applications in API development

09 Jun 2023 | Contributor(s): Chanda, Arani, Daly, Adrian M., Foley, David A., Lapack, Mark A., Mukherjee, Samrat, Orr, John D., Reid, George L., Thompson, Duncan R., Ward, Howard W.

The IQ Consortium reports on the current state of process analytical technology (PAT) for active pharmaceutical ingredient (API) development in branded pharmaceutical companies. The article uses an API process workflow (process steps from raw material identification through to finished API) to...

Influence of binder attributes on binder effectiveness in a continuous twin screw wet granulation process via wet and dry binder addition

09 Jun 2023 | Contributor(s): Vandevivere, L., Denduyver, P., Portier, C., Hausler, O., De Beer, T., Vervaet, C., Vanhoorne, V.

The effect of a wide variety of binders on the quality of granules produced via continuous twin screw wet granulation was studied. Anhydrous dicalcium phosphate was used as poorly soluble filler and was granulated applying dry or wet addition of binders. Furthermore, dry and wet binder...

Influence of filler selection on twin screw foam granulation

09 Jun 2023 | Contributor(s): Rocca, K. E., Weatherley, S., Sheskey, P. J., Thompson, M. R.

The influence of filler selection in wet granulation was studied for the novel case where the binder is delivered as an unstable, semi-rigid aqueous foam to an extrusion process. The work primarily examined the impact of differing concentrations of microcrystalline cellulose (Avicel PH (R) 101)...

Influence of granulation temperature on particle size distribution of granules in twin-screw granulation (TSG)

09 Jun 2023 | Contributor(s): Ito, Akihiko, Kleinebudde, Peter

This study investigated an influence of granulation temperature during twin-screw granulation (TSG) on particle size distributions (PSDs). The influence of the granulation temperature on granule size distributions varied, depending on the liquid to solid (L/S) ratio, the kind of binders, the...

Influence of material properties and equipment configuration on loss-in-weight feeder performance for drug product continuous manufacture

09 Jun 2023 | Contributor(s): Yadav, IK, Holman, JMeehan, E, Tahir, F, Khoo, J, Taylor, J, Benedetti, A, Aderinto, O, Bajwa, G

A programme of work on continuous tablet manufacturing was completed as part of a UK based collaborative Research Article project (REMEDIES: RE-configuring MEDIcines End-to-end Supply) to evaluate the operating space of the continuous platform with respect to material properties. Loss-in-weight...

Influence of process parameters and equipment on dry foam formulation properties using indomethacin as model drug

09 Jun 2023 | Contributor(s): Sprunk, A, Page, S, Kleinebudde, P

Dry foam technology was developed to overcome insufficient oral bioavailability of poorly soluble and wettable active pharmaceutical ingredients (APIs). It is intended to enable a faster and more efficient dissolution by avoiding API agglomeration and floating of non-wetted API particles. The aim...

Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets

09 Jun 2023 | Contributor(s): Fonteyne, Margot, Wickström, Henrika, Peeters, Elisabeth, Vercruysse, Jurgen, Ehlers, Henrik, Peters, Björn-Hendrik, Remon, Jean Paul, Vervaet, Chris, Ketolainen, Jarkko, Sandler, Niklas, Rantanen, Jukka., Naelapää, Kaisa

Continuous manufacturing gains more and more interest within the pharmaceutical industry. The International Conference of Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product...

Inline Determination of Residence Time distributionin Hot-Melt-Extrusion

09 Jun 2023 | Contributor(s): Wesholowski, Jens, Berghaus, Andreas, Thommes, Markus

In the framework of Quality-by-Design (QbD), the inline determination of process parameters or quality attributes of a product using sufficient process analytical technology (PAT) is a center piece for the establishment of continuous processes as a standard pharmaceutical technology. In this...

Implementing Feedback Granule Size Control in a Continuous DryGranulation Line Using Controlled Impeller Speed of the GranulationUnit, Compaction Force and Gap Width

09 Jun 2023 | Contributor(s): Wilms, Annika, Teske, Andreas, Meier, Robin, Wiedey, Raphael, Kleinebudde, Peter

Purpose: In continuous manufacturing of pharmaceuticals, dry granulation is of interest because of its large throughput capacity and energy efficiency. In order to manufacture solid oral dosage forms continuously, valid control strategies for critical quality attributes should be established. To...

Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation

09 Jun 2023 | Contributor(s): Vanhoorne, V., Bekaert, B., Peeters, E., De Beer, T., Remon, J-P., Vervaet, C.

In most formulations processed via continuous twin screw granulation microcrystalline cellulose (MCC) and/or lactose are used as excipients, but mannitol is also a preferred excipient for wet granulation and tableting due to its non-hygroscopicity and inertness. Therefore, the aim of the current...

Improving chemical synthesis using flow reactors

09 Jun 2023 | Contributor(s): Wiles, C, Watts, P

Owing to the competitive nature of the pharmaceutical industry, Research Articleers involved in lead compound generation are under continued pressure to identify and develop promising programmes of Research Article in order to secure intellectual property. The potential of a compound for...

Improving Feedability of Highly Adhesive Active Pharmaceutical Ingredients by Silication

09 Jun 2023 | 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...

Improving Pellet Quality in a Pharmaceutical Hot Melt Extrusion Process via PID Control and LOLIMOT-Based MPC

09 Jun 2023 | Contributor(s): Rehrl, J, Kirchengast, MCelikovic, S, Sacher, S, Kruisz, J, Khinast, J, Horn, M

Purpose The aim of this paper is the development of a process control concept for a hot melt extrusion (HME) and pelletization process. The new concept should improve the particle size distribution of the pellets produced. Methods Production of pellets containing an active pharmaceutical...

In line monitoring of the powder flow behavior and drug content in a Fette 3090 feed frame at different operating conditions using Near Infrared spectroscopy

09 Jun 2023 | Contributor(s): Sierra-Vega, Nobel, Sánchez-Paternina, Adriluz, Maldonado, Nadja, Cárdenas, Vanessa, Romañach, Rodolfo, Mendez, Rafael

Near infrared (NIR) spectroscopy was used to determine the drug concentration in 3% (w/w) acetaminophen blends within the complex flow regime of the tablet press feed frame just before tablet compaction. NIR spectra also provided valuable information on the powder flow behavior within the feed...

In Situ Characterization of Waters of Hydration in a Variable-Hydrate Active Pharmaceutical Ingredient Using Cl-35 Solid-State NMR and X-ray Diffraction

09 Jun 2023 | Contributor(s): Hirsh, DA, Holmes, STChakravarty, P, Peach, AA, DiPasquale, AG, Nagapudi, K, Schurko, RW

Variable-hydrate active pharmaceutical ingredients (APIs) are known to form thermodynamically and kinetically stabilized solid phases over a continuous range of nonstoichiometric hydration levels. Some of these forms can be problematic in the production of solid dosage forms (e.g., tablets and...

In Vitro Performance Tests for Continuous Manufacturing: The Impact on the Current Compendial Framework from the Viewpoint of the USP New Advancements in Product Performance Testing Expert

09 Jun 2023 | Contributor(s): Li, Hanlin Li, Nir, Ishai, Hermans, Andre, Fahmy, Raafat, Lu, Xujin, Biba, Edmond, Coutant, Carrie A.

As continuous manufacturing (CM) evolves from an emerging to widely adopted technology by industry in drug productmanufacturing, the compendiaI framework in product performance testing is also being evaluated for its applicability inCM. As such, the CM Working Group of the New Advancements in...

Incorporating Solvent-Dependent Kinetics To Design a Multistage, Continuous, Combined Cooling/Antisolvent Crystallization Process

09 Jun 2023 | Contributor(s): Schall, JM, Capellades, GMandur, JS, Braatz, RD, Myerson, AS

Combined cooling and antisolvent crystallization enables crystallization of many pharmaceutical products, but its process design typically neglects solvent composition influences on crystallization kinetics. This paper evaluates the influence of solvent-dependent nucleation and growth kinetics on...

In-Depth Evaluation of Data Collected During a Continuous Pharmaceutical Manufacturing Process: A Multivariate Statistical Process Monitoring Approach

09 Jun 2023 | Contributor(s): Silva, Ana F., Vercruysse, Jurgen, Vervaet, Chris, Remon, Jean P., Lopes, João A., De Beer, Thomas, Sarraguça, Mafalda C.

The present work presents an in-depth evaluation of continuously collected data during a twin-screw granulation and drying process performed on a continuous manufacturing line. During operation, the continuous line logs 49 univariate process variables, hence generating a large amount of data....

Indirect monitoring of ultralow dose API content in continuous wet granulation and tableting by machine vision

09 Jun 2023 | Contributor(s): Ficzere, Máté, Mészáros, Lilla Alexandra, Madarász, Lajos, Novák, Márk, Nagy, Zsombor Kristóf, Galata, Dorián László

This paper presents new machine vision–based methods for indirect real-time quantification of ultralow drug content during continuous twin-screw wet granulation and tableting. Granulation was performed with a solution containing carvedilol (CAR) as API in the ultralow dose range (0.05 w/w% in the...