Why flow means green - Evaluating the merits of continuous processing in the context of sustainability

09 Jun 2023 | Contributor(s): Dallinger, D, Kappe, CO

Enhanced heat and mass transfer, precise residence time control, shorter process times, increased safety, reproducibility, better product quality and easy scalability are just a few of the advantages of flow chemistry and reason for the increasing implementation of continuous processes not only...

Why We Need Continuous Pharmaceutical Manufacturing and How to Make It Happen

09 Jun 2023 | Contributor(s): Clive Badman, Charles L.Cooney, Alastair Florence, Konstantin Konstantinov, Markus Krumme, Salvatore Mascia, Moheb Nasr, Bernhardt L. Trout

We make the case for why continuous pharmaceutical manufacturing is essential, what the barriers are, and how to overcome them. To overcome them, government action is needed in terms of tax incentives or regulatory incentives that affect time.

Understanding pharmaceutical quality by design

09 Jun 2023 | Contributor(s): Yu, Lawrence X, Amidon, Gregory Khan, Mansoor A Hoag, Stephen W, Polli, James, Raju, G K, Woodcock, Janet

This review further clarifies the concept of pharmaceutical quality by design (QbD) and describes its objectives. QbD elements include the following: (1) a quality target product profile (QTPP) that identifies the critical quality attributes (CQAs) of the drug product; (2) product design and...

Use of a continuous twin screw granulation and drying system during formulation development and process optimization

09 Jun 2023 | Contributor(s): Vercruysse, J., Peeters, E., Fonteyne, M., Cappuyns, P., Delaet, U., Van Assche, I., De Beer, T., Remon, J. P., Vervaet, C.

Since small scale is key for successful introduction of continuous techniques in the pharmaceutical industry to allow its use during formulation development and process optimization, it is essential to determine whether the product quality is similar when small quantities of materials are...

Use of near-infrared spectroscopy to quantify drug content on a continuous blending process: Influence of mass flow and rotation speed variations

09 Jun 2023 | Contributor(s): Martínez, Lizbeth, Peinado, Antonio, Liesum, Lorenz, Betz, Gabriele

The aim of this study was to develop a quantitative Near-Infrared (NIR) method which monitors the homogeneity of a pharmaceutical formulation coming out of a continuous blender. For this purpose, a NIR diode array spectrometer with fast data acquisition was selected. Additionally, the dynamic...

Use of Terahertz-Raman Spectroscopy to Determine Solubility of the Crystalline Active Pharmaceutical Ingredient in Polymeric Matrices during Hot Melt Extrusion

09 Jun 2023 | Contributor(s): Bordos, E, Islam, MTFlorence, AJ, Halbert, GW, Robertson, J

Polymer-based amorphous solid dispersions (ASDs) comprise one of the most promising formulation strategies devised to improve the oral bioavailability of poorly water-soluble drugs. Exploitation of such systems in marketed products has been limited because of poor understanding of physical...

Use of the channel fill level in defining a design space for twin screw wet granulation

09 Jun 2023 | Contributor(s): Gorringe, L. J., Kee, G. S., Saleh, M. F., Fa, N. H., Elkes, R. G.

Twin screw wet granulation is a key process in the continuous manufacture of oral solid dosage forms. Previous Research Article has qualitatively suggested that the channel fill level influences the granules produced. In this paper a quantitative measure of the total volumetric fraction of the...

Using a material property library to find surrogate materials for pharmaceutical process development

09 Jun 2023 | Contributor(s): Escotet-Espinoza, MS, Moghtadernejad, SScicolone, J, Wang, YF, Pereira, G, Schafer, E, Vigh, T, Klingeleers, D, Ierapetritou, M, Muzzio, FJ

Material properties are known to have a significant impact on pharmaceutical manufacturing performance, particularly for solid product processes. Evaluating the performance of a specific material, for example an active pharmaceutical ingredient or excipient, is critical during development stages...

Using online mass spectrometry to predict the end point during drying of pharmaceutical products

09 Jun 2023 | Contributor(s): Dodda, Aditya G., Saranteas, Kostas, Henson, Michael A.

Drying of active pharmaceutical ingredients (APIs) is an energy-intensive process that is often a manufacturing bottleneck due to the relatively long processing times. A key objective is the ability to determine the drying end point, the time at which all solvent has been evaporated from the...

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...

Using residence time distribution in pharmaceutical solid dose manufacturing–A critical review

09 Jun 2023 | Contributor(s): Bhalode, Pooja, Tian, Huayu Gupta, Shashwat Razavi, Sonia M Roman-Ospino, Andres Talebian, Shahrzad Singh, Ravendra Scicolone, James V Muzzio, Fernando J, Ierapetritou, Marianthi

While continuous manufacturing (CM) of pharmaceutical solid-based drug products has been shown to be advantageous for improving the product quality and process efficiency in alignment with FDA’s support of the quality-by-design paradigm (Lee, 2015; Ierapetritou et al., 2016; Plumb, 2005; Schaber,...

Using Residence Time Distributions (RTDs) to Address the Traceability of Raw Materials in Continuous Pharmaceutical Manufacturing

09 Jun 2023 | Contributor(s): Engisch, William, Muzzio, Fernando

Continuous processing in pharmaceutical manufacturing is a relatively new approach that has generated significant attention. While it has been used for decades in other industries, showing significant advantages, the pharmaceutical industry has been slow in its adoption of continuous processing,...

Validation of a continuous granulation process using a twin-screw extruder

09 Jun 2023 | Contributor(s): Van Melkebeke, B., Vervaet, C., Remon, J. P.

Using twin-screw granulation as particle size enlargement technique, the effect of modifying the screw configuration (number of mixing zones, configuration of kneading block) on granule quality, tablet properties and mixing efficiency was investigated. The amount of oversized agglomerates and...

Towards medicinal mechanochemistry: evolution of milling from pharmaceutical solid form screening to the synthesis of active pharmaceutical ingredients (APIs)

09 Jun 2023 | Contributor(s): Tan, D, Loots, L, Friscic, T

This overview highlights the emergent area of mechanochemical reactions for making active pharmaceutical ingredients (APIs), and covers the latest advances in the recently established area of mechanochemical screening and synthesis of pharmaceutical solid forms, specifically polymorphs,...

TPLS as predictive platform for twin-screw wet granulation process and formulation development

09 Jun 2023 | Contributor(s): Ryckaert, A., Van Hauwermeiren, D., Dhondt, J., De Man, A., Funke, A., Djuric, D., Vervaet, C., Nopens, I., De Beer, T.

In recent years, the interest in continuous manufacturing techniques, such as twin-screw wet granulation, has increased. However, the understanding of the influence of the combination of raw material properties and process settings upon the granule quality attributes is still limited. In this...

Tracking raw material flow through a continuous direct compression line. Part II of II: Predicting dynamic changes in quality attributes of tablets due to disturbances in raw material properties using an independent residence time distribution model

09 Jun 2023 | Contributor(s): Peterwitz, M, Buchgeister, SMeier, R, Schembecker, G

Continuous manufacturing of pharmaceuticals promises many advantages regarding economics and quality. However, tracing deviating material in such processes is much more challenging than in batch processes due to axial back-mixing. The literature has proven the traceability of disturbances in the...

Transfer from High-Shear Batch to Continuous Twin Screw Wet Granulation: A Case Study in Understanding the Relationship Between Process Parameters and Product Quality Attributes

09 Jun 2023 | Contributor(s): Beer, Paul, Wilson, David, Huang, Zhenyu, De Matas, Marcel

A twin screw to high-shear batch granulation technology switch was evaluated for a pharmaceutical development project. Differences in granule (particle size distribution and porosity) and tablet (dissolution) quality attributes were analysed for both continuous and batch technologies. Liquid to...

Tuning Morphology in Active Pharmaceutical Ingredients: Controlling the Crystal Habit of Lovastatin through Solvent Choice and Non-Size-Matched Polymer Additives

09 Jun 2023 | Contributor(s): Hatcher, LE, Li, WPayne, P, Benyahia, B, Rielly, CD, Wilson, CC

Additive crystallization routes to control the crystal habit of the active pharmaceutical ingredient (API) lovastatin are presented, at small scale up to 25 mL. Lovastatin is an archetypical example of an API that forms needle-like crystals via solution-based recrystallization, causing issues for...

Twin Screw Continuous Wet Granulation

09 Jun 2023 | Contributor(s): Shah, Ankita V., Serajuddin, Abu T. M.

Granulation has become an integral part of the formulation of tablets. Wet granulation and roller compaction, which were developed over 50 years ago in the 1950s and 1960s, are still the most commonly used granulation methods in the pharmaceutical industry. However, these are batch processes and...

Twin screw granulation - review of current progress

09 Jun 2023 | Contributor(s): Thompson, M. R.

Twin screw granulation (TSG) is a new process of interest to the pharmaceutical community that can continuously wet granulate powders, doing so at lower liquid concentrations and with better product consistency than found by a high shear batch mixer. A considerable body of Research Article has...

Twin screw granulation as a simple and efficient tool for continuous wet granulation

09 Jun 2023 | Contributor(s): Keleb, EI, Vermeire, A, Vervaet, C, Remon, JP

The modification of a twin screw extruder for continuous wet granulation was investigated. Modification of the extruder setup as well as the screw design allowed the continuous wet granulation of alpha-lactose monohydrate without the need of a wet sieving step. The robustness of twin screw...

Twin Screw Granulation: Effects of Properties of Primary Powders

09 Jun 2023 | Contributor(s): Lute, Sushma, V, Dhenge, Ranjit M., Salman, Agba D.

Lactose and mannitol are some of the most commonly used powders in the pharmaceutical industry. The limited Research Article published so far highlights the effects of process and formulation parameters on the properties of the granules and the tablets produced using these two types of powders...

Twin-screw granulation and high-shear granulation: The influence of mannitol grade on granule and tablet properties

09 Jun 2023 | Contributor(s): Megarry, Andrew, Taylor, Agnes, Gholami, Aida, Wikstrom, Hakan, Tajarobi, Pirjo

Granule structure has a key influence on tablet critical quality attributes. The ability to control this structure through excipient choice is an important part of formulation development. Mannitol is a popular diluent and the choice of input grade has been shown to impact granule properties....

Twin-screw melt granulation: Current progress and challenges

09 Jun 2023 | Contributor(s): Kittikunakorn, Nada, Liu, Tongzhou, Zhang, Feng

Twin-screw melt granulation (TSMG) is a new alternative method for granulation that offers several advantages over wet and dry granulation methods. TSMG has rapidly gained interest over recent years in the pharmaceutical industry. Since it is an inherently continuous process with controlled...

Two-Stage Crystallizer Design for High Loading of Poorly Water-Soluble Pharmaceuticals in Porous Silica Matrices

09 Jun 2023 | Contributor(s): Dwyer, L, Kulkarni, SRuelas, L, Myerson, A

While porous silica supports have been previously studied as carriers for nanocrystalline forms of poorly water-soluble active pharmaceutical ingredients (APIs), increasing the loading of API in these matrices is of great importance if these carriers are to be used in drug formulations. A...