The use of Rheology Combined with Differential Scanning Calorimetry to Elucidate the Granulation Mechanism of an Immiscible Formulation During Continuous Twin-Screw Melt Granulation

09 Jun 2023 | Contributor(s): Monteyne, Tinne, Heeze, Liza, Mortier, Severine Therese F. C., Oldoerp, Klaus, Cardinaels, Ruth, Nopens, Ingmar, Vervaet, Chris, Remon, Jean-Paul, De Beer, Thomas

Twin screw hot melt granulation (TS HMG) is a valuable, but still unexplored alternative to continuous granulation of moisture sensitive drugs. However, knowledge of the material behavior during TS HMG is crucial to optimize the formulation, process and resulting granule properties. The aim of...

The use of rheology to elucidate the granulation mechanisms of a miscible and immiscible system during continuous twin-screw melt granulation

09 Jun 2023 | Contributor(s): Monteyne, Tinne, Heeze, Liza, Mortier, Severine Therese F. C., Oldorp, Klaus, Nopens, Ingmar, Remon, Jean-Paul, Vervaet, Chris, De Beer, Thomas

Twin-screw hot melt granulation (TS HMG) is a valuable, but still unexplored alternative to granulate temperature and moisture sensitive drugs in a continuous way. Recently, the material behavior of an immiscible drug-binder blend during TS HMG was unraveled by using a rheometer and differential...

Theory of Sampling (TOS): A necessary and sufficient guarantee for reliable multivariate dara analysis in pharmaceutical manufacturing

09 Jun 2023 | Contributor(s): Esbensen, Kim H, Romañach, Rodolfo, J.Ferrerira, Ana P., Menezes, Jose C., Tobyn, Mike, Román-Ospino, Andrés D.

Multivariate Analysis in the Pharmaceutical Industry provides industry practitioners with guidance on multivariate data methods and their applications over the lifecycle of a pharmaceutical product, from process development, to routine manufacturing, focusing on the challenges specific to each...

Thin-Film Evaporator Model for Continuous Active Pharmaceutical Ingredient Manufacturing

09 Jun 2023 | Contributor(s): Lee, BW, Yin, KHSplaine, K, Roesch, B

Thin-film evaporator (TFE) is a popular continuous distillation/evaporation technology for pharmaceutical and fine chemical industries and has several equipment and process configurations that make fundamental modeling approaches very challenging. Specifically, moving wipers and lack of fluid...

Toward Continuous Crystallization of Urea-Barbituric Acid: A Polymorphic Co-Crystal System

09 Jun 2023 | Contributor(s): Powell, KA, Bartolini, GWittering, KE, Saleemi, AN, Wilson, CC, Rielly, CD, Nagy, ZK

Pharmaceutical co-crystals are multicomponent molecular systems typically formed through hydrogen bonding of a co-former molecule with the active pharmaceutical ingredient (API). Just as many single component molecular structures can exhibit polymorphism due to the geometry of hydrogen bond...

Towards 4th industrial revolution efficient and sustainable continuous flow manufacturing of active pharmaceutical ingredients

09 Jun 2023 | Contributor(s): Sagandira, CR, Nqeketo, SMhlana, K, Sonti, T, Gaqa, S, Watts, P

Continuous flow chemistry has opened a new paradigm in both the laboratory and pharmaceutical industry. This review details the recently reported literature on continuous multistep telescoped synthesis of active pharmaceutical ingredients (APIs), inline flow downstream processing, in-process...

Towards a Continuous Manufacturing Process of Protein-Loaded Polymeric Nanoparticle Powders

09 Jun 2023 | Contributor(s): Schiller, Stefan, Hanefeld, Andrea, Schneider, Marc, Lehr, Claus-Michael

To develop a scalable and efficient process suitable for the continuous manufacturing of poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing ovalbumin as the model protein. PLGA nanoparticles were prepared using a double emulsification spray-drying method. Emulsions were prepared using...

Towards a Greener Pharmacy by More Eco Design

09 Jun 2023 | Contributor(s): Baron, M

This review proposes an overview of the main trends explored by the pharmaceutical industry in order to develop a greener and smarter pharmacy minimizing any negative impact to the environment, and using more sustainable processes and drugs. If many drugs have their origin in nature, many active...

Towards a novel continuous HME-Tableting line: Process development and control concept

09 Jun 2023 | Contributor(s): Sacher, Stephan, Celikovic, Selma, Rehrl, Jakob, Poms, Johannes, Kirchengast, Martin, Kruisz, Julia, Sipek, Martin, Salar-Behzadi, Sharareh, Berger, Hannes, Stark, Gerald, Horn, Martin, Khinast, Johannes G.

The objective of this study was to develop a novel closed-loop controlled continuous tablet manufacturing line, which first uses hot melt extrusion (HME) to produce pellets based on API and a polymer matrix. Such systems can be used to make complex pharmaceutical formulations, e.g., amorphous...

Towards Continuous Primary Manufacturing Processes-Particle Design through Combined Crystallization and Particle Isolation

09 Jun 2023 | Contributor(s): Steenweg, C, Kufner, ACHabicht, J, Wohlgemuth, K

Integrated continuous manufacturing processes of active pharmaceutical ingredients (API) provide key benefits concerning product quality control, scale-up capability, and a reduced time-to-market. Thereby, the crystallization step, which is used in approximately 90% of API productions, mainly...

The Influence of Equipment Design and Process Parameters on Granule Breakage in a Semi-Continuous Fluid Bed Dryer after Continuous Twin-Screw Wet Granulation

09 Jun 2023 | Contributor(s): Ryckaert, Alexander, Ghijs, Michael, Portier, Christoph, Djuric, Dejan, Funke, Adrian, Vervaet, Chris, De Beer, Thomas

The drying unit of a continuous from-powder-to-tablet manufacturing line based on twin-screw granulation (TSG) is a crucial intermediate process step to achieve the desired tablet quality. Understanding the size reduction of pharmaceutical granules before, during, and after the fluid bed drying...

The optimization of process analytical technology for the inline quantification of multiple drugs in fixed dose combinations during continuous processing

09 Jun 2023 | Contributor(s): Dadou, SM, Tian, YWLi, S, Jones, DS, Andrews, GP

Complications associated with uncontrolled hypertension are considered the major cause of premature death worldwide. Fixed-dose combinations (FDCs) offer an alternative approach to polypharmacy with the aim to improve patient compliance. Process Analytical Technology (PAT) is gaining momentum as...

The reality of in-line tablet coating

09 Jun 2023 | Contributor(s): Cahyadi, Christine, Chan, Lai Wah, Heng, Paul Wan Sia

The possibility of continuous processing in pharmaceutical tablet manufacturing is hampered by the viscoelastic recovery of tablets post-compaction. Compacted tablets are typically aged before coating to allow complete viscoelastic recovery so as to avoid subsequent coating defects. There has...

The route from problem to solution in multistep continuous flow synthesis of pharmaceutical compounds

09 Jun 2023 | 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 scope of PAT in real-time advanced control of tablet quality

09 Jun 2023 | Contributor(s): Singh, Ravendra, Ierapetritou, Marianthi, Ramachandran, Rohit

Continuous pharmaceutical manufacturing together with process analytical technology (PAT) provides a suitable platform for automatic feed-forward/feed-back (FF/FB) control of the end product quality as desired by quality by design (QbD)-based efficient manufacturing. The precise control of the...

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

09 Jun 2023 | Contributor(s): Baumann, M, Baxendale, IR

The implementation of continuous flow processing as a key enabling technology has transformed the way we conduct chemistry and has expanded our synthetic capabilities. As a result many new preparative routes have been designed towards commercially relevant drug compounds achieving more efficient...

The Use of Cooling Crystallization in an Ionic Liquid System for the Purification of Pharmaceuticals

09 Jun 2023 | Contributor(s): Weber, CC, Kulkarni, SAKunov-Kruse, AJ, Rogers, RD, Myerson, AS

The application of ionic liquids (ILs) as solvents is frequently discussed in the context of their tunability, with the potential to tailor the solvent system uniquely to the process being investigated. Instead, here we study the potential for a single IL, 1-ethyl-3-methylimidazohum...

The Use of Molecular Oxygen in Pharmaceutical Manufacturing: Is Flow the Way to Go?

09 Jun 2023 | Contributor(s): Hone, CA, Roberge, DM, Kappe, CO

Molecular oxygen is arguably the greenest reagent available to the organic chemist. Most commonly, a diluted form of oxygen gas, consisting of less than 10% O-2 in N-2 ("synthetic air"), is used in pharmaceutical and fine chemical batch manufacturing to effectively address safety concerns when...

The Use of Near-Infrared and Microwave Resonance Sensing to Monitor a Continuous Roller Compaction Process

09 Jun 2023 | Contributor(s): Austin, John, Gupta, Anshu, Mcdonnell, Ryan, Reklaitis, Gintaras V., Harris, Michael T

Roller compaction is commonly used in the pharmaceutical and nutraceutical industries to increase and narrow the size distribution of a particulate material, making it easier to process. Both the moisture content of the material and the density of the roller compacted ribbon affect the uniformity...

The Use of PAT and Off-line Methods for Monitoring of Roller Compacted Ribbon and Granule Properties with a View to Continuous Processing

09 Jun 2023 | Contributor(s): McAuliffe M.A.P., Omahony G.E., Blackshields C.A., Collins J.A., Egan D.P., Kiernan L., Oneill E., Lenihan S., Walker G.M., Crean A.M.

Real-time process monitoring using process analytical technology (PAT) tools can augment process understanding, enable improved process control, and hence facilitate the production of high-quality pharmaceutical products. While beneficial for batch processes, the availability of PAT tools to...

The development of an inline Raman spectroscopic analysis method as a quality control tool for hot melt extruded ramipril fixed-dose combination products

09 Jun 2023 | Contributor(s): Andres, G.P., Jones D.S., Senta-Loys Z., Almajaan A., Li S., Chevallier O., Elliot C., Healy A.M., Kelleher J.F., Madi A.M., Gilvary G.C., Tian Y.a

Currently in the pharmaceutical industry, continuous manufacturing is an area of significant interest. In particular, hot-melt extrusion (HME) offers many advantages and has been shown to significantly reduce the number of processing steps relative to a conventional product manufacturing line. To...

The effect of lubrication on density distributions of roller compacted ribbons

09 Jun 2023 | Contributor(s): Miguelez-Moran, A. M, Seville, J. P. K.

Roller compaction is a continuous dry granulation process for producing free flowing granules in order to increase the bulk density and uniformity of pharmaceutical formulations. It is a complicated process due to the diversity of powder blends and processing parameters involved. The properties...

The Effect of Mixer Properties and Fill Level on Granular Flow in a Bladed Mixer

09 Jun 2023 | Contributor(s): Remy, B, Glasser, BJ, Khinast, JG

The discrete element method was used to study the effect of mixer properties and fill level oil the granular flow of monodisperse, cohesionless spheres in a bladed mixer. For fill levels just covering the span of the blades, a three-dimensional (3-D) recirculation zone develops in front of the...

The effect of screw configuration and formulation variables on liquid requirements and granule quality in a continuous twin screw wet granulation process

09 Jun 2023 | Contributor(s): Vandevivere, L., Van Wijmeersch, E., Hausler, O., De Beer, T., Vervaet, C., Vanhoorne, V.

The effect of two screw configurations with varying stagger angle was evaluated on the liquid amount required to produce good quality granules for a highly (mannitol-based) and a poorly (DCP-based) soluble formulation containing different binders. It is generally known that the use of a higher...

The Effect of Ultrasound on the Crystallisation of Paracetamol in the Presence of Structurally Similar Impurities

09 Jun 2023 | Contributor(s): Nguyen, TTH, Khan, ABruce, LM, Forbes, C, O'Leary, RL, Price, CJ

Sono-crystallisation has been used to enhance crystalline product quality particularly in terms of purity, particle size and size distribution. In this work, the effect of impurities and ultrasound on crystallisation processes (nucleation temperature, yield) and crystal properties (crystal size...