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Process Analytical Technology Tools for Monitoring Pharmaceutical Unit operations: A Control Strategy for Continuous Process Verification
Contributor(s):: Kim, Eun, Kim, Ji, Kim, Min-Soo, Jeong, Seong, Choi, Du
Various frameworks and methods, such as quality by design (QbD), real time release test (RTRT), and continuous process verification (CPV), have been introduced to improve drug product quality in the pharmaceutical industry. The methods recognize that an appropriate combination of process controls...
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Process Design and Control of a Twin Screw Hot Melt Extrusion for Continuous Pharmaceutical Tamper-Resistant Tablet Production
Contributor(s):: Baronsky-Probst, J., Möltgen, C.-V., Kessler, W., Kessler, R.W.
Hot melt extrusion (HME) is a well-known process within the plastic and food industries that has been utilized for the past several decades and is increasingly accepted by the pharmaceutical industry for continuous manufacturing. For tamper-resistant formulations of e.g. opioids, HME is the most...
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Process design applied to optimise a directly compressible powder produced via a continuous manufacturing process
Contributor(s):: Gonnissen, Y., Goncalves, S. I. V., De Geest, B. G., Remon, J. P., Vervaet, C.
Manufacturing of 'ready-to-compress' powder mixtures for direct compression was performed by spray drying, without granulation, milling and/or blending steps in between spray drying and compaction. Powder mixtures containing acetaminophen, mannitol, erythritol, maltodextrin, crospovidone,...
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Predicting film thickness on film coated tablets
Contributor(s):: Rowe, RC
Film thicknesses on film coated tablets have been predicted based on the assumption that the increase in volume of a tablet core after coating is a result of a uniform thickness of polymer coating, i.e. a calculation of the dry volume increase in film coating per unit area of a tablet surface...
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Predicting Pharmaceutical Particle Size Distributions Using Kernel Mean Embedding
Contributor(s):: Van Hauwermeiren, Daan, Stock, Michiel, De Beer, Thomas, Nopens, Ingmar
In the pharmaceutical industry, the transition to continuous manufacturing of solid dosage forms is adopted by more and more companies. For these continuous processes, high-quality process models are needed. In pharmaceutical wet granulation, a unit operation in the ConsiGmaTM-25 continuous...
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Prediction of quality attributes of continuously produced granules using complementary PAT tools
Contributor(s):: Fonteyne, Margot, Soares, Sandra, Vercruysse, Jurgen, Peeters, Elisabeth, Burggraeve, Anneleen, Vervaet, Chris, Remon, Jean Paul, Sandler, Niklas, De Beer, Thomas
Manufacturers of pharmaceutical solid dosage forms aim for a reduced production time and a shorter‘‘time-to-market.’’ Therefore, continuous manufacturing gains increasing interest in the pharmaceutical industry. For continuous manufacturing, the quality of produced pharmaceuticals should be...
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Prediction of segregation tendency occurrence in dry particulate pharmaceutical mixtures: Development of a mathematical tool adapted for granular systems application
Contributor(s):: Abatzoglou, N;, Simard, JS
Segregation phenomena are of importance in nearly all processes involving dry granular and powder mixtures. The extent of segregation directly influences the eventual rejection of a considerable percentage of the final product in the majority of pharmaceutical processes; among these are those...
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Prediction of tablet weight variability in continuous manufacturing
Contributor(s):: Razavi, Sonia M., Scicolone, James, Snee, Ronald D., Kumar, Ashish, Bertels, Johny, Cappuyns, Philippe, Van Assche, Ivo, Cuitino, Alberto M, Muzzio, Fernando
This paper provides a method for prediction of weight variability of tablets made in rotary tablet presses as a function of material attributes and processing parameters. The goal was to be able to predict whether or not a formulation is suitable for direct compaction continuous manufacturing...
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Predictive Model-Based Process Start-Up in Pharmaceutical Continuous Granulation and Drying
Contributor(s):: Pauli, Victoria, Kleinebudde, Peter, Krumme, Markus
Continuous manufacturing (CM) is a promising strategy to achieve various benefits in the context of quality, flexibility, safety and cost in pharmaceutical production. One of the main technical challenges of CM is that the process needs to handle transient conditions such as the start-up phase...
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Pharmaceutical manufacturing and the quality by design (QBD), process analytical technology (PAT) approach
Contributor(s):: Murphy, Trevor, O’ Mahony, Niall, Panduru, Krishna, Riordan, Daniel, Walsh, Joseph
This paper is the result of a literature review focusing on the application of process analytical technology (PAT) for the pharmaceutical industry in conjunction with the quality by design (QBD) framework. PAT and the QBD framework put forward by the FDA, offer a holistic approach to...
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Powder composition monitoring in continuous pharmaceutical solid-dosage form manufacturing using state estimation-Proof of concept
Contributor(s):: Destro, Francesco, Munoz, Salvador Garcia, Bezzo, Fabrizio, Barolo, Massimiliano
In continuous solid-dosage form manufacturing, the powder feeding system is responsible for supplying downstream the correct formulation of the drug product ingredients. The composition of the powder delivered by the feeding system is inferred from the measurements of powder mass flow from the...
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Pharmaceutical Applications of Hot-Melt Extrusion: Continuous Manufacturing, Twin-Screw Granulations, and 3D Printing
Contributor(s):: Maniruzzaman , Mohammed
Recently, hot-melt extrusion (HME) techniques have been presented as innovative platforms to produce various pharmaceuticals. HME is an emerging processing technology used primarily for the manufacture of pharmaceutical solid dispersions. It also combines the advantages of a solvent-free process...
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Pharmaceutical excipients properties and screw feeder performance in continuous processing lines: a Quality by Design (QbD) approach
Contributor(s):: Santos, Bianca, Carmo, Flavia, Schlindwein, Walkiria, Muirhead, Gordon, Rodrigues, Carlos, Cabral, Lucio, Westrup, Julian, Pitt, Kendal
Screw feeder performance is a critical aspect in continuous manufacturing processes. Pharmaceutical excipients, such as mannitol, microcrystalline cellulose, lactose monohydrate, and anhydrous dibasic calcium phosphate can present problems in ensuring a continuous stable feed rate due to their...
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Pharmaceutical formulation and manufacturing using particle/powder technology for personalized medicines
Contributor(s):: Tahara, Kohei
Particle/powder technology is used in the manufacture of many pharmaceutical products, and Research Article on the physical properties of particles in the nano- to micro-particle range is important in the pharmaceutical field. The concept of precision medicine will require an increasing shift in...
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Parametric Study of Residence Time Distributions and Granulation Kinetics as a Basis for Process Modeling of Twin-Screw Wet Granulation
Contributor(s):: Plath, Timo, Korte, Carolin, Sivanesapillai, Rakulan, Weinhart, Thomas
Twin-screw wet granulation is a crucial unit operation in shifting from pharmaceutical batch to continuous processes, but granulation kinetics as well as residence times are yet poorly understood. Experimental findings are highly dependent on screw configuration as well as formulation, and thus...
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On-line monitoring of blend uniformity in continuous drug product manufacturing process -The impact of powder flow rate and the choice of spectrometer: Dispersive vs. FT
Contributor(s):: Shi, Zhenqi, McGhehey, Kathryn C, Leavesley, Ian M., Manley, Leo F.
One of the commonly acknowledged issues in continuous manufacturing of drug products is how to provide a representative sampling on flowing powder to assure its blend uniformity. An investigation was conducted to improve understanding on the impact of powder flow rate under different continuous...
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Opportunities for Process Control and Quality Assurance Using Online NIR Analysis to a Continuous Wet Granulation Tableting Line
Contributor(s):: Palmer J., O’Malley C.J., Wade M.J., Martin E.B., Page T., Montague G.A.
This paper investigates the application of online near-infrared measurements as a means to measure blend uniformity in a continuous tableting line. Underlying all the monitoring and control methods is the ability to measure key tablet properties online at a rate suitable for control purposes. The...
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Optimization of a semi-batch tablet coating process for a continuous manufacturing line by design of experiments
Contributor(s):: Barimani, Shirin, Šibanc, Rok, Kleinebudde, Peter
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Optimization of critical quality attributes in continuous twin-screw wet granulation via design space validated with pilot scale experimental data
Contributor(s):: Liu, Huolong, Galbraith, S. C., Ricart, Brendon, Stanton, Courtney, Smith-Goettler, Brandye, Verdi, Luke, O'Connor, Thomas, Lee, Sau, Yoon, Seongkyu
In this study, the influence of key process variables (screw speed, throughput and liquid to solid (L/S) ratio) of a continuous twin screw wet granulation (TSWG) was investigated using a central composite face-centered (CCF) experimental design method. Regression models were developed to predict...
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Optimization of residence time distribution in RCDG and an assessment of its applicability in continuous manufacturing
Contributor(s):: Wilms, Annika, Kleinebudde, Peter
Knowledge of residence time is a critical aspect in developing control and material diversion strategies for continuous manufacturing processes in pharmaceutical manufacturing. Dry granulation is a promising continuous granulation technique as it is fast and economical. In this study, a...
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Optimized continuous pharmaceutical manufacturing via model-predictive control
Contributor(s):: Rehrl, Jakob, Kruisz, Julia, Sacher, Stephan, Khinast, Johannes, Horn, Martin
This paper demonstrates the application of model-predictive control to a feeding blending unit used in continuous pharmaceutical manufacturing. The goal of this contribution is, on the one hand, to highlight the advantages of the proposed concept compared to conventional PI-controllers, and, on...
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Orthogonal Redundant Monitoring of a New Continuous Fluid-Bed Dryer for Pharmaceutical Processing by Means of Mass and Energy Balance Calculations and Spectroscopic Techniques
Contributor(s):: Pauli, Victoria, Elbaz, Frantz, Kleinebudde, Peter, Krumme, Markus
In line with the ongoing shift from batch to continuous pharmaceutical production of solid oral dosage forms, a novel continuous fluid-bed dryer was developed. The forced feed nature of the Glatt GPCG2 CM fluid-bed dryer allows continuous, first-in-first-out drying of wet granulate materials...
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On-Demand Continuous Manufacturing of Ciprofloxacin in Portable Plug-and-Play Factories: Development of a Highly Efficient Synthesis for Ciprofloxacin
Contributor(s):: Armstrong, Cameron, Miyai, Yuma, Formosa, Anna, Thomas Dale, Chen, Esther, Hart, Travis, Schultz, Victor, Desai, Bimbisar, Cai, Angela, Almasy, Alexandra, Jensen, Klavs, Roper, Thomas
The experimental approach taken and challenges overcome in developing a high-purity production (>100 g) scale process for the telescoped synthesis of the antibiotic ciprofloxacin is outlined. The process was first optimized for each step sequentially with regard to purity and yield, with...
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Near Infrared Method Development for a Continuous Manufacturing Blending Process
Contributor(s):: Colon, Yleana, Florian, Miguel, Acevedo, David, Mendez, Rafael, Romañach, Rodolfo
Purpose This study describes the validation of a near infrared spectroscopic method for monitoring a continuous manufacturing system. The achievement of this goal requires determining the near infrared (NIR) method’s accuracy, precision, obtaining an estimate of the sample volume analyzed, and...
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Near infrared spectroscopic calibration models for real time monitoring of powder density
Contributor(s):: Román-Ospino, Andrés, Singh, Ravendra, Ierapetritoua, Marianthi, Ramachandrana, Rohit, Mendez, Rafael, Ortega-Zuñiga, Carlos, Muzzio, Fernando, Romañach, Rodolfo
Near infrared spectroscopic (NIRS) calibration models for real time prediction of powder density (tap, bulk and consolidated) were developed for a pharmaceutical formulation. Powder density is a critical property in the manufacturing of solid oral dosages, related to critical quality attributes...