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Granulation development in batch-to-batch and continuous processes from a quality by design perspective
Contributor(s):: Ko, Seung Jin, Lee, Ju-Hyun, Kang, Chin-Yang, Park, Jun-Bom
The process of quality by design (QbD) is of great importance in drug development. This review describes the design of experiments (DoE) method, which is an important component of QbD. DoE is predominantly divided into a screening phase and an optimization phase. The screening phase uses...
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Flow and bulk density enhancements of pharmaceutical powders using a conical screen mill: A continuous dry coating device
Contributor(s):: Huang, ZH, Scicolone, JV, Gurumuthy, L, Dave, RN
The conical screen mill or Comil, a powder delumping device, was investigated due to its recent success as a continuously operated dry coater, The improvements in packing and flowability for different size grades of active pharmaceutical ingredients (APls) (acetaminophen, ibuprofen, and ascorbic...
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Flowsheet Models Modernize Pharmaceutical Manufacturing Design and Risk Assessment
Contributor(s):: Muzzio, Fernando, Singh, M Sebastian Escotet-Espinoza Ravendra, Lee Sau, Thomas O’Connor Marianthi, Ierapetritou, Lee Sharmista Chatterjee Rohit Ramachandran, Sen, Maitraye
The pharmaceutical industry has recognized the value of implementing a systematic approach to drug product development where quality is built into the product and process. The FDA initiative on quality by design (QbD) promotes the design of the product and manufacturing process using principles...
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Fluidization characterization in the ConSigma 25 dryer via process data - A method of advanced quality assurance in continuous manufacturing
Contributor(s):: Rehrl, Jakob, Hoermann-Kincses, Theresa, Sibanc, Rok, Hsiao, Wen-Kai, Franke, Meik, Khinast, Johannes
Wet granulation lines in pharmaceutical manufacturing facilities typically comprise a dryer that removes the excess moisture content after wet granulation. In this study, a semi-continuous dryer installed in the ConsiGma 25 wet granulation line was investigated. The goal was to highlight specific...
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Feasibility of Using Light-Induced Fluorescence Spectroscopy for Low-Dose Formulations Monitoring and Control
Contributor(s):: Igne, Benoît, Baldasano, Caitlin, Airiau, Christian
Purpose: Light-induced fluorescence was evaluated as a process analytical tool in the development of quantitative models for themonitoring of a low-dose formulation manufacturing process. Method: The system, equipped with a probe, was positioned in a tablet press feed-frame to monitor the active...
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Feed frame: The last processing step before the tablet compaction in pharmaceutical manufacturing
Contributor(s):: Sierra-Vega, Nobel, Romañach, Rodolfo J., Méndez, Rafael
The feed frame is a force-feeding device used in the die filling process. The die filling process is crucial within pharmaceutical manufacturing to guarantee the critical quality attributes of the tablets. In recent years, interest in this unit has increased because it can affect the properties...
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Feeding of particle-based materials in continuous solid dosage manufacturing: a material science perspective
Contributor(s):: Hsiao, WK, Hormann, TR, Toson, P, Paudel, A, Ghiotti, P, Stauffer, F, Bauer, F, Lakio, S, Behrend, O, Maurer, R, Holman, J, Khinast, J
The pharmaceutical industry today is experiencing a paradigm shift from batch to continuous manufacturing, which promises greater flexibility to target diverse populations, as well as more-consistent product quality to ensure best efficacy. However, shifting to continuous processing means that...
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Fine grade engineered microcrystalline cellulose excipients for direct compaction: Assessing suitability of different dry coating processes
Contributor(s):: Chen, Liang, He, Zizhou, Kunnath, Kuriakose, Zheng, Kai, Kim, Sangah, Dave, Rajesh N.
Recent work showed that contrary to conventional wisdom, fine surface engineered excipients outperform their larger counterparts in blends of highly loaded blends of cohesive drug powders in terms of their packing, flowability and tablet tensile strength. Here, two continuous devices, fluid...
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Fit-for-Purpose Miniature NIR Spectroscopy for Solid Dosage Continuous Manufacturing
Contributor(s):: Karry, Krizia, Singh, Ravendra, Muzzio, Fernando
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Evaluation of Hot-Melt Extrusion and Injection Molding for Continuous Manufacturing of Immediate-Release Tablets
Contributor(s):: Melocchi, Alice, Loreti, Giulia, Del Curto, Maria Dorly, Maroni, Alessandra, Gazzaniga, Andrea, Zema, Lucia
The exploitation of hot-melt extrusion and injection molding for the manufacturing of immediate-release (IR) tablets was preliminarily investigated in view of their special suitability for continuous manufacturing, which represents a current goal of pharmaceutical production because of its...
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Evaluation of spin freezing versus conventional freezing as part of a continuous pharmaceutical freeze-drying concept for unit doses
Contributor(s):: De Meyer, L., Van Bockstal, P. -J., Corver, J., Vervaet, C., Remon, J. P., De Beer, T.
Spin-freezing as alternative freezing approach was evaluated as part of an innovative continuous pharmaceutical freeze-drying concept for unit doses. The aim of this paper was to compare the sublimation rate of spin-frozen vials versus traditionally frozen vials in a batch freeze-dryer, and its...
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Evaluation of the lubrication mechanism at various rotation speeds and granule filling levels in a container mixer using a thermal effusivity sensor
Contributor(s):: Uchiyama, Jumpei, Aoki, Shigeru
To Research Article the detailed mechanism of the lubrication process using the thermal effusivity sensor, the relationships of the lubrication progress with the pattern of powder flow, the rotation speed and the filling level were investigated. The thermal effusivity profile was studied as a...
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Examining drug hydrophobicity in continuous wet granulation within a twin screw extruder
Contributor(s):: Li, H., Thompson, M. R., O'Donnell, K. P.
The influence of active pharmaceutical ingredient (API) hydrophobicity on continuous wet granulation was studied in twin screw granulation utilizing foamed binder delivery. The APIs examined were caffeine, acetaminophen, ibuprofen and griseofulvin and the drug load was maintained constant at 15...
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Exceptional Events Management Applied to Roller Compaction of Pharmaceutical Powders
Contributor(s):: Hamdan, Intan Munirah, Reklaitis, Gintaras V., Venkatasubramanian, Venkat
Introduction This study focuses on the development and implementation of an Exceptional Events Management (EEM) framework that detects, diagnoses, and mitigates exceptional events inherent to particulate processes that are prevalent in the pharmaceutical industry. Methods The EEM framework...
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Experimental determination of residence time distribution in continuous dry granulation
Contributor(s):: Mangal, Haress, Kleinebudde, Peter
With increasing importance of continuous manufacturing, the interest in integrating dry granulation into a continuous manufacturing line is growing. Residence time distribution measurements are of importance as they provide information about duration of materials within the process. These data...
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Experimental study of the stirring conditions taking place in a pilot plant continuous mixer of particulate solids
Contributor(s):: Marikh, K, Berthiaux, H, Mizonov, V, Barantsev, E
This work focuses on the characterisation and quantification of the stirring action that takes place inside a continuous mixer of particulate solids, under several operating conditions. Pure products, as well as 50% mass mixtures, are investigated to provide a basis for a better prediction of the...
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Exploratory studies in heat-assisted continuous twin-screw dry granulation: A novel alternative technique to conventional dry granulation
Contributor(s):: Kallakunta, Venkata Raman, Patil, Hemlata, Tiwari, Roshan, Ye, Xingyou, Upadhye, Sampada, Vladyka, Ronald S., Sarabu, Sandeep, Kim, Dong Wuk, Bandari, Suresh, Repka, Michael A.
Dry granulation is the preferred technique for solvent-sensitive products, especially drugs with stability problems such as hydrolysis. Twin-screw granulation is a continuous granulation technique, offering a potential alternative to conventional dry granulation techniques such as roller...
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End-to-End Continuous Manufacturing of Pharmaceuticals: Integrated Synthesis, Purification, and Final Dosage Formation
Contributor(s):: Mascia, Salvatore, Heider, Patrick L., Zhang, Haitao, Lakerveld, Richard, Benyahia, Brahim, Barton, Paul I., Braatz, Richard D., Cooney, Charles L., Evans, James M. B., Jamison, Timothy F., Jensen, Klavs F., Myerson, Allan S., Trout, Bernhardt L.
A series of tubes: The continuous manufacture of a finished drug product starting from chemical intermediates is reported. The continuous pilot-scale plant used a novel route that incorporated many advantages of continuous-flow processes to produce active pharmaceutical ingredients and the drug...
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Enhancing the Poor Flow and Tableting Problems of High Drug-Loading Formulation of Canagliflozin Using Continuous Green Granulation Process and Design-of-Experiment Approach
Contributor(s):: Almutairy, Bjad K., Khafagy, El-Sayed, Alalaiwe, Ahmed, Aldawsari, Mohammed F., Alshahrani, Saad M., Alsulays, Bader B., Alshetaili, Abdullah S., Alshehri, Sultan M, Fayed, Mohamed H.
Maximization of drug-loading can significantly reduce the size of dosage form and consequently decrease the cost of manufacture. In this Research Article, two challenges were addressed: poor flow and tableting problems of high-drug loading (>70%) formulation of canagliflozin (CNG), by adopting...
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Ensuring tablet quality via model-based control of a continuous direct compaction process
Contributor(s):: Kirchengast, M, Celikovic, SRehrl, J, Sacher, S, Kruisz, J, Khinast, J, Horn, M
Switching from batch to continuous pharmaceutical production offers several advantages, such as an increased productivity, a steady product quality, and decreased costs. This paper presents a control strategy for direct compaction on a continuous tablet production line consisting of two feeders,...
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Evaluating the potential for optimization of axial back-mixing in continuous pharmaceutical manufacturing
Contributor(s):: Peterwitz, M, Schembecker, G
In continuous pharmaceutical manufacturing, the degree of back-mixing has two contrary effects on the propagation of disturbances through a process. Firstly, back-mixing results in the contamination of adjacent material by strong disturbances and additional losses. However, the available...
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Evaluation of an in-line NIR spectroscopic method for the determination of the residence time in a tablet press
Contributor(s):: De Leersnyder, Fien, Vanhoorne, Valérie, Kumar, Ashish, Vervaet, Chris, De Beer, Thomas
In the current study, the ability to use in-line NIR inside the feed frame of a tablet press to monitor the residence time distribution inside the tablet press was investigated. Pulse-response experiments were performed. In-line measurements inside the feed frame were compared to measurements on...
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Evaluation of Analytical and Sampling Errors in the Prediction of the Active Pharmaceutical Ingredient Concentration in Blends From a Continuous Manufacturing Process
Contributor(s):: Vargas, Jenny, Roman-Ospino, Andres, Sanchez, Eric, Romañach, Rodolfo
Purpos: A near-infrared (NIR) spectroscopic method was developed for real time analysis of the active pharmaceutical ingredient (API) in blends from a continuous manufacturing process. The sampling and analytical errors of these determinations were estimated through variographic analysis....
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Effects of powder flow properties and shear environment on the performance of continuous mixing of pharmaceutical powders
Contributor(s):: Vanarase, AU, Osorio, JG, Muzzio, FJ
This paper focuses on two aspects of continuous powder mixing, namely characterizing the effects of material properties on the bulk powder flow behavior, and developing continuous blending strategies suitable for cohesive materials. The relative effects of process parameters and material...
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Effects of Process and Design Parameters on Granule Size Distribution in a Continuous High Shear Granulation Process
Contributor(s):: Meng, Wei, Oka, Sarang, Liu, Xue, Omer, Thamer, Ramachandran, Rohit, Muzzio, Fernando J.
Wet granulation is widely used in the pharmaceutical industry. This advantageous technology is capable of enhancing compression and powder handling, decreasing ingredient segregation, and promoting blend and content uniformity. Currently, a high level of interest exists in the continuous version...