The Transition from Batch to Continuous Manufacturing for Tablet Manufacturing

2021 ◽  
Author(s):  
Yi Yang
Keyword(s):  
Continuous Manufacturing ◽  
Tablet Manufacturing

scholarly journals Blend Segregation in Tablets Manufacturing and Its Effect on Drug Content Uniformity—A Review

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1909
Author(s):  
Emilia Jakubowska ◽  
Natalia Ciepluch
Keyword(s):  
Active Pharmaceutical Ingredient ◽  
Content Uniformity ◽  
Continuous Manufacturing ◽  
Compression Process ◽  
Factors Affecting ◽  
Die Filling ◽  
Drug Potency ◽  
Tablet Press ◽  
Tablet Manufacturing ◽  
Processing Factors

Content uniformity (CU) of the active pharmaceutical ingredient is a critical quality attribute of tablets as a dosage form, ensuring reproducible drug potency. Failure to meet the accepted uniformity in the final product may be caused either by suboptimal mixing and insufficient initial blend homogeneity, or may result from further particle segregation during storage, transfer or the compression process itself. This review presents the most relevant powder segregation mechanisms in tablet manufacturing and summarizes the currently available, up-to-date research on segregation and uniformity loss at the various stages of production process—the blend transfer from the bulk container to the tablet press, filling and discharge from the feeding hopper, as well as die filling. Formulation and processing factors affecting the occurrence of segregation and tablets’ CU are reviewed and recommendations for minimizing the risk of content uniformity failure in tablets are considered herein, including the perspective of continuous manufacturing.

scholarly journals Continuous citrate‐capped gold nanoparticle synthesis in a two‐phase flow reactor

2021 ◽  
Author(s):  
Spyridon Damilos ◽  
Ioannis Alissandratos ◽  
Luca Panariello ◽  
Anand N. P. Radhakrishnan ◽  
Enhong Cao ◽  
...  
Keyword(s):  
Particle Size ◽  
Gold Nanoparticles ◽  
Residence Time ◽  
Flow Reactor ◽  
Phase Flow ◽  
Continuous Manufacturing ◽  
Two Phase ◽  
Process Yield ◽  
Au Nps ◽  
Manufacturing Platform

AbstractA continuous manufacturing platform was developed for the synthesis of aqueous colloidal 10–20 nm gold nanoparticles (Au NPs) in a flow reactor using chloroauric acid, sodium citrate and citric acid at 95 oC and 2.3 bar(a) pressure. The use of a two-phase flow system – using heptane as the continuous phase – prevented fouling on the reactor walls, while improving the residence time distribution. Continuous syntheses for up to 2 h demonstrated its potential application for continuous manufacturing, while live quality control was established using online UV-Vis photospectrometry that monitored the particle size and process yield. The synthesis was stable and reproducible over time for gold precursor concentration above 0.23 mM (after mixing), resulting in average particle size between 12 and 15 nm. A hydrophobic membrane separator provided successful separation of the aqueous and organic phases and collection of colloidal Au NPs in flow. Process yield increased at higher inlet flow rates (from 70 % to almost 100 %), due to lower residence time of the colloidal solution in the separator resulting in less fouling in the PTFE membrane. This study addresses the challenges for the translation of the synthesis from batch to flow and provides tools for the development of a continuous manufacturing platform for gold nanoparticles.Graphical abstract

scholarly journals Applications of Supercritical Anti-Solvent Process in Preparation of Solid Multicomponent Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 475
Author(s):  
Guijin Liu ◽  
Junjian Li ◽  
Shiming Deng
Keyword(s):  
Solid State ◽  
Solid Dispersions ◽  
Crystal Form ◽  
Great Promise ◽  
Computational Techniques ◽  
Large Contribution ◽  
Continuous Manufacturing ◽  
Multicomponent Systems ◽  
On Line ◽  
Underlying Mechanisms

Solid multicomponent systems (SMS) are gaining an increasingly important role in the pharmaceutical industry, to improve the physicochemical properties of active pharmaceutical ingredients (APIs). In recent years, various processes have been employed for SMS manufacturing. Control of the particle solid-state properties, such as size, morphology, and crystal form is required to optimize the SMS formulation. By utilizing the unique and tunable properties of supercritical fluids, supercritical anti-solvent (SAS) process holds great promise for the manipulation of the solid-state properties of APIs. The SAS techniques have been developed from batch to continuous mode. Their applications in SMS preparation are summarized in this review. Many pharmaceutical co-crystals and solid dispersions have been successfully produced via the SAS process, where the solid-state properties of APIs can be well designed by controlling the operating parameters. The underlying mechanisms on the manipulation of solid-state properties are discussed, with the help of on-line monitoring and computational techniques. With continuous researching, SAS process will give a large contribution to the scalable and continuous manufacturing of desired SMS in the near future.

scholarly journals PAT for Continuous Chromatography Integrated into Continuous Manufacturing of Biologics towards Autonomous Operation

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 472
Author(s):  
Florian Lukas Vetter ◽  
Steffen Zobel-Roos ◽  
Jochen Strube
Keyword(s):  
Molecular Weight ◽  
Zero Point ◽  
Test System ◽  
Target Component ◽  
Array Detector ◽  
Continuous Manufacturing ◽  
Fluorescence Detector ◽  
Autonomous Operation ◽  
Side Component ◽  
Process Disturbances

This study proposes a reliable inline PAT concept for the simultaneous monitoring of different product components after chromatography. The feed for purification consisted of four main components, IgG monomer, dimer, and two lower molecular weight components of 4.4 kDa and 1 kDa molecular weight. The proposed measurement setup consists of a UV–VIS diode-array detector and a fluorescence detector. Applying this system, a R2 of 0.93 for the target component, a R2 of 0.67 for the dimer, a R2 of 0.91 for the first side component and a R2 of 0.93 for the second side component is achieved. Root mean square error for IgG monomer was 0.027 g/L, for dimer 0.0047 g/L, for side component 1 0.016 g/L and for the side component 2 0.014 g/L. The proposed measurement concept tracked component concentration reliably down to 0.05 g/L. Zero-point fluctuations were kept within a standard deviation of 0.018 g/L for samples with no IgG concentration but with side components present, allowing a reliable detection of the target component. The main reason inline concentration measurements have not been established yet, is the false-positive measurement of target components when side components are present. This problem was eliminated using the combination of fluorescence and UV–VIS data for the test system. The use of this measurement system is simulated for the test system, allowing an automatic fraction cut at 0.05 g/L. In this simulation a consistent yield of >99% was achieved. Process disturbances for processed feed volume, feed purity and feed IgG concentration can be compensated with this setup. Compared to a timed process control, yield can be increased by up to 12.5%, if unexpected process disturbances occur.

scholarly journals Identifying Critical Binder Attributes to Facilitate Binder Selection for Efficient Formulation Development in a Continuous Twin Screw Wet Granulation Process

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 210
Author(s):  
Lise Vandevivere ◽  
Maxine Vangampelaere ◽  
Christoph Portier ◽  
Cedrine de Backere ◽  
Olaf Häusler ◽  
...  
Keyword(s):  
Dissolution Kinetics ◽  
Wet Granulation ◽  
Continuous Manufacturing ◽  
Formulation Development ◽  
Granulation Process ◽  
Low Viscosity ◽  
Twin Screw ◽  
Poorly Soluble ◽  
Selection For ◽  
The Impact

The suitability of pharmaceutical binders for continuous twin-screw wet granulation was investigated as the pharmaceutical industry is undergoing a switch from batch to continuous manufacturing. Binder selection for twin-screw wet granulation should rely on a scientific approach to enable efficient formulation development. Therefore, the current study identified binder attributes affecting the binder effectiveness in a wet granulation process of a highly soluble model excipient (mannitol). For this formulation, higher binder effectiveness was linked to fast activation of the binder properties (i.e., fast binder dissolution kinetics combined with low viscosity attributes and good wetting properties by the binder). As the impact of binder attributes on the granulation process of a poorly soluble formulation (dicalcium phosphate) was previously investigated, this enabled a comprehensive comparison between both formulations in current research focusing on binder selection. This comparison revealed that binder attributes that are important to guide binder selection differ in function of the solubility of the formulation. The identification of critical binder attributes in the current study enables rational and efficient binder selection for twin-screw granulation of well soluble and poorly soluble formulations. Binder addition proved especially valuable for a poorly soluble formulation.

scholarly journals Effect of Aspect Ratio on the Mixing Performance in the Kenics Static Mixer

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 464
Author(s):  
Xingren Jiang ◽  
Ning Yang ◽  
Rijie Wang
Keyword(s):  
Pharmaceutical Industry ◽  
Aspect Ratio ◽  
Flow Reactor ◽  
Mixing Time ◽  
Continuous Process ◽  
Scale Up ◽  
Influence Factors ◽  
Continuous Manufacturing ◽  
Static Mixer ◽  
Mixing Performance

Continuous manufacturing has received increasing interest because of the advantages of intrinsic safety and enhanced mass transfer in the pharmaceutical industry. However, the difficulty for scale-up has limited the application of continuous manufacturing for a long time. Recently, the tubular flow reactor equipped with the Kenics static mixer appears to be a solution for the continuous process scale-up. Although many influence factors on the mixing performance in the Kenics static mixer have been investigated, little research has been carried out on the aspect ratio. In this study, we used the coefficient of variation as the mixing evaluation index to investigate the effect of the aspect ratio (0.2–2) on the Kenics static mixer’s mixing performance. The results indicate that a low aspect ratio helps obtain a shorter mixing time and mixer length. This study suggests that adjusting the aspect ratio of the Kenics static mixer can be a new strategy for the scale-up of a continuous process in the pharmaceutical industry.

Definition of a JA-2 Equivalent Propellant to be Produced by Continuous Solventless Extrusion

2013 ◽  
Vol 80 (3) ◽  
Author(s):  
Thelma G. Manning ◽  
Joseph Leone ◽  
Martijn Zebregs ◽  
Dinesh R. Ramlal ◽  
Chris A. van Driel
Keyword(s):  
Extrusion Process ◽  
Continuous Manufacturing ◽  
Twin Screw Extrusion ◽  
Extrusion Processing ◽  
Roll Mill ◽  
Screw Extrusion ◽  
Twin Screw ◽  
Ballistic Properties ◽  
Definition Of ◽  
Double Base

In order to eliminate residual solvents in ammunition and to reduce the emissions of volatile organic compounds to the atmosphere, the U.S. Army ARDEC has teamed with TNO in developing a new process for the production of solventless propellant for tank ammunition. To reduce the costs of solventless propellants production, shear roll mill and continuous extrusion processing was investigated. As described in this paper JA-2 a double base propellant cannot be processed without solvent by the extrusion process. An alternative JA-2 equivalent propellant was defined. The aim of this work is to demonstrate the manufacturing of this propellant by solventless continuous twin screw extrusion processing while maintaining gun performance characteristics of conventional JA-2 propellant. This is elucidated by explicitly researching the relationship between interior ballistic properties of the gun propellant and utilizing a continuous manufacturing process. Processing conditions were established, and the propellant was manufactured accordingly. The extruded propellant has the desired properties, which resulted in a comparable gun performance as the conventional JA-2 propellant.

Examples of NIR based real time release in tablet manufacturing

2007 ◽  
Vol 43 (4) ◽  
pp. 1297-1305 ◽  
Author(s):  
E.T.S. Skibsted ◽  
J.A. Westerhuis ◽  
A.K. Smilde ◽  
D.T. Witte
Keyword(s):  
Real Time ◽  
Tablet Manufacturing
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