Chemical Engineering Essentials, Volume 2 E-Book
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- Herausgeber: John Wiley & Sons
- Kategorie: Fachliteratur
- Serie: ISTE Invoiced
- Sprache: Englisch
In an era of rapid innovation and with a focus on sustainability, Chemical Engineering Essentials provides a definitive guide to mastering the discipline. Divided into two volumes, this series offers a seamless blend of foundational knowledge and advanced applications to address the evolving needs of academia and industry.
Volume 1 lays a strong foundation with topics such as material and energy balances, thermodynamics, phase equilibrium, fluid mechanics, transport phenomena, and essential separation processes such as distillation and membrane technologies.
This volume builds on these principles, delving into reaction engineering, reactor modeling with MATLAB and ASPEN PLUS, material properties, process intensification and nanotechnology. It also addresses critical global challenges, emphasizing green chemistry, waste minimization, resource recovery, and workplace safety.
Together, these volumes provide a holistic understanding of chemical engineering, equipping readers with the tools to innovate and lead in a dynamic and sustainable future.
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Veröffentlichungsjahr: 2025
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Table of Contents
Cover
Table of Contents
Title Page
Copyright Page
Preface
Part 1. Reaction Engineering
Chapter 1. Compaction, Compression and Consolidation in Pharmaceutical Industries
1.1. Introduction to compression, compaction and consolidation
1.2. Definition and importance in pharmaceutical manufacturing
1.3. Powder properties and their characterization
1.4. Powdered characterization techniques
1.5. Tablet compression, compaction process and consolidation mechanisms
1.6. Tablet properties and quality control
1.7. Tablet manufacturing challenges
1.8. Compaction data analysis
1.9. Conclusion
1.10. References
Chapter 2. Reactive Chromatography: A Concept of Multifunctional Reactors
2.1. Introduction
2.2. Concept of multifunctional reactor
2.3. Reactive distillation
2.4. Reactive chromatography
2.5. Types of chromatographic reactors
2.6. Comparative discussion
2.7. Applications of chromatographic reactors
2.8. Mathematical modeling of chromatographic reactors
2.9. Mathematical modeling of FBCRs
2.10. Equilibrium-based continuous models
2.11. General rate model and simplified versions
2.12. Phase distribution
2.13. Model parameters
2.14. Adsorption equilibrium isotherms
2.15. Challenges and future prospect of chromatographic reactors
2.16. References
Chapter 3. Mathematical Modeling of a Batch Reactor and a Non-Isothermal CSTR with Their Respective Simulation Using MATLAB and ASPEN PLUS
3.1. Introduction
3.2. Modeling of a batch reactor
3.3. Modeling of a non-isothermal CSTR
3.4. Conclusion
3.5. References
Part 2. Material Properties and Advanced Applications
Chapter 4. Properties of Materials and Selection Criteria
4.1. Introduction
4.2. Mechanical properties
4.3. Chemical properties
4.4. Other significant properties
4.5. Criteria for material selection with design consideration
4.6. References
Chapter 5. Hydrogen Production Pathways and Role of Catalysts
5.1. Introduction
5.2. Hydrogen production mechanisms
5.3. Renewable production methods
5.4. Conventional and membrane reformers
5.5. Catalysts for hydrogen production technologies
5.6. Conclusion and future prospects
5.7. References
Chapter 6. Maximizing Vinyl Chloride Production: An ASPEN PLUS Simulation Approach
6.1. Introduction
6.2. Methodology
6.3. Results and discussion
6.4. Energy used
6.5. Conclusion
6.6. References
Chapter 7. Process Intensification and Advanced Materials
7.1. Introduction
7.2. Process intensification technologies
7.3. Integration of process intensification and advanced materials
7.4. Conclusion and future prospects
7.5. References
Chapter 8. Nanotechnology in Chemical Engineering
8.1. Introduction to nanotechnology
8.2. Role of nanotechnology in chemical engineering
8.3. Emerging trends in nanotechnology-based chemical engineering
8.4. Challenges and solutions in nanotechnology for chemical engineers
8.5. Impact of nanotechnology on the future of chemical engineering
8.6. Case studies on the application of nanotechnology in chemical engineering
8.7. Future prospects of nanotechnology in chemical engineering
8.8. Conclusion
8.9. References
Part 3. Sustainability and Safety
Chapter 9. Green Chemistry and Sustainable Processes
9.1. Introduction
9.2. The principles of green chemistry
9.3. Applications of green chemistry
9.4. Challenges and barriers
9.5. Sustainable processes
9.6. Case study: green chemistry in the textile industry
9.7. Conclusion
9.8. Acknowledgments
9.9. References
Chapter 10. Waste Minimization and Resource Recovery
10.1. Introduction
10.2. Types of wastes and various waste minimization techniques
10.3. Advantages of waste minimization
10.4. Process enhancement through waste minimization in chemical engineering
10.5. Resource recovery as an efficient way to minimize waste
10.6. Sustaining waste minimization
10.7. References
Chapter 11. Safety Management: Hazard Identification and Risk Assessment at the Workplace
11.1. Introduction
11.2. Hazard identification
11.3. Process hazards checklist
11.4. Hazard survey
11.5. Hazards and operability (HAZOP) studies
11.6. Safety review
11.7. Other methods
11.8. Risk assessment
11.9. Quantitative risk analysis
11.10. Conclusion
11.11. References
List of Authors
Index
Summary of Volume 1
Other titles from iSTE in Chemical Engineering
End User License Agreement
List of Tables
Chapter 1
Table 1.1.
Angle of repose versus flow behavior
Table 1.2.
Compressibility index versus flow behavior
Chapter 2
Table 2.1.
Some important applications of RC for liquid–solid systems
Chapter 4
Table 4.1.
Various insulating materials (ASTM 2023)
Table 4.2.
Cost comparison for steel
Table 4.3.
Metals and their usages
Chapter 5
Table 5.1.
Catalysts used for methanol steam reforming
Chapter 6
Table 6.1.
Result of dichloroethane after heater 2 from ethylene feedstock
Table 6.2.
Result of dichloroethane after the reaction at SREACT 2 from et...
Table 6.3.
Result of column 1 light key HCL from ethylene feedstock
Table 6.4.
Production of vinyl chloride from the process plant from ethylene...
Table 6.5.
Conversion of acetylene and HCl in acetylene feedstock vinyl ch...
Table 6.6.
Production of vinyl chloride from the acetylene feedstock
Chapter 7
Table 7.1.
Selected definitions from the last 25 years concerning process...
Table 7.2.
Advantages of process intensification
Table 7.3.
Disadvantages of process intensification
Chapter 11
Table 11.1.
Selected data on various chemical compounds for the Dow F&EI
Table 11.2.
Degree of hazard measured by Dow F&EI
List of Figures
Chapter 1
Figure 1.1.
Different types of mechanisms involved in consolidation (prepared...
Figure 1.2.
Derived properties of powder (prepared for this work)
Figure 1.3.
Types of voids (prepared for this work)
Figure 1.4.
Compressibility and compactability (prepared for this work)
Figure 1.5.
Steps involved in the compression process (prepared for this work)
Figure 1.6.
Steps involved in the compression of the tablet (prepared for...
Figure 1.7.
Plot of porosity versus log of compression force (prepared for...
Figure 1.8.
Plot of specific surface area versus compression force (prepar...
Figure 1.9.
Plot of disintegration time versus log of compression force...
Figure 1.10.
Problems arise in the tableting process (prepared for this...
Figure 1.11.
Heckle plot for type A, type B and type C materials (prepar...
Chapter 2
Figure 2.1.
Standard distillation configuration (left) and the reactive...
Figure 2.2.
Classification of chromatographic reactors (prepared in this w...
Figure 2.3.
FBCR working principle (pulse mode) for a reversible reaction...
Figure 2.4.
Working principle of RFCR for the reversible reaction A...
Figure 2.5.
TMBR working principle for a reversible reaction (Acetic...
Figure 2.6.
SMBR working principle for a reversible reaction (Acetic...
Figure 2.7.
Schematic of centrifugal partition chromatographic reactor (CP...
Figure 2.8.
Schematic of centrifugal partition chromatographic reactor (CP...
Figure 2.9.
Schematic of Hashimoto chromatographic reactor (HCR) (prepared...
Figure 2.10.
Differential volume element of a column (prepared in this work).
Chapter 3
Figure 3.1.
Variation of concentration with respect to time (prepared for...
Figure 3.2.
Process block diagram of batch reactor simulated using ASPEN...
Figure 3.3.
Process flow diagram of batch reactor simulated using ASPEN PL...
Figure 3.4.
Variation of concentration with respect to time (prepared for...
Figure 3.5.
Variation of temperature with respect to time (prepared for...
Figure 3.6.
Variation of enthalpy with respect to time (prepared for this...
Figure 3.7.
Process block diagram of CSTR simulated using ASPEN PLUS (prep...
Figure 3.8.
Process flow diagram of CSTR simulated using ASPEN PLUS (prepa...
Chapter 4
Figure 4.1.
Engineering stress–engineering strain curve (Tu et al. ...
Figure 4.2.
Comparison of several hardness scales (Tubing China 2023) ...
Chapter 5
Figure 5.1.
Conventional reformer versus membrane reformer technology for...
Figure 5.2.
Possible products of glycerol
Figure 5.3.
Water electrolysis.
Figure 5.4.
Qualitative percentage distribution for different catalysts...
Chapter 6
Figure 6.1.
Flowsheet of vinyl chloride from ethylene feedstock (prepared...
Figure 6.2.
Process of vinyl chloride production by using an acetylene fee...
Figure 6.3.
Graph showing the actual and target cost to produce vinyl chlo...
Chapter 7
Figure 7.1.
Advanced material for process intensification (figure complied...
Figure 7.2.
Process intensification of distillation column (open access:...
Figure 7.3.
Conventional production of biodiesel using CSTR (figure compli...
Figure 7.4.
Supercritical fluid extraction unit (source: NPTEL).
Chapter 8
Figure 8.1.
Nanotechnology in various interdisciplinary applications.
Figure 8.2.
General features and functions of nanosystems.
Figure 8.3.
Nanotechnology in targeted drug delivery systems.
Chapter 9
Figure 9.1.
Principle of green chemistry.
Chapter 11
Figure 11.1.
Hazard identification and risk assessment process flow (prepa...
Figure 11.2.
Process for determining risk analysis data, including the fir...
Figure 11.3.
Steps involved in the implementation of the DOW chemical expo...
Figure 11.4.
Overview of risk (prepared for this work).
Figure 11.5.
A layer of protection to reduce the likelihood of a particula...
Guide
Cover Page
Table of Contents
Title Page
Copyright Page
Preface
Begin Reading
Conclusion
Index
Summary of Volume 1
Other titles from iSTE in Chemical Engineering
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Chemical Engineering Essentials 2
Advanced Processes, Materials, and Sustainability
Edited by
Raj Kumar Arya
George D. Verros
J. Paulo Davim
First published 2025 in Great Britain and the United States by ISTE Ltd and John Wiley & Sons, Inc.
Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms and licenses issued by the CLA. Enquiries concerning reproduction outside these terms should be sent to the publishers at the undermentioned address:
ISTE Ltd27-37 St George’s RoadLondon SW19 4EUUKwww.iste.co.uk
John Wiley & Sons, Inc.111 River StreetHoboken, NJ 07030USAwww.wiley.com
© ISTE Ltd 2025The rights of Raj Kumar Arya, George D. Verros and J. Paulo Davim to be identified as the authors of this work have been asserted by them in accordance with the Copyright, Designs and Patents Act 1988.
Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s), contributor(s) or editor(s) and do not necessarily reflect the views of ISTE Group.
Library of Congress Control Number: 2024951537
British Library Cataloguing-in-Publication DataA CIP record for this book is available from the British LibraryISBN 978-1-83669-017-7
Preface
The field of chemical engineering has evolved significantly over the decades, expanding its horizons to encompass a range of interdisciplinary applications and cutting-edge advancements. Chemical Engineering Essentials 2 is designed as a comprehensive resource for both students and professionals, providing fundamental insights along with in-depth discussions on advanced topics. With the rapid advancements in technology and growing concerns over sustainability and safety, chemical engineering is at a transformative juncture, poised to offer sustainable and innovative solutions across industries. This handbook seeks to serve as a definitive guide for the current generation of engineers, providing both foundational knowledge and modern approaches required to navigate and excel in this dynamic field.
Volume 2 is organized into three sections, as is Volume 1, each addressing critical aspects of chemical engineering.
Part 1 of Volume 1: Fundamental Principles lays the groundwork, beginning with an overview of the field and covering essential topics like material and energy balances, thermodynamics and phase equilibrium. These fundamental principles form the bedrock upon which more specialized knowledge is built, equipping readers with a strong theoretical base.
Part 2 of Volume 1: Fluid Mechanics and Transport Phenomena delves into the physics and behavior of fluid systems and heat transfer. Chapters on fluid flow, heat conduction, convection, radiation and mass transfer provide essential understanding for designing and analyzing chemical processes.
Part 3 of Volume 1: Separation Processes covers the vital area of chemical separations, with discussions on extraction, distillation, filtration and emerging membrane processes such as pervaporation. Mathematical modeling techniques for binary and multicomponent distillation are also covered to provide a deeper insight into process design and optimization.
Part 1 of this volume: Reaction Engineering introduces readers to various reaction mechanisms and reactor designs, with a special focus on applications within the pharmaceutical industry and the concept of reactive chromatography. The section concludes with the mathematical modeling of batch reactors and non-isothermal continuous stirred-tank reactors (CSTRs), complemented by simulation studies using MATLAB and ASPEN PLUS.
Part 2 of this volume: Material Properties and Advanced Applications focuses on the diverse materials used in chemical engineering, alongside advanced applications like hydrogen production, vinyl chloride production, process intensification and the integration of nanotechnology in the field. These topics underscore the importance of selecting the right materials and processes to achieve efficiency and innovation in chemical engineering applications.
Part 3 of this volume: Sustainability and Safety highlights the importance of green chemistry and sustainable practices in chemical engineering. This section also covers waste minimization, resource recovery and safety management, including hazard identification and risk assessment, which are critical components of responsible engineering practice in today’s world.
This handbook represents the collective effort of numerous contributors, whose expertise and dedication have shaped this comprehensive guide. We extend our deepest gratitude to each author who has contributed invaluable insights and research to make this work possible. Our heartfelt thanks also go to our families, whose unwavering support, love and encouragement made this journey possible.
Special acknowledgment goes to the team at ISTE. Their efforts and guidance were instrumental in bringing this book to completion.
It is our sincere hope that Chemical Engineering Essentials 1 and 2 will serve as valuable resources, offering knowledge, inspiration and practical tools for all of those engaged in the field of chemical engineering.
Raj Kumar ARYA
George D. VERROS
J. Paulo DAVIM
January 2025
PART 1Reaction Engineering
1Compaction, Compression and Consolidation in Pharmaceutical Industries
Compressibility and compactability are the defining features of medicinal powder’s compaction characteristics. The capacity to create mechanically robust compacts is known as compactability, whereas compressibility refers to the powder’s deformability under pressure. Compaction, in the context of pharmaceutical powders, involves the combined processes of compression and consolidation between the solid particles and gaseous phase, caused by an external force. This is relevant to pharmaceutical powders, particularly processes such as the handling of powdered pharmaceuticals, hard shell gelatin capsule filling, tablet and granule manufacturing, and other processes in the field of pharmaceuticals which are especially vulnerable to the impacts of such forces. Studying the possibilities that occur during the compaction of pharmacological materials is the crucial aspect of designing solid dosage forms, whereas universal testing machines or compaction simulators make systematic investigations of pharmaceuticals easier (Nguyen et al. 2020). Various parameters are measured during compaction among various researchers. Several pharmaceutical powders and formulations have had their compaction behavior evaluated using data collected from various measurements, including punch forces, die wall friction, ejection forces, change in temperature during compaction and other random variables. Among all other mathematical models, Heckel and Kawakita models show a better mathematical representation of compaction for the pharmaceutical systems within the appropriate pressure range.
1.1. Introduction to compression, compaction and consolidation
The matter or the substances present in the form of powdered solids are heterogeneous. They consist of various individual particles with different shapes and sizes in the presence of air voids. This is why it is difficult to analyze and characterize the fundamental properties of this complex powdered solid system (Lachman et al. 1986). However, with the considerable advancements in qualitative and quantitative measurements, it is possible to determine some fundamental properties of individual particles as well as bulk powdered solids from an industrial point of view. In pharmaceutical industries, the study of the physical and mechanical properties of powdered solids is necessary for the compression, compaction and consolidation of tablets.
1.2. Definition and importance in pharmaceutical manufacturing
1.2.1. Compression
Compression is the mechanical process of reduction of bulk powdered solid under applied pressure resulting in the removal of air spaces or voids. In pharmaceutical industries, compression is used for the tableting process of a particular volume of granules in a die cavity under pressure to convert it into an intact tablet. An appropriate volume of powdered solid is taken in a die cavity/mold that is compressed under pressure using an upper and a lower punch to convert it into a single matrix by removing air/gas voids, then ejected from the die/mold in the form of a tablet (Dudhat 2022).
The assessment of the compression behavior of a powdered solid is mainly dependent upon the macroscopic properties, i.e. density of solid bed and porosity. Furthermore, these properties are also affected by the punching velocity of compression, stress–strain indices and elasticity of the material after compression (Vanhoorne and Vervaet 2020).
1.2.2. Compaction
Compaction of a powdered solid is defined as the ability of powdered solid compressed to form a coherent compact solid tablet having high mechanical strength under increasing stress (Stranzinger et al. 2021; Dudhat 2022).
Compaction is considered to be one of the most important pharmaceutical unit operations. For good compaction of tablets, powdered solids must have excellent flowability and a lesser tendency of segregation. The mechanical strength of a compact solid depends upon the physical, chemical and mechanical properties of the constituent solid such as hardness, flowability, particle–particle interaction, etc., whereas lubricants and moisture content also affect the compactability of the material (Bellini 2018).
Compaction = Compression + Consolidation of two phases (solid + gas) on applying force
1.2.3. Consolidation
Consolidation is the state of powdered solid having mechanical strength due to particle–particle interactions (Mohan 2012).
There are mainly three types of mechanisms involved in the consolidation of powder solids:
cold welding;
fusion welding;
recrystallization.
Figure 1.1.Different types of mechanisms involved in consolidation (prepared for this work)
1.2.3.1. Cold welding
Cold welding is one of the most widely used mechanisms for consolidation when the surface of two particles lies close enough to each other (i.e. less than 50 nm distance) having a strong attractive force, leading to strong particle–particle interaction. For this reason, cold welding increases the mechanical strength of powdered solid bed, when high compressive forces are applied.
1.2.3.2. Fusion welding
Generally, pharmaceutical powdered solids have irregular shapes and sizes, which provide a large surface area of contact (Mori et al. 2020). Therefore, a small compression force is sufficient to increase the particle–particle area of contact (Mohan 2012). If a high compression force is applied through the powdered solid bed, a considerable amount of frictional heat is produced. This heat is dissipated through the contact surfaces of solid, which causes melting of the contact area of solid particles (Sampat et al. 2022). Fusion occurs at the contact surface after the melting of irregular shapes or corners of solid particles. Melt solidifies on the removal of compressive load, which leads to a further increase in the mechanical strength of the solid bed, known as fusion bonding. There must be a possibility of deformation of the solid surface, causing the breaking and formation of new bonds, which in turn increases the consolidation effect (Wahlich 2021).
1.2.3.3. Recrystallization
The solubility of a powdered solid is directly proportional to the applied compression load. If a high compression load is applied at the point of contact of moisture and solid surface, the solubility of the solid in solution also increases.
1.2.4. Factors affecting consolidation process
1.2.4.1. Chemical properties of solids
The lattice structure and nature of the crystallinity of the powdered solid affected the solidity of the material under high compression loads (Fonteyne et al. 2015). For example, those particles having cubic lattice structures are more suitable for the tableting process than those having rhombohedral lattices.
1.2.4.2. Extent of availability of surface
The consolidation of a powdered solid is also dependent upon the extent of availability of specific surface area. When compressive force is increased to an appreciable extent, particle surfaces become fractured, which leads to an increase in surface area. Further increase in compressive force causes particles to rebond. Hence, at very high compressive force, the surface area decreases to form a solid bed of powdered solid called tablet lamination.
1.2.4.3. Effect of the presence of contamination on the surface of the particle
The consolidation process is also affected due to the presence of surface contaminants. Surface contamination plays a vital role in the initial bond formation between powdered solid particles. For example, the presence of diluents, and lubricants on the surface of pharmaceutical powder aims to create a weak bond between them. This causes continuous coating on the tableting mass. Therefore, if contamination occurs at a larger extent on the surface of particles, it results in the formation of weaker tablets (Arshad et al. 2021).
1.2.4.4. Interparticle attractive forces
The interparticle attractive forces have a direct influence on the consolidation of the powdered solid bed. When a small compressive load is applied, molecular or electrostatic forces exist between individual particles. Van der Waals forces become predominant at an intersurface distance of 100 nm, which tends to form agglomerates. This agglomeration leads to an increase in the air spaces of the solid bed. The tablet then formed has low mechanical strength and is not stabilized. This may lead to cracking in the internal structure.
Therefore, the consolidation behavior of powdered solid can be controlled by internal (Van der Waals) as well as external forces (i.e. elasticity and plasticity). Consolidation gives rise to a decrease in air space, hence preventing the breakdown of a tablet (Kengar et al. 2019).
1.3. Powder properties and their characterization
1.3.1. Characteristics of pharmaceutical powders, flowability, particle size and distribution
Figure 1.2.Derived properties of powder (prepared for this work)
While considering the tableting process of the pharmaceutical powdered solid, some physical and mechanical properties of solid particles play a key role, which further affects the compressibility, compactability and consolidation behaviors of powder (Awad et al. 2021).
Some of the most important physical properties are density, porosity, particle size, shape and distribution, and moisture content. These physical properties help us to understand the flow behavior of the powdered solid, and a change in one such property may affect the other, resulting in a change in the compression and consolidation behavior of tablets. Physical properties are also related to the study of dosage form as well as the bioavailability of the tablet.
On the other hand, the mechanical properties of powder deal with the compression–decompression behavior or stress–strain behavior.
1.3.1.1. Volume
The mass of the bulk powdered solid can be measured easily as compared to the measurement of the volume of powder. When a powdered solid is poured into a container under gravity, the air spaces or voids must be present there. That is why more complications arise while measuring the actual volume of the powdered solid. These air voids are mainly of three types and are explained using mass–volume relationships:
Open intraparticulate voids
: these voids are present within a single particle of powdered solid but are open to the external environment.
Closed intraparticulate voids
: the voids lie within the single particle but are closed to the external environment.
Interparticulate voids
: the air voids that exist between the individual particles of powdered solid.
Figure 1.3.Types of voids (prepared for this work)
In keeping these air voids under consideration, the powdered volume can be classified as follows:
True volume (V
T
)
: true volume of powdered solid can be defined as the total volume of the solid particulate itself except the volume occupied by the inter- and intraparticulate voids.
Granular volume (V
G
)
: the granular volume of powdered solid is the sum of the volume occupied by the solid particulate itself and the volume occupied by all intraparticulate voids (except interparticulate voids)
Bulk volume (V
B
)
: the bulk volume of powdered solid is equal to the sum of the volume occupied by the solid particulate itself, intraparticulate voids as well as interparticulate voids
or
Relative volume (V
R
)
: relative volume can be defined as the ratio of the experimental volume of sample (V
E
) under specific conditions of the experiment to the true volume (V
T
) of the powdered solid sample, i.e.
Relative volume tends to approach unity if the experimental volume of the sample (VE) becomes equal to the true volume (VT), i.e. under compressive force, all of the air voids will be eliminated from the particular packing of the powdered solid.
1.3.1.2. Density
The density (ρ) of the powdered solid is defined as the ratio of the mass of the solid to the volume occupied by the solid
Based on the three types of volumes discussed above, the density of the powder is also classified as the following:
True density (ρ
T
)
: this is the ratio of the mass of the powder to the true volume of the powder
Granular density (ρ
G
)
: this is the ratio of the mass of the powder to the true volume of the powder
Bulk density (ρ
B
)
: this is the ratio of the mass of the bulk powder to the bulk volume of powder, especially when a particular mass of the powdered solid is poured into a cylinder with flow under gravity
Relative density (ρ
R
)
: if ρ is the density of the sample under specific experimental conditions and ρ
T
is the true density, and then the relative density is defined as the ratio of ρ/ρ
T
The relative density tends to unity if ρ = ρT when all of the air spaces or voids are eliminated from the particular packing of the powdered solid.
1.3.1.3. Porosity (ε)
The air voids present in powdered solid packing are of more importance as compared to the solid mass (Dudhat 2022). Therefore, the porosity of the powdered solid is the ratio of the total volume occupied by the air voids (VV) to the bulk volume of the powdered solid (VB)
The total volume occupied by the air voids (VV) is also given by the difference in the bulk volume and true volume of the powdered solid,
On equating equations [1.7] and [1.8], we get
The percentage porosity is given by
Porosity is an important factor while studying the compression behavior of tablets, which helps to determine the disintegration time, dissolution rate, friability and drug absorption mechanism.
1.3.1.4. Flow properties
In the tableting process, when pharmaceutical powder is poured into the die to make a compact tablet, it is required that the powdered solid have good or excellent flow properties so that the die should be filled properly during compression and the tablet formed has enough mechanical strength (Mohan 2012). The flow behavior depends upon the following factors.
1.3.1.4.1. Particle size
The rate of flow of the powdered solid is directly proportional to the size of the particles. The particles having small diameters cohere with each other due to van der Waal’s forces, electrostatic attraction and surface tension. These attractive forces result in poor flow behavior of particles, whereas particles with large diameters decrease the cohesion of particles, which enhances the flow property due to the lesser influence of gravitational force.
1.3.1.4.2. Particle shape
Those particles having spherical shapes with smooth surfaces of contact show good flow behavior as compared to the needle type or elongated particles with rough surfaces. The roughness of the surface tends to increase the friction factor and cohesiveness of the particles, which leads to poor flow behavior of powdered solids.
1.3.1.4.3. Porosity and density
As discussed above, density and porosity are two important physical properties of powdered solids. High-density particles have a large mass-by-volume ratio, which leads to good flow behavior, whereas large porosity decreases the flow characteristic of particles.
1.3.1.4.4. Moisture content
Powdered solid containing high moisture content has large cohesion and adhesion properties. When particles get stuck to each other, they cause poor powder flow properties. Therefore, dry mass enhances the flow properties of the powdered solid.
1.4. Powdered characterization techniques
1.4.1. Determining flow properties and compressibility
There are two main parameters to measure the flow behavior of pharmaceutical powdered solid, i.e. angle of repose and compressibility factor/compressibility index (Garg et al. 2018).
1.4.1.1. Angle of repose
The angle of repose is one of the simplest methods to determine the flow behavior of powdered solids. It is that the critical angle (θ) at which the powdered solid forms a conical heap relative to the horizontal base when it is allowed to fall through the funnel under gravity onto the horizontal surface
where:
h
= height of the heap of the powdered solid;
D
= diameter of the heap base;
r
= radius of the heap base;
θ
= angle of repose.
Table 1.1.Angle of repose versus flow behavior
S. No.
Angle of repose (in degree)
Type of flow
1
25–30
Excellent
2
31–35
Good
3
36–40
Fair
4
41–45
Passable
5
46–55
Poor
6
56–65
Very poor
7
More than 66
Poorest
Therefore, the angle of repose of the pharmaceutical powder can be determined by measuring the height and base diameter or radius of the heap formed by the powdered solid when it falls through the funnel under gravity. The greater the angle of repose, the better the flow ability will be. Table 1.1 gives the relationship between the angle of repose and the flow behavior.
Fine, cohesive or sticky materials have a larger angle of repose. Therefore, it has been observed that the angle of repose increases with an increased moisture content due to the formation of aggregates.
1.4.1.2. Compressibility factor/compressibility index (I)
The compressibility index is also helpful in determining the flow behavior of powdered solids. The compressibility index is the measure of the decrease in volume of matter when placed under pressure. When pressure is applied on the bed of powdered solid, the volume of powder decreases until all of the air voids or spaces are removed.
The compressibility factor can be measured by pouring the powdered solid into a measuring cylinder without any disturbance. The volume occupied by the undisturbed powder (VO) and compressed powder (V) (i.e. after applying external force when there is no air void or space between the particles of powder) will be noted down and used to determine the compressibility index/compressibility factor (I)
where:
V
= volume occupied by the powdered solid after compression;
V
O
= volume occupied by the undisturbed powdered solid before compression.
Table 1.2.Compressibility index versus flow behavior
S. no.
Compressibility index
Type of flow
1
≤ 10
Excellent
2
11–15
Good
3
16–20
Fair
4
21–25
Passable
5
26–31
Poor
6
32–37
Very poor
7
>38
Poorest
Therefore, the compressibility index can be defined as the ratio of the decrease in the volume of powder after applying pressure to that of the undisturbed volume of powder solid.
Percentage compressibility can be determined as
Table 1.2 represents the values of the compressibility index relative to the particular type of flow behavior of the powdered solid.
1.4.2. Determination of tapped density and bulk density
The compressibility index in terms of bulk density and tapped density is given by
Figure 1.4.Compressibility and compactability (prepared for this work)
1.5. Tablet compression, compaction process and consolidation mechanisms
1.5.1. Steps involved in the compression process, mechanisms and principles
Figure 1.5.Steps involved in the compression process (prepared for this work)
1.5.1.1. Rearrangement/repacking of particles
When the tablet is formed from a powder solid, the main processes involved are the initial compression of the powdered solid to form a compact tablet leads to consolidation through various stages. Initially, when a powdered solid is compressed under a low compaction load, the small particles are shifted from their position and enter into the air voids present within the large particles in die packing. This gives rise to a closed packing arrangement, and leads to an increase in interparticulate friction as well as interparticulate surface area to increase the particle–particle interaction (Lachman et al. 1986; Mohan 2012). This initial packing of powder solid die cavity is mainly affected by the size and shape of particles. For example, spherically shaped particles are more suitable for tablet compression as compared to irregularly shaped particles (i.e. cubical, flat or needle-shaped particles) because spherical particles involve less rearrangement or repacking (Sahnen et al. 2020).
1.5.1.2. Reduction of volume
After the rearrangement or repacking of particles, the compaction load is increased to avoid further rearrangement. The extent of the reduction of the volume of pharmaceutical powder strictly depends upon the mechanical strength of particles as well as the mechanism involved in a reduction under pressure. At this stage, the final reduction of volume is attained followed by the deformation of particles at the surface of contact and fragmentation of particles.
1.5.1.3. Deformation of particles at contact surface
When the final reduction of volume is achieved, a further increase in stress does not affect the volume reduction of particle arrangement, as the packing arrangement has already become closed packed and no air void is present there. Hence, the filling of smaller particles into air voids within large particles no longer takes place. Therefore, an increase in compression force leads to the deformation of particles at the surface of contact.
Generally, the particles undergo two types of deformations, i.e. elastic deformation and plastic deformation. The deformation of particles is also dependent on the physical and mechanical properties of the material. Besides this, the amount of applied compression load is also considered.
When a powdered solid bed is enclosed in a die bearing the load of external forces of upper and lower punch, it gives rise to the deformation of particles. After reaching a critical point of deformation, the applied compressive load is removed. Therefore, particles are either deformed elastically, i.e. the particles return to the original shape on the release of stress or the particles deformed plastically, i.e. the particles will remain in their deformed state even after the removal of stress. This plastic deformation of particles leads to the compaction of a tablet.
1.5.1.4. Fragmentation and deformation
Under the applied stress, particles of powdered solid are not only deformed elastically or plastically, there must be a possibility of fragmentation, and deformation occurs. Fragmentation does not occur if particles are plastically deformed on the removal of stress. If particles undergo elastic deformation, fragmentation occurs under high pressure which results in fractures or cracks on the surface of particles to form new surfaces for bonding (Mohan 2012). Excessive fragmentation occurs in the case of brittle and highly porous material. Hence, more bonding sites will be available, whereas ductile materials that have a low porosity do not undergo fragmentation.
1.5.1.5. Bonding
After fragmentation, further increases in pressure cause the formation of new bonds between the available surface sites of particles, increasing the mechanical strength of the powder bed under large compressive force. The bonding can be explained using the following theories.
Mechanical theory
: the true volume of the powdered solid can be defined as the total volume of the solid particulate itself except the volume occupied by the inter- and intraparticulate voids.
Intermolecular theory
: according to this theory, at this stage bonding between new contact surfaces of particles is only due to the van der Waals forces, because the contact surfaces lie close enough to each other (i.e. 100 nm distance) under high pressure to consolidate the particles.
Liquid surface film theory
: this theory deals with the bonding of particles in the presence of liquid thin film, which may result from melting or fusion welding. The necessary condition for this type of bonding is the solubility of the solid material.
1.5.1.6. Deformation of solid bonding
As the pressure increases, the strength of the consolidated solid increases followed by a decrease in the density of solid packing within the die cavity.
1.5.1.7. Decompression
At this stage of decompression, all kinds of stress or compressive forces are removed for the compaction and consolidation of the tablet. Furthermore, some of the factors must be kept in mind while the tablet is unloaded from the die. As quick loading or unloading of solid bed, brittle fracture, and further plastic deformation may occur. Two main steps have to be considered before studying the decompression process.
1.5.1.7.1. Pre-compression
In the pharmaceutical tableting process, pre-compression is the stage when a small compressive force is applied for the partial formation of the tablet. Compressive forces are further increased slowly in multistage to get better hardness of tablet, especially in the case of brittle and porous material.
1.5.1.7.2. Main compression
Under main compression, there is a formation of interparticulate bonds within the interparticulate contact surface. Initially, particles are rearranged to a more dense structure. Furthermore, an increase in applied force results in fragmentation or deformation of particles.
Figure 1.6.Steps involved in the compression of the tablet (prepared for this work)
On removal of applied pressure, in the die cavity, elastic deformation occurs on the contact surfaces of the tablet due to elastic recovery. To handle this stress, the tablet must have high mechanical strength. Otherwise, it may result in the fracture of the tablet. If the tablet is more elastic, then capping or lamination may occur. Tablets that undergo plastic deformation are strong enough to hold this stress and do not undergo capping or lamination on decompression. The failure or fracturing of the structure is also influenced by the speed of the process (Mohan 2012).
1.5.1.8. Ejection
The last step involved in the compression of the tablet is the ejection of the tablet from the die cavity. In this process, the ejection force of the lower punch must be enough to overcome the adhesion between the die wall and the compact surface of the tablet. Lubricants may help to minimize the effect of the die wall and tablet adhesion, hence reducing the necessity of capping or lamination of material by increasing the tendency of cohesiveness.
1.6. Tablet properties and quality control
1.6.1. Properties of tablet influenced by compression
1.6.1.1. Density and porosity
As the compressive force increases, the particles of powdered solid beds tend to achieve a limiting density of material. Therefore, an increase in the compressive force increases the density of the tablet. Porosity is inversely proportional to the density of the tablet. The plot shows the relation between porosity and the log of compressive force. As the compressive force increases, particles of solid bed come close to each other to make the material less porous; hence, the porosity decreases (Markl et al. 2018; Wilms et al. 2020). The relation between porosity and density of the tablet is given by
Figure 1.7.Plot of porosity versus log of compression force (prepared for this work)
1.6.1.2. Hardness and tensile strength
As the compressive force increases, fragmentation and deformation of granules occur, which leads to an increase in specific surface area. Figure 1.8 shows the general behavior of the material with an increase in compressive force. With the increase in specific surface area, there is more availability of sites for bonding. Hence, the hardness and tensile strength of the tablet show a linear relationship with compressive force. Furthermore, an increase in pressure or compressive force may decrease the surface area due to the formation of interparticle bonding.
Figure 1.8.Plot of specific surface area versus compression force (prepared for this work)
1.6.1.3. Disintegration time
Generally, as the applied compressive force increases, the hardness and tensile strength of the tablet also increase, which further increases the disintegration time of the tablet. The case may be different for porous or less dense particles. Exception is also there for coated or non-coated tablets.
Figure 1.9.Plot of disintegration time versus log of compression force (prepared for this work)
1.6.1.4. Dissolution rate
As compared to the disintegration time of the tablet, the dissolution rate of the tablet is difficult to predict along with a change in applied compressive force. In the case of a non-coated tablet, the properties of API and excipients also affect the dissolution rate. But generally, if fragmentation occurs while compaction of the tablet, the increase in specific surface area increases the bonding of particles, hence decreasing the dissolution rate of the tablet.
1.6.2. Factors affecting the strength of the tablet
1.6.2.1. Crushing strength of tablet
Crushing strength (ST) can be determined easily by applying compressive force (Fc) on the tablet along its diameter until it fractures. It is given by the relation
ST is the tensile strength, Fc is the compression force, and D and H are the diameter and thickness of the tablet, respectively.
1.6.2.2. Friability
Friability is another parameter to measure the potential and mechanical behavior of tablets while packaging. The friability test measures the weight loss of tablets by revolving the tablets in a standardized plastic wheel at 25 rpm. Compressed tablets having a weight loss of more than 0.5–1.0% of the tablet weight can be acceptable for packaging
where:
w
1
is the initial weight of the tablet before the test;
w
2
is the final weight of the tablet after the test.
1.6.2.3. Particle size and shape
Under compression, large particles become fragmented into smaller ones, provide a large number of interparticle contact surfaces and tend to have large bonding sites. Particle shape is also an important factor. For example, spherical particles have good flow properties, whereas cubical or irregularly shaped particles have poor flowability.
1.6.2.4. Binder and lubricants
Binders improve the mechanical strength of the tablet during compression, whereas the process becomes reversible during the decompression of the tablet.
Lubricants improve the flow behavior of particles and minimize the die wall friction which helps to prevent the adhesion of particles.
1.6.2.5. Thickness test
Thickness is also affected by changing the applied compressive force. Tablet thickness can be determined using an vernier caliper, which further influences the packaging of the tablet. The variation in the tablet diameter should be within ± 5% variation.
1.6.2.6. Weight variation
Uneven distribution of the pharmaceutical powdered solid in the die cavity may result in weight variation of tablets. It can be done by weighing 20 tablets individually, then the average weight of 20 tablets is compared with the individual tablet weight and is given by the relation
where:
IW
= individual weight;
AW
= average weight.
1.7. Tablet manufacturing challenges
1.7.1. Capping, lamination and sticking issues
The main issues that arise during the tableting process under compression force are capping, lamination, sticking and picking (Mohan 2012; Takeuchi et al. 2020). Capping and lamination problem mainly arises during the pre-compression and main compression processes.
1.7.1.1. Capping
This problem arises when the upper and lower layers of the tablet separate completely or partially from the main body during ejection from the die wall cavity called capping. The presence of large amounts of fines, low moisture content, and insufficient binders and lubricants cause capping in the tableting process.
1.7.1.2. Lamination
When the compression force is rapidly applied and removed on ejection of the tablet from the die, the tablet is separated into two different horizontal layers called lamination of the tablet.
This type of effect is shown by those materials having a high content of oily granules and hydrophobic lubricants.
1.7.1.3. Sticking
Sticking may occur, while the ejection of the tablet can be defined as the tablet material, which adheres to the die wall. The granules or particles have moisture content, lesser lubricant, too many binders and soft materials associated with this effect. A rough die wall and too deep a die cavity with rapid compression also affected the sticking of the tablet.
1.7.1.4. Picking
Picking refers to the tablet surface material adhesion, only related to the letter, logos or design embossed on the punch faces. The pharmaceutical powder having low melting becomes soft due to the heat of compression. Moisture level is one of the most important factors affecting the picking and sticking process.
Figure 1.10.Problems arise in the tableting process (prepared for this work)
1.7.2. Solutions and troubleshooting
The amount of constituents of the pharmaceutical drugs such as API, excipients, diluents, lubricants binders, etc., in the tablet must be considered for the troubleshooting of tableting issues (Mohan 2012).
1.7.2.1. API modification
In high-dose drugs, excipients are present in lesser amounts. Therefore, API modification helps to improve the quality of tablets.
1.7.2.2. Excipient selection and modification
The amount of excipients present in a tablet is mainly associated with the overall quality of the tablet. Excipients such as diluents and binders have positive effects, whereas disintegrants and lubricants have negative effects on the compaction of tablets.
1.7.2.3. Diluents
Diluents are the fillers that help to increase the bulk volume of the tablet. Therefore, diluents improve the cohesion of particles, flow behavior, and direct compression can be applied, for example lactose and mannitol.
1.7.2.4. Lubricants
Lubricants help to decrease the friction at the interface of the tablet and die wall during ejection. They also prevent the stickiness of tablet surfaces with punch surfaces and enhance the flow behavior of material by reducing interparticulate friction. Examples of some lubricants are magnesium stearate, calcium stearate and polyethylene glycol.
1.7.2.5. Binders
Binders are also known as granulating agents because the addition of binders in the formation of a tablet improves the mechanical or granular strength of the tablet. Water and organic solvents can be used as a binder to form granules from powdered solids. They are cohesive and are important to minimize the problem of capping and lamination, for example, cellulose, methyl cellulose and sucrose.
1.7.2.6. Disintegrants
According to the need, some of the drug substances require the desired dissolution rate.
Therefore, disintegration helps to overcome through the cohesion of tablet particles and make the tablet break or disintegrate into primary particles. The main mechanism involved behind the disintegration of the tablet is to take up the moisture from the surroundings and make the tablet initially swallowed, decreasing its tensile strength. The addition of an optimum amount of disintegrants leads to poor compressibility of the tablet. The commonly used disintegrants are sodium starch glycolate and magnesium aluminum silicate.
1.8. Compaction data analysis
Several empirical relationships have been suggested to describe the data, which can be expressed in terms of stress–strain, pressure volume or pressure density. A compaction equation establishes a relationship between a certain characteristic of the powder’s consolidation state, such as volume, density, porosity and void ratio versus compaction pressure.
To show a better fit of experimental data to the model, the plot must be transformed into a linear form facilitating comparisons between different data sets. For the given wide range of pressures that can be examined in compaction studies, it is logical and appropriate to plot these pressures using a logarithmic scale. This allows for better visualization and differentiation of the data.
1.8.1. Heckel equation
The Heckel equation is derived from the premise that the compaction of the powder under force obeys first-order kinetics (Dudhat 2022). The Heckel equation is formulated as follows:
where D is the tablet’s relative density at any pressure P, K is the slope and A is the intercept.
A modified Heckel equation (Svačinová et al. 2022) is formulated by Kuentz and Leuenberger and is given as
where σ is pressure, ρ is the relative density, ρc is the critical density and C is constant. While Heckel plots can also be used for powder combinations, Mohan (2012) also reported that Hersey & Rees and York & Pilpel categorized powders into three distinct types: A, B and C. The categorization is determined by analyzing Heckel plots and evaluating the compaction behavior of the material.
While using type A materials, we observe a linear connection, where the graphs are parallel (Figure 1.11) as the applied pressure increases, which suggests that the deformation is primarily due to plastic deformation. Sodium chloride is an example of a substance that shows A type of behavior.
Typically, type A materials are soft, can easily deform plastically and have varying levels of porosity based on the packing in the die. This will further affect the size distribution as well as the shape of pharmaceutical powder material.
Type B materials exhibit an initial curved section followed by a linear segment (Figure 1.11), which suggests that the particles are undergoing fragmentation during the initial stages of compression. This may vary due to the brittle fracture of material before plastic flow. It is common for type B Heckel plots to be observed in materials that are more rigid and have greater yield pressures. These materials typically go through the process of compression by fragmentation first, which results in a denser packing with fewer voids. Lactose is a prime illustration of such substances.
A steep linear zone appears at the outset for type C materials (Figure 1.11), but it becomes overlaid and flattens down with increasing pressure. Densification is caused by plastic deformation, which is attributed to the lack of a rearrangement stage.
Furthermore, the compressive strength of tablets can be associated with the K values of the Heckel plot. Higher K values generally suggest tablets that are more resistant to crushing. This information can be used as a criterion for selecting binders for the formulation of tablets. Heckel plots can be affected by various factors, including the duration of compression, the amount of lubricant added as well as the dimensions of the die. Therefore, it is difficult to examine the impact of these variables on the compaction of tablets.
Figure 1.11.Heckle plot for type A, type B and type C materials (prepared for this work)
1.8.2. Kawakita’s equation
Kawakita’s equation for powder compression assumes that particles are compressed in equilibrium throughout the process (Dudhat 2022; Tishkov et al. 2022), resulting in a constant product of pressure and volume. The equation is given as
where Pa is the applied pressure axially, a and b are the constants determined from the slope and intercept of the plot, C is volume reduction, V is the compact volume at pressure Pa and Vo is the initial volume of powder. For low pressure and high porosity, this equation fits well with soft and fluffy medicinal powders.
1.9. Conclusion
Characterizing the compaction profiles of pharmaceutical materials necessitates familiarity with the principles underlying compatibility and compressibility. Both events play a significant role in the tablet formulation, whether a hard or soft compact is needed, as well as the brittleness of the materials will determine the relative relevance to depict the compaction process. Using a single equation is unlikely to be sufficient as different materials consolidate through various mechanisms based on their unique feature.
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