Manufacturing Chemical reactor and process technologies play a major role in a number of industrial sectors including pharmaceuticals, agrochemicals, paints and pigments, detergents, electronics and power generation – all of which matter to the global economy and quality of life. An enormous amount of effort has been made to improve existing reactor and process technologies, as well as to develop new ones, and as a result, the last few decades have seen significant progress in the area (1,2,3). Since then, however, concerns over energy and environmental issues have led to the birth of the so-called green chemical science and technology, and this has prompted engineers and scientists to take a fresh look at the field. Reactor and process technologies currently regarded as highly efficient and economically excellent may not be able to survive in the future. This forms the primary motivation for our programme at Leeds University’s Institute of Particle Science & Engineering to develop innovative reactor and process technologies. Over the past few decades, a concept called process intensification has gained popularity (4,5,6). Such a concept is often linked with green chemical science and technology, although in fact it came about much earlier in the 1970s when ICI (Imperial Chemical Industries, UK) invented the HiGee process. The concept has also been used in our reactor and process technology development. This article will summarise some of the most recent developments in the field, with a focus on systems involving particles. The article is structured in the following manner: first, a thermodynamic consideration will be made to illustrate that there is plenty of room for developing new and improved reactor and process technologies; this will be followed by a review of three examples of reactor and process developments; and finally, some concluding remarks will be made. THERMODYNAMIC CONSIDERATIONS For a chemical reaction or process, the endpoint is governed by the thermodynamic equilibrium, whereas the rate to reach the endpoint is determined by the reaction kinetics and transport phenomena (momentum, heat and mass transfer). As a consequence, the development of new and improved reactor and process technologies can be realised from the two aspects of thermodynamics and transport phenomena. The examples reviewed later will include both aspects. From the thermodynamic point of view, a chemical reaction or process involving more than one reaction can be viewed as reaching B (endpoint) from A (starting point) (see Figure 1). The first law of thermodynamics states that one can reach B from A if mass, momentum and energy conservation laws are satisfied. However, the second law of thermodynamics says that one may not be able to reach B even if these conservation laws are satisfied. In other words, the reaction or the process can only occur when the second law of thermodynamics is satisfied. The thermodynamic laws also imply that if the second law says that one can reach B from A, then there is an infinite number of routes between A and B. As a consequence, there is plenty of room for developing new or improved reactor and process technologies. The reactor and process technologies used today may be the best among the routes that have been explored, but they are by no means the best among all possible routes. The reactor and process technologies used today may be the best among the routes that have been explored, but they are by no means the best among all possible routes. Thermodynamic considerations show that there is plenty of scope for improving existing technologies as well as developing new ones. 82 Innovations in Pharmaceutical Technology By Yulong Ding at the Institute of Particle Science and Engineering, University of Leeds Novel Reactor and Process Technologies: Thinking Outside the Box Y X B A Figure 1: There are numerous routes between starting-point and end-point IPT 27 2008 4/12/08 11:11 Page 82
Transcript
Manufacturing
Chemical reactor and process technologies play a majorrole in a number of industrial sectors includingpharmaceuticals, agrochemicals, paints and pigments,detergents, electronics and power generation – all ofwhich matter to the global economy and quality of life.An enormous amount of effort has been made toimprove existing reactor and process technologies, as wellas to develop new ones, and as a result, the last fewdecades have seen significant progress in the area (1,2,3).
Since then, however, concerns over energy andenvironmental issues have led to the birth of the so-calledgreen chemical science and technology, and this hasprompted engineers and scientists to take a fresh look atthe field. Reactor and process technologies currentlyregarded as highly efficient and economically excellentmay not be able to survive in the future. This forms theprimary motivation for our programme at LeedsUniversity’s Institute of Particle Science & Engineeringto develop innovative reactor and process technologies.
Over the past few decades, a concept called processintensification has gained popularity (4,5,6). Such aconcept is often linked with green chemical science andtechnology, although in fact it came about much earlier in the 1970s when ICI (Imperial Chemical
Industries, UK) inventedthe HiGee process. Theconcept has also been usedin our reactor and processtechnology development.This article will summarisesome of the most recentdevelopments in the field,with a focus on systemsinvolving particles. Thearticle is structured in thefollowing manner: first, a
thermodynamic consideration will be made to illustratethat there is plenty of room for developing new andimproved reactor and process technologies; this will befollowed by a review of three examples of reactor andprocess developments; and finally, some concludingremarks will be made.
THERMODYNAMIC CONSIDERATIONS
For a chemical reaction or process, the endpoint isgoverned by the thermodynamic equilibrium, whereasthe rate to reach the endpoint is determined by thereaction kinetics and transport phenomena (momentum,heat and mass transfer). As a consequence, thedevelopment of new and improved reactor and processtechnologies can be realised from the two aspects ofthermodynamics and transport phenomena. Theexamples reviewed later will include both aspects.
From the thermodynamic point of view, a chemicalreaction or process involving more than one reactioncan be viewed as reaching B (endpoint) from A (startingpoint) (see Figure 1). The first law of thermodynamicsstates that one can reach B from A if mass, momentumand energy conservation laws are satisfied. However,the second law of thermodynamics says that one maynot be able to reach B even if these conservation laws are satisfied. In other words, the reaction or theprocess can only occur when the second law ofthermodynamics is satisfied. The thermodynamic lawsalso imply that if the second law says that one can reachB from A, then there is an infinite number of routesbetween A and B. As a consequence, there is plenty ofroom for developing new or improved reactor andprocess technologies. The reactor and processtechnologies used today may be the best among theroutes that have been explored, but they are by nomeans the best among all possible routes.
The reactor and process technologies used today may be the best amongthe routes that have been explored, but they are by no means the bestamong all possible routes. Thermodynamic considerations show thatthere is plenty of scope for improving existing technologies as well asdeveloping new ones.
82 Innovations in Pharmaceutical Technology
By Yulong Ding at the Institute of ParticleScience and Engineering,University of Leeds
Novel Reactor and Process Technologies: Thinking Outside the Box
As a final thermodynamic consideration here, the ‘speed’and ‘efficiency’ of a reaction or a process are oftencontradictory according to thermodynamic principles!For example, for a heat transfer process using a heatexchanger, the higher the temperature difference betweenthe hot and cold fluids, the higher the effective heattransfer coefficient to be expected. However, the largertemperature difference also implies a larger deviationfrom the equilibrium state, and hence more exergy(useful energy) is destroyed. As a result, one should notmistake ‘process intensification’ as aiming to reach theendpoint from a given starting point in the fastest andmost efficient way (7).
EXAMPLES OF NEW DEVELOPMENTS IN REACTOR AND PROCESS TECHNOLOGY
Three examples will be given in the following section toillustrate that: (i) chemical reactions can be driven to givehigher yields or conversions through ‘cheating theequilibrium’; (ii) reactors can achieve faster dynamics byusing novel heat transfer fluids; and (iii) interfacialreactors for particle production and encapsulation can bemore easily scalable.
Overcoming the Equilibrium Limitations by Using Le Chatalier’s PrincipleEquilibrium-limited chemical reactions occur in manyoptimised processes including organic syntheses in thepharmaceutical industry. In such cases, Le Chatalier’sPrinciple (illustrated in Figure 2) is relevant; thePrinciple states that selective removal of one or moreproducts from a system at equilibrium will cause moreproducts to form. The selective product removal can beachieved by using membranes, adsorption or a chemicalacceptor (1,8). For example, Ding and Alpay (9)
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Through membrane, absorption andchemical acceptor, for example
Reactorin situ D separation
A + B = C + D
A+B C
Figure 2: Overcomingthe equilibriumlimitations by usingLe Chatalier’sPrinciple
IPT 27 2008 4/12/08 11:12 Page 83
showed that the use of hydrotalcite for CO2 adsorptionin a packed bed reactor can lead to a substantialenhancement of methane conversion during steam-methane reforming; this enabled the reaction to takeplace at a much lower temperature of 400-500ºC, incomparison with the conventional process that required~1,000ºC. The packed bed reactor, however, had to beoperated cyclically due to saturation of the CO2
adsorbent. As a consequence, a radically newtechnology was developed which circulated theadsorbent particles between the reactor and adesorption column; this enabled in situ adsorption ofCO2 in the reactor and ex situ desorption of theadsorbent in the desorber, thereby achievingcontinuous operation of the system (10,11). Such aninnovative configuration was also shown to be able toenhance heat transfer by up to 200% due to the solids circulation.
The same idea could be applied to organic synthesis inthe pharmaceutical industry to enhance yields orconversions, as well as product purity. The key
challenge here is to find a suitable separation method.Adsorption-based product separation methods arefavourable in many cases over membrane-basedmethods on account of material tolerance to harshenvironments, and a wide choice and availability ofadsorbents for achieving the desired separation underreaction conditions.
Enhancing the Dynamic Control of ChemicalReactors using Novel Heat Transfer FluidsIt is well known that the crystalline form of a drug canaffect its functionality and storage stability. Currentlyavailable technologies for crystallisation control do notalways meet requirements despite a significant effortover the past few decades in terms of on-lineinstrumentation and new control strategies. A potentialmethod for improving control is to adopt novel heattransfer fluids – an area unfamiliar to the engineers andscientists working in the pharmaceutical industry.Recently, a heat transfer fluid termed nanofluid hasgained attention. Such a fluid is essentially a dilutesuspension of particles with at least one criticaldimension smaller than about 100nm, and has beenshown to have superior heat transfer properties ifproperly engineered (12). Such salient features can beused to enhance the dynamic control of chemicalreactors if heat transfer is the rate-limiting step. Forexample, for the selective reduction of an aromaticaldehyde to an alcohol in a compact reactor (asillustrated in Figure 3), we have shown that the use ofethylene glycol-based TiO2 nanofluids can enhance therate of reactor response three-fold (13).
Particle Production and Encapsulation using an Easily Scalable Interfacial ReactorManufacture of particulate solids and encapsulationare two of the most important unit operations in thepharmaceutical industry. Although numerous processroutes have been developed for such applications,scale-up has been a common issue for these processes.Here we shall briefly introduce a newly proposedinterfacial reactor to overcome the scale-up issue.Figure 4 illustrates the principle of the process, whichuses two immiscible liquids flowing in parallelthrough a channel in a controlled manner. Bycarefully selecting the two solvents and controlling thecomposition of the solutions, charge transfer andhence interfacial reaction takes place at the interface.Such interfacial reaction leads to the nucleation andgrowth of particles if appropriate precursors are used.Particles grow while being carried forward by thefluids at the interface, and are finally withdrawn fromthe interface as products at the end of the reactor. The
84 Innovations in Pharmaceutical Technology
Par
ticl
e w
ithd
raw
al
Fluid 1 recycled after treatment
Fluid 1
Fluid 2
Flow
con
trol
2Fl
ow c
ontr
ol 1
Fluid 2 recycled after treatment
Chargetransfer tointerface
Nanoparticleformation at
interface
Nanoparticlegrowth atinterface
Nanoparticleproduct from
interface
Figure 4: Schematicdiagram of a continuousinterfacial reactor forparticle production
T1
T4DTP
RCB 1
RCB 2
T2
T3
T6
T7
T5
Figure 3:Enhancing thedynamic responseof chemicalreactors usingnovel heat transfer fluids
Static mixer
Product
Gas inletLiquid inlet
Packed-bed channel
Heat transfer flu
id
IPT 27 2008 4/12/08 11:14 Page 84
two liquids are withdrawn, conditioned and recycled.For encapsulation applications, particles to beencapsulated are placed in the interface and theencapsulating agents can be either located in one ofthe fluids or produced in situ at the interface. Thecapacity of the interfacial reactor depends only on theinterfacial area, given other conditions; scale-up of thesystem can therefore be simply done by increasing theinterfacial area.
CONCLUSION
Thermodynamic laws teach us that there are numerousroutes between a starting point and an endpoint. This applies to the development of new, and theimprovement of existing, reactor and processtechnologies. The technologies used today may be thebest among routes that have been explored but they areby no means the best among all possible routes. As aconsequence, there is plenty of room for furtherdevelopment and improvement. The development ofnew and improved reactor and process technologies canbe started from two aspects of thermodynamics and transport phenomena. For equilibrium-limitedreactions, one may ‘cheat the equilibrium’ to obtainhigher yields or conversions. For reactions limited byheat transfer (heating or cooling), one can considerusing novel heat transfer fluids. Finally, one should notethat achieving the best performance of a single reactor ora single unit operation in a process does not mean it isthe best for the whole process.
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86 Innovations in Pharmaceutical Technology
Professor Yulong Ding is Professor of Chemical Engineering and Chair of Nanoparticle Engineering, at the Institute of Particle Science andEngineering, University of Leeds (UK). He joined the University in June2001 as a lecturer after previous employment with Imperial CollegeLondon, the University of Birmingham and the University of Science andTechnology Beijing (China). Yulong has been working on both experimentalaspects and mathematical modelling of particulate and multiphase reactingsystems at both small (nano and micro) and large (meso and macro)scales over the past decade. His current research activities are mainly on topics at the interface between particle science and engineering,bioengineering, energy engineering, and surface and interfacial chemistry.His research has led to over 200 technical papers, eight book chapters and ten patents. Email: [email protected]
