Australian Journal of Basic and Applied Sciences, 7(5): 366-372, 2013

ISSN 1991-8178

Simulation Of Xylitol Production: A Review

1

N. Alnur Auli, 2M. Sakinah, 1A.M. Mustafa Al Bakri, 1H. Kamarudin & 3M.N. Norazian

Center of Excellence Geopolymer and Green Technology (CEGeoGtech), School of Materials

Engineering, Universiti Malaysia Perlis (UniMAP), P.O. Box 77, D/A Pejabat Pos Besar, 01000,
Kangar, Perlis, Malaysia
2
Faculty of Chemical and Natural Resources Engineering, Universiti Malaysia Pahang (UMP),
Lebuhraya Tun Razak, 26300 Gambang, Kuantan, Pahang, Malaysia
3
School of Environmental Engineering, Universiti Malaysia Perlis (UniMAP), P.O. Box 77, D/A
Pejabat Pos Besar, 01000, Kangar, Perlis, Malaysia
Abstract: This paper reviews a recent research development on simulations biological conversion of
hemicellulosic biomass towards commercial scale production of xylitol by taking advantage of power
of biotechnology. Xylitol is a five-carbon sugar alcohol that is found in small quantities in many fruits
and vegetables. Xylitol is nearly as sweet as table sugar sucrose. Unlike sucrose, xylitol is well
tolerated by diabetics and does not cause tooth decay. As a consequence, xylitol is in demand in sugarfree confectionery. In the present paper, a continuous enzyme-catalyzed xylitol commercial scale using
the lignocellulosic biomass,was simulated by a commercial bioprocess simulator (SuperPro
Designer). In continuous mode, the objective is to maximize the amount of desired product per unit
time, whereas in batch or fed-batch modes the goal is to maximize product at the end of each batch,
leading to control challenges of a different nature. The development of computer-aided design tools for
bioprocessing began in the mid 1980s. Mathematical modelling (in the subsequent text simply
modelling) and simulation are widely used for optimally designing and operating production facilities
in most industrial sectors such as the chemical and biotechnological process industries. Study of xylitol
in continuous process using enzymes is too complex to be given tractable mathematical formulations.
In the context of optimizing simulations, a complex evaluation refers to the execution of a simulation
model (which can be extremely time-consuming). Established tool simulators for these processes
include: Aspen Plus (from Aspen Technology, Inc.), ChemCAD (from Chemstations, Inc.), Aspen
HYSYS (from Hyprotech, Ltd./AEA Engineering Software), and PRO/II (from Simulation Sciences,
Inc.). The three bioprocess simulators, Aspen Plus, HYSYS and SuperPro Designer, will be review
and compared in this research. The proposed simulator; SuperPro Designer will be selected as the best
simulator tool for production of xylitol in commercial scale.
Key words: xylitol; bioprocessing; simulation; SuperPro Designer
INTRODUCTION
The low cost and renewable nature of lignocellulosic biomass such as sugarcane bagasse, wheat straw, rice
straw, corn stover, etc. represent the ideal feedstock for their conversion into value-added products by
biotechnological routes. This lignocellulosic biomass is the most promising feedstock considering its great
availability and low cost; constituted primarily of lignin, hemicellulose(s) and cellulose (Cardona, 2007). The
carbohydrate fraction (hemicellulose and cellulose) can be depolymerised into sugars which act as a primary
carbon source for the microbial biocatalysts for the production of xylitol, ethanol, organic acids, industrial
enzymes, etc (Chandel, 2007). Xylitol is a five-carbon sugar alcohol that is found in small quantities in many
fruits and vegetables (Sirisansaneeyakul, 2009). It is one of the most expensive polyol sweeteners and has
specific health claims in the world market. It is suitable for diabetes, recommended for oral health and paranteral
nutrition. On an industrial scale, xylitol is currently produced through chemical reduction of xylose derived from
saw dust and sugarcane baggase hemicellulose hydrolysate. It is relatively expensive by about $7 kg-1
comparatively with other natural sweeteners (Rao, 2006).
In the world of software development, systems often begin as simple and well understood, and normally
contain elements such as creation of process flow diagrams, and generation of material and energy balances. To
meet the ultimate requirements, models become more complex to include calculations such as equipment sizing,
and capital and operating cost estimation. Simulation is becoming a requirement for all major process designs.
Using simulation, bioprocess engineers can identify potential problems ahead of time and take corrective action.
A common use for bioprocess simulation is for process mapping and cost analysis. Process mapping enables
investigators to analyze or predict the action of organisms in response to certain specific inputs. Cost analysis
Corresponding Author: N. Alnur Auli, Center of Excellence Geopolymer and Green Technology (CEGeoGtech), School of
Materials Engineering, Universiti Malaysia Perlis (UniMAP), P.O. Box 77, D/A Pejabat Pos
Besar, 01000, Kangar, Perlis, Malaysia
E-mail: [email protected]

366

Aust. J. Basic & Appl. Sci., 7(5): 366-372, 2013

identifies the expensive process steps and other cost items that have major impacts overall process economics.
In addition, one of the challenges for users when using such simulation tool is accumulation of the appropriate
data. Simulation can only be run until all the data is collected and put into the system (Thien, 2011). The first
step in building a simulation model is collection of information about the process.
Process simulation and modelling is the application of a range of software tools to analyse individual unit
operations (or process stages) and their relationships within the overall process. Process simulation is defined as
the utilization of computer software resources to develop mathematical models for the construction of an
accurate, representative model of a chemical process in order to understand its actual behavior during regular
plant operations (Diwekar, 2005). These tools can be used at all stages of process development, from conceptual
design, through process operation and optimization. Process simulation of xylitol using enzymes in continuous
production will study. Today the largest supplier of simulation software to the biotech and pharmaceutical
industry is Microsoft, which offers several basic software tools that can be used for simulation: Visio Constructs flow sheets with a drawing package; Excel - Process calculations are performed with spreadsheets
and reported graphically; and Project - Constructs process schedules and labor assignments. The disadvantage
of these tools is that they are not designed for bioprocess simulation.
A bioprocess is a special type of chemical process that produces biochemical products (e.g. antibiotics,
xylitol, amino acids, etc.) from microorganisms or enzymes. Bioprocesses share some common features with
general chemical processes, but differ in their kinetics of product formation, process structure (unit operations
and procedures) and operating constraints (Brunet, 2012). Most biochemical products are produced by
fermentation. In fermentation, the products are formed by catalysts that catalyse their own synthesis. Enzymes
are biological catalysts and are produced as secondary metabolites of enzyme fermentation (Saarel.U., 2003).
Study of xylitol in continuous process using enzymes is too complex to be given tractable mathematical
formulations. As research by (Barradas, 2010), where biological production of xylitol from xylose it has been
demonstrated that a low-level supply of oxygen to the culture (0.1 volume of air per volume of culture
medium per minute) yields an increase of extracellular accumulated xylitol up to 0.65 gxylitol gxylose1 by using
software Matlab Release 12 (Math Works, Inc.). Mathematical function contains multiple nonlinearities,
combinatorial relationships and uncertainties inaccessible to modeling except by resorting to more
comprehensive tools like computer simulation (Fernandez. J. A., 2008). The complexities and uncertainties in
these systems are the primary reason that simulation is often chosen as a basis for handling the decision
problems associated with them.
Process simulators offer the opportunity to shorten the time required for process development. They allow
comparison of process alternatives on a consistent basis so that a large number of process ideas can be
synthesised and analysed interactively in a short time (Tochampa, 2005). Simulation of integrated processes
also enables the study of interactions that exist between upstream and downstream processes (Rouf, 2001). To
assess the technological feasibility and obtain material and energy balances for a preliminary economic analysis,
complete process simulations were performed. Despite some expected differences between a process simulation
and real-life operation, process simulators are commonly used to provide reliable information on process
operation, owing to their vast component libraries, comprehensive thermodynamic packages and advanced
computational methods.
Aspen Plus:
Advanced System for Process Engineering (ASPEN) is a process modelling software suite designed for
batch and continuous simulation (Farid, 2007). For continuous processes, it is possible to use the conventional
Aspen Plus simulator but this requires customization for many bioprocess operations (Gosling, 2005). Aspen
Plus (developed by Aspen Technology Incorporated), is a steady-state sequential modular simulation package
used as a tool to simulate and design chemical processes. It offers the possibility to simulate various
combinations of unit operations such as reactors, distillation towers, heat exchangers and compressors using the
built-in process models (Verhoef, 2008). The steady-state is a characteristic of a condition, such as value, rate,
periodicity, or amplitude, exhibiting only negligible change over an arbitrary long period of time (infinite). It is
one of the most important process simulators in the chemical industry and oil refining process, includes
standard, ideal unit operations, such as Gibbs reaction and heat exchange models (Ye, 2009).
Essentially, the Aspen Plus simulator is made up of: i) a rich databank with pure components, binary
parameters, reactions constants, etc; ii) a vast number of thermodynamic models for the physical and transport
properties calculation; iii) a unit operation model (U.O.M). It overall model consists of 33 unit operation blocks,
one design specification and five Fortran Calculator blocks (Cimini, 2005; Somers, 2011). It also includes a
library of standard unit operation blocks (eg. pumps, heat exchanger, reactors, splitters), which represent process
taking place in an actual chemical plant (Yun, 2013). Aspen Plus includes many basic units, such as distillation
towers, drums, pumps, and heat exchangers. It does not include many specialty unit operations that are used for
particular industries, such as conveyor belts or equipment necessary for the pre-treatment of solids (Bowen,
2010). Aspen Plus includes a wide variety of thermodynamic packages, which gives the user many options as to

367

Aust. J. Basic & Appl. Sci., 7(5): 366-372, 2013

which will most accurately model any process (Haydary, 2009).

Aspen Plus can be a difficult program to learn and work with because it contains so much information. This
makes the program complicated, but also an incredibly valuable resource. When given inappropriate information
about a system Aspen Plus will sometimes give nonsensical results, but more often it will simply give an error
message. This often catches user mistakes, which is helpful, if sometimes frustrating. Considerable knowledge
of thermodynamics, chemical equipment and processes is necessary to successfully work with Aspen Plus, or
the user will end up with many errors and little information. A Microsoft Excel VBA tool has been developed to
help the engineer when performing energy and thermoeconomic analyses of processes that have been simulated
using Aspen Plus. The application is needed because Aspen Plus does not have an integrated function to
calculate the energy of the streams presented in a process, nor to evaluate thermoeconomic costs, although it
gives enough thermodynamic data and can also estimate capital costs (Querol, 2011).
After the completion of process modelling and calculations of mass and energy balances, the simulation
results can be generated and sent to another Aspen utility, Aspen Icarus Process Evaluator or Aspen IPE, which
is specialized for further economical evaluations (Kumar, 2010). Aspen IPE is designed to automate the
preparation of detailed designs, estimates, investment analysis and schedules from minimum scope definition,
whether from process simulation results or sized equipment lists (Yu, 2011; Magnusson, 2005). From study of
(Posada, 2011), the economic analysis of poly-3-hydroxybutyrate (PHB) production from glyceol was estimated
by using Aspen Icarus. In economic terms the best technological scheme for PHB production from crude
glycerol includes three important features as follows: (i) purification of crude glycerol up to 98 wt%, (ii) a two
continuous fermentation stages, with operating times of 21 and 22.5, h respectively and finally (iii) the PHB
recovering performed with the Downstream Process I, which is similar to the BIOPOL flow sheet.
Other disadvantages of Aspen Plus are the kinetic and models must define for simulation and in some cases
it is hard to converge. The model library of Aspen Plus is limited in type and number of models of process unit
operations (Larrson, 2011). The properties for components not included in the Aspen Plus database were
obtained from a custom property database developed by National Renewable Energy Laboratory (NREL). Heat,
work, and material stream flows, as well as process conditions from Aspen Plus simulations are imported into
Excel for use in the economic analysis.
Some research had used Aspen Plus for conversion of glycerol to added-value components. Because of both
the petrochemical character of Aspen Plus and its modular-sequential approach, there are not available kinetic
models describing the biotechnological processes such as fermentations or enzymatic reactions. Therefore, it is
required to work with the available interface between Aspen Plus and Excel. The specific compounds involved
in the different processes of raw glycerol conversion to added-value products such as: free fatty acids, alkyl
esters, proteins, salts, cell mass strains, enzymes, and other complex molecules produced by reactive-extractive
process are not available on the Aspen Plus Database (Duque, 2011).
Same study also by (Limniyakul, 2007), where due to unavailable structure of reactants and products in the
library of Aspen Plus, the major components of Jatropha which were triglyceride, diglyceride and
monoglyceride of oleic and linoleic acid were draw by GaussViewW. After drawing, the structures were
optimized by GAUSSIAN 03W in order to obtain the stable structure. All of these structures were used in Aspen
Plus for finding the parameter such as boiling point, molecular weight, heat capacity, coefficients for antoine
equation. The simultaneous production of bioethanol and xylitol from rye straw is investigated by (Franceschin,
2011) that was then implemented using the software Aspen Plus. The optimization of the process energy duties
is carried out by means of the pinch technology analysis. Mass balances from the simulation are used in order to
size the equipment and calculate the capital investment. As a result, 736 kg/h of xylitol, 82 kg/h of cells, 52 kg/h
of ethanol are obtained; in the product also arabitol, CO2, unreacted xylose and arabinose are present, according
to the yields reported.
Aspen HYSYS:
Aspen HYSYS (HYprotech SYStem) by Aspen Technology is one of the major process simulators that are
widely used in chemical and thermodynamic process industries today. It also specializes on steady state analysis
same as Aspen Plus (Dash, 2008). Aspen HYSYS is designed specifically for a continuous process of multiple
process units. It is not designed to handle batch, semi-batch, or semi-continuous process units (Hanyak, 2012).
Aspen HYSYS had to advantage to export the process design to Aspen Icarus Process Evaluator (Aspen IPE) for
cost estimation. The cost estimation was based on equipment costs given by Aspen IPE, raw material costs
provided by user and utility costs from Aspen IPE database. Otherwise, the thermodynamic packages
incorporated in Aspen HYSYS had limited thermodynamic data on the biomass components.
A difficulty in modelling the bioprocesses using HYSYS process simulation software was to obtain the
thermodynamic package that incorporated biological materials in the design. The fermentation, anaerobic
digestion and transesterification processes had least thermodynamics properties available for modelling. Most of
the biomass components were manually entered using the user-defined method and the structures of each
compound were constructed using standard software (SYMYX Draw 3.2). Property estimation methods for

368

Aust. J. Basic & Appl. Sci., 7(5): 366-372, 2013

HYSYS were used to predict the interaction parameters. Conversion reactors were used for single reactions.
Tanks were used for multiple reactions, as conversion reactors in HYSYS were incapable of handling multiple
reactions.
Study by (West, 2008), continuous biodiesel processes by using waste vegetable oil feedstock were
designed and simulated in HYSYS. HYSYS was selected as a process simulator for both its simulation
capabilities and its ability to incorporate calculations using the spreadsheet tool .Components not available in
the HYSYS library was specified using the Hypo Manager tool. However, specification of a component
requires input of a number of properties, such as normal boiling point, density, molecular weight, as well as the
critical properties of the substance were obtained from the ASPEN Plus component library. The initial cost
estimations of the processes were also exported to ICARUS Process Evaluator (IPE). As study by (Sengupta,
2010), the economic analysis was also performed in ICARUS for process for fermentation of biomass to
ethanol. The design has three sections, a pre-treatment section, a fermentation section and a purification section.
The total project capital cost was $20 million. The operating cost was $81 million per year which included raw
material costs of $54 million per year. A minimum product selling price computed from the operating cost was
set at $1.52/gallon for ethanol.
For process economics, Aspen In-Plant Cost Estimator was used. It has been used for over 30 years in
commercial plants and engineering designs, and provides more accurate estimation. Aspen In-Plant Cost
Estimator provides specifications for detailed design, estimation and economic data, allowing quick
modifications of the process equipment and sensitivity analysis. The alkali-catalyzed process using fresh
vegetable oil had the lowest total capital investment, but the supercritical process was the most economically
feasible overall, providing a lower manufacturing cost and higher net present value and a discounted cash flow
rate of return (Lee, 2011).
SuperPro Designer:
SuperPro Designer is a professional process simulator developed by Intelligen Incorporated, which
facilitates modeling, evaluation and optimization of integrated processes in a wide range of industries such as in
pharmaceutical industries, agrochemicals, food processes, water purification and end-of-pipe treatment
processes. It is also designed specifically for processes including biological components (Athimulam, 2006). It
combines the drawing, calculation and scheduling features of the three Microsoft packages; Excel, Project and
Visio into a single, moderately priced package (Gosling, 2003). SuperPro Designer can handle batch and
continuous processes equally well; whereas the other three tools are practically limited to batch or continuous
processes. (Petrides, 2002). Besides process modeling, Superpro Designer has many advanced convenient
features such as material and energy balances calculations, extensive databases for chemical component and
mixture as well as equipment and resource, equipment sizing and costing, thorough process economics, waste
stream characterization, etc (Ernst, 1996). This program is also capable of providing equipment cost used for the
plant (Qureshi, 2013). All these features are quite useful when analysing the process models (Yu, 2011).
SuperPro Designer includes unit operations specific to biological operations, such as fermentors and
strainers that Aspen lacks. As study by (Malakahmad, 2013; Vucurovi, 2012), the biodegradation process of a
small-scale anaerobic bioreactor was simulated using SuperPro Designer and process simulation flow sheet,
materials registration and process reactions were conducted during model setup However, SuperPro Designer
has significantly less rigorous thermodynamic packages and far less information about components in databases.
This often forces the user to research outside of the program in order to gather enough information for a
successful simulation. SuperPro Designer enables an easy and user-friendly approach than Aspen Plus (Biwer,
2004). However, much more care is required of the user to successfully run a simulation in SuperPro Designer
because it will give physically impossible results. SuperPro Designer also includes a costing feature that certain
versions of Aspen Plus lack. It is very helpful to get an approximate cost of equipment and plant operating cost
as the simulation is completed (Bowen, 2010).
SuperPro Designer also offers a database feature to log equipment and utility capacities. This package has
the added advantage that it was specifically developed for simulation of bioprocess unit operations and
processes. It is user friendly and set up to capture the unique unit operational data requirements of biological
processes (Gosling, et. al., 2003). SuperPro Designer is relatively simple and fast to set up a flowsheet for an
entire process where it does not require integration of differential equations (Kawachale, 2011). This shortens
the computation time and enables the user to evaluate a larger number of scenarios in a shorter period
(Trifkovic, 2000). It also had default values for many of the input data required for simulation that could be used
when experimental data were not readily available or as a reference to check against. However, one of the key
disadvantages was that it could not capture the desired dynamic behaviour capabilities related to time-dependent
operations (Farid, 2007). The main advantages of this simulator consist in a large data base of specific chemical
compounds and unit operations, and the evaluation of economical and ecological process performance indexes
(Taras, 2011). The unit operation models in SuperPro Designer are not very complex. If more accurate results
are desired, the solutions obtained with SuperPro Designer at the large scale of the entire process can be refined

369

Aust. J. Basic & Appl. Sci., 7(5): 366-372, 2013

at the small scale of unit operations. Most of all chemical and biochemical engineering simulators are not
equipped with optimization tools. In very few simulators (e.g. Aspen Plus) there are some optimization tools,
but the formulation of optimization problems and techniques are severely imposed. SuperPro Designer doesnt
contain any optimization tools for optimization purposes; this was linked with Matlab using automation Clientserver of Matlab Component Object Module (COM) technology (Woinoraso, 2009).
A study by (Rouf, 2001), production of tissue plasminogen activator (t-PA) from Chinese hamster ovary
(CHO) cells are using Aspen BPSTM and SuperPro Designer. However, the economic evaluator of Aspen
BPSTM, which has been derived from the chemical process simulator AspenPlusTM, is geared more towards
chemical processes. Its calculation mode is rigorous and requires a lot of data from a real project to make
appropriate use of the available options. SuperPro Designer on the other hand, has an economic evaluator that
is specifically developed for bioprocesses. It is simple and easy to use. (Vlysidis, 2011) have design and
simulation in HYSYS of biodiesel processes involving two different feedstocks (virgin vegetable oil and waste
cooking oil) catalysed by two different catalysts (alkali and acid catalyst). It has technically and economically
assessed and compared these schemes. They have performed sensitivity analysis and they have indicated that the
capacity and the prices of feedstock and products have a great impact on the plants profitability. A similar study
has studied and compared the economic viability of three biodiesel scenarios that use different catalysts by using
the process simulation software SuperPro.
Research by (Kawachale, 2011), the membrane based processes for the recovery of isoflavones from red
clover flowers shows purchasing cost of $3/kg and $0.75/kg was assumed for dry flowers and ethanol
respectively. Also, in order to keep the equipment costs lower, the ultrafiltration modules in the membrane
based processes were modelled to be constructed out of plastic, which was appropriate for moderate pressure
operations (550 kPa). The processes were evaluated for a 15 year project life time, assuming the plant to be
operational for 330 days/year. Alternatively, in a fed-batch process a constant substrate concentration can be
maintained during the fermentation. C. boidinii NRRL Y-17231 fermentations achieved 75% theoretical xylitol
yield in a fed-batch process compared to 53% theoretical yield in batch process. The maximum productivity
(0.46 g/l.h) in the fed-batch process was twice the maximum productivity observed in the batch process
(Rangaswamy, 2003).

(b)
Conclusions:
Process simulation is an important tool in bioprocess industry. The benefits of simulation for bioprocess
improvement, assessment and expand have been realized previously. Basically, process development is
shortened by application of process models and simulators. In simulation, the tasks provided such as; represent
the entire process on the computer, perform material and energy balances, estimate the size of equipment,
estimate the cycle time of the process and perform cost analysis. SuperPro Designeris windows-based software
which can be used to design and assess manufacturing of the product and decide on treatment methods,
pollution prevention and waste minimization approaches, at the same time. Application of SuperPro Designer
has been reported for process simulation in production of xylitol, pyruvic acid, monitoring of biopharmaceutical
facility, fuel ethanol production and biodiesel production costs analysis. As a conclusion, Super Pro Designer
can provide sophisticated modeling for bioprocess for a batch and continuous processes.
ACKNOWLEDGMENTS
King Abdul Aziz City Science and Technology (KACST) funded this study. Also, we extend our appreciation
to the Green Concrete@UniMAP and to all of the people who contributed to the successful completion of this
study.
REFERENCES
Athimulam, A., S. Kumaresan, 2006. Modelling and Optimization of Eurycoma Longifolia Water Extract
Production. Food and Bioproducts Processing, pp: 139-149.
Barradas, J.S., C.G. Orijel, 2010. A stoichiometric Analysis of biological Xylitol Production. Biochemical
Engineering Journal, pp: 1-9.
Biwer, A., E. Heinzel, 2004. Enzyme and Microbial Technology, pp: 642-650.
Bowen, E., S.C. Kennedy, 2010. Ethanol from Sugar Beets: A Process and Economic Analysis. United
States: Worcester Polytechnic Institute.
Brunet, R., G.G. Gosalbez, 2012. Hybrid Simulation-optimization Based Approach for The Optimal Design
of Single-product Biotechnological Processes. Computers and Chemical Engineering, pp: 125-135.
Cardona, C., A. Autunes, 2007. Fuel Ethanol Production: Process Design Trends. Bioresource Technology,
pp: 2415-2457.

370

Aust. J. Basic & Appl. Sci., 7(5): 366-372, 2013

Chandel, A.K., S. Antunes, 2007. Dilute Acid Hydrolysis of Agro-Residues for the Depolymerization of
Hemicellulose: State-of-the-Art. Biotechnology, pp: 201-208.
Cimini, S., M. Prisciandaro, 2005. Simulation of a Waste Incineration Process with Flue-gas Cleaning and
Heat Recovery Sections Using Aspen Plus. Waste Management, pp: 171-175.
Dash, S.M., 2008. Study of Cryogenic Cycles with Aspen- HYSYS Simulations. India: University Rourkela.
Diwekar, U., 2005. Green Process Design, Industrial Ecology, and Sustainability: A Systems Analysis
Perspective. Resources, Conservation and Recycling, pp: 215-235.
Duque, J.A., 2011. Design and Analysis of Technological Schemes for Glycerol Conversion to Added Value
Products. Columbia: Universidad Nacional de Colombia.
Eliassona, A., J.H.S. Hofmeyrc, 2001. The Xylose Reductase/Xylitol Dehydrogenase/Xylulokinase Ratio
Affects Product Formation in Recombinant Xylose-utilising Saccharomyces Cerevisiae. Enzyme and Microbial
Technology, pp: 288-297.
Ernst, S., O.A. Garro, 1996. Process Simulation for Recombinant Protein Production: Cost Estimation and
Sensitivity Analysis for Heparinase I Expressed in Escherichia coli. Biotechnology and Bioengineering, pp:
575-582.
Farid, S.S., A. Washbrook, 2007. Modelling Biopharmaceutical Manufacture: Design and Implementation
of SimBiopharma. Computers and Chemical Engineering, pp: 1141-1158.
Fernandez, J.A., J. Banga, 2008. Scatter Search for Chemical and Bio-Process Optimization. Spain:
Instituto de Investigaciones Marinas.
Franceschin, G., M. Sudiro, 2011. Conversion of Rye Straw Into Fuel and Xylitol: A Technical and
Economical Assessment Based on Experimental Data. Chemical Engineering Research and Design, pp: 631640.
Gosling, I., 2005. Process Simulation and Modeling for Industrial Bioprocessing:Tools and Techniques.
Industrial Biotechnology, pp: 1-7.
Guo, C., M. Jiang, 2005. Screening and Characterization of Yeasts for Xylitol. Journal of Applied
Microbiology, pp: 1364-5072.
Hanyak, M.E., 2012. Chemical Process Simulation and The Aspen HYSYS Software. Lewisburg: Bucknell
University.
Haydary, J., 2009. Steady-State and Dynamic Simulation of Crude Oil Distallation Using Aspen Plus and
Aspen Dynamics. Petroleum & Coal, pp: 100-109.
Kawachale, N., A. Kumar, 2011. Simulation, Scale-up and Economics of Adsorption and Membrane Based
Processes for Isoflavones Recovery. Chemical Engineering Research and Design, pp: 428-435.
Klemola, K., I. Turenan, 2001. State of Mathematical Modelling and Simulation in the Finnish Process
Industry, Universities and Research Centres. Technology Review, pp: 124-130.
Kumar, S., 2010. Modelling and Simulation of Ethyl Acetate Reactive Distillation Column Using ASPEN
PLUS. Chemical Engineering, pp: 10-17.
Larrson, M., 2011. Evaluation of Research Method. German: Energisystem.
Lee, S., D. POSARAC, 2011. Process Simulation and Economic Analysis of Biodiesel Production
Processes using Fresh and Waste Vegetable Oil and Supercritical Methanol. Chemical Engineering Research
and Design, pp: 2626-2642.
Limniyakul, W., 2007. Application of Reactive Distillation for Biodiesel Production Enhancement. India,
Kasetsart University.
Magnusson, H., 2005. Process Simulation in Aspen Plus of an Integrated Ethanol and CHP Plant.
Maldives: Energy Engineering.
Malakahmad, A., N.E.A. Basri, S.M. Zain, 2013. Design and Process Simulation of a Small Scale WasteTo-Energy Bioreactor . Journal of Applied Sciences, pp: 2586-2591.
Papavasileiou, V., A. Koulouris, 2007. Optimize Manufacturing Pharmaceutical Products With Process
Simulation and Production Schedulling Tools. Chemical Engineering Research and Design, pp: 1086-1097.
Petrides, P., A. Koulouris, 2002. The Role of Process Simulation in Pharmaceutical Process Development
and Product Commercialization. Pharmaceutical Engineering, pp: 1-8.
Posada, A., M. Naranjo, 2011. Design and analysis of poly-3-hydroxybutyrate production processes from
crude glycerol. Process Biochemistry, pp: 310-317.
Querol, E., B.G. Reugueral, 2011. Novel Application for Energy and Thermoeconomic Analysis of
Processes Simulated with Aspen Plus. Energy, pp: 964-974.
Qureshi, N., B.C. Saha, 2013. An Economic Evaluation of Biological Conversion of Wheat Straw to
Butanol: A biofuel. Energy Conversion and Management, pp: 456-462.
Rao, R.S., P. Joythi, 2006. Xylitol Production from Corn Fiber and Sugarcane Bagasse Hydrolysates by
Candida Tropicalis. Bioresource Technology, pp: 1974-1978.
Rouf, S.A., P.L. Douglas, M.M. Young, 2001. Computer Simulation for Large Scale Bioprocess Design.
Biochemical Engineering Journal, pp: 229-234.

371

Aust. J. Basic & Appl. Sci., 7(5): 366-372, 2013

Saarel, U., K. Leiviska, 2003. Modelling of A Fed- Batch Fermentation Process. Finland: Control
Engineering Laboratory.
Sengupta, D., 2010. Integrating Bioprocess Into Industrial Complexes For Sustainable Development.
Jadavpur: Graduate Faculty of the Louisiana State University and Agricultural and Mechanical College.
Sirisansaneeyakul, S., R. Chainoy, 2009. Xylitol Production by Liquid Emulsion Membrane Encapsulated
Yeast Cells. Journal Chem Technol Biotechnol, pp: 1218-1221.
Somers, B., A. Mortazi, 2011. Modeling Water/ Lithium Bromide Absorption Chillers in ASPEN Plus.
Applied Energy, pp: 4127-4232.
Taras, S., A. Woinaroscomy, 2011. Multi- Objective Optimization of Pyruvic Acid Bioprocess with A
Mathlab-SuperPro Designer Interface. Scienece Bulletin, pp: 1454-2331.
Thien, Y.N., 2011. BioMASS v2.0: A New Tool For Bioprocess Simulation. Biosystems Engineering, pp:
1-19.
Tochampa, W., A. Sirisansaneeyakul, 2005. A model of Xylitol Production by The Yeast Candida Mogii.
Bioprocess Biosyst Eng, pp: 175-183.
Trifkovic, M., S. Cardoso, 2000. Model Assisted Design and Simulation of a Pharmaceutical Batch Process;
Manufacturing of Clopidogrel Bisulfate. Chemical Engineering, pp: 100-106.
Verhoef, A., J. Degreve, 2008. Simulation of a Hybrid PervaporationDistillation Process. Computers and
Chemical Engineering, pp: 1135-1146.
Vlysidis, A., N. Binns, 2011. Techno-economic Analysis of Biodiesel Biorefineries: Assessment of
Integrated Designs for The Co-production of Fuels and Chemicals. Energy, pp: 4671-4683.
Vucurovi, D.G., S.N. Dodic, 2012. Process Model and Economic Analysis of Ethanol Production from
Sugar Beet Raw Juice as Part of the Cleaner Production Concept. Bioresource Technology, pp: 367-372.
West, A.H., D. Posarac, 2008. Assessment of Four Biodiesel Production Processes using HYSYS.Plant.
Bioresource Technology, pp: 6587-6601.
Woinoraso, A., S. Taras, 2009. Simulation and Optimization of Citric Acid Production with SuperPro
Designer using a Client-Server Interface. Chimie, pp: 978-986.
Ye, G., D. Xie, 2009. Modeling of Fluidized Bed Membrane Reactors for Hydrogen Production from Steam
Methane Reforming with Aspen Plus. International Journal of Hydrogen Energy, pp: 4755-4765.
Yu, F., 2011. Process Modeling of Very-high-gravity Fermentation System Under Redox Potentialcontrolled Conditions. Canada: University of Saskatchewan.
Yun, H., M. Wang, 2013. Process Simulation and Energy Optimization of The Enzyme-catalyzed Biodiesel
Production. Energy, pp: 84-96.

372