Separation & Purification Reviews

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Purification of Lactic Acid Produced by

Fermentation: Focus on Non-traditional
Distillation Processes

Andrea Komesu, Maria Regina Wolf Maciel, Johnatt Allan Rocha de Oliveira,
Luiza Helena da Silva Martins & Rubens Maciel Filho

To cite this article: Andrea Komesu, Maria Regina Wolf Maciel, Johnatt Allan Rocha de Oliveira,
Luiza Helena da Silva Martins & Rubens Maciel Filho (2017) Purification of Lactic Acid Produced by
Fermentation: Focus on Non-traditional Distillation Processes, Separation & Purification Reviews,
46:3, 241-254, DOI: 10.1080/15422119.2016.1260034

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Separation & Purification Reviews, 46: 241–254, 2017
Copyright © Taylor & Francis Group, LLC
ISSN: 1542-2119 print / 1542-2127 online
DOI: 10.1080/15422119.2016.1260034

Purification of Lactic Acid Produced by Fermentation:

Focus on Non-traditional Distillation Processes
Andrea Komesu,1 Maria Regina Wolf Maciel,1 Johnatt Allan Rocha de Oliveira,2 Luiza Helena da Silva
Martins,1 and Rubens Maciel Filho1
1
School of Chemical Engineering, University of Campinas (UNICAMP), Campinas, São Paulo,
Brazil
2
Nutrition College, Federal University of Pará (UFPA), Belém, Pará, Brazil

Lactic acid is commonly used in a wide range of fields such as cosmetics, pharmaceutical
products, chemistry and food. During the last years, its use for new applications such as
production of biodegradable and biocompatible polymers, green solvents and oxygenated
chemicals have received considerable attention. However, the relatively high production cost
of lactic acid hinders many large-scale applications. In order to cheapen lactic acid production
processes, it is necessary to develop more efficient methods of separation and purification.
This work reviews some promising non-traditional distillation processes that are currently
employed for lactic acid recovery, focusing on reactive distillation and molecular distillation.
Advances in such distillation-based processes, their drawbacks and concluding remarks are
also presented.

Keywords: Lactic acid, purification, fermentation, separation processes, traditional distilla-

tion, reactive distillation, molecular distillation

INTRODUCTION L-(+)-lactic acid, the biological form, and D-(−)-lactic acid.

The industrial biotechnology has a significant social and
economic importance due to the possibility of using renew-
able resources and the large number of metabolites of
industrial interest produced from these processes.
Environmental pollution is a consequence of technological
development, so the implementation of cleaner technologies
that use less energy is better for the environment, which is
becoming a necessity in all industries. The biotechnological
process for lactic acid production by fermentation is an
important technological biomass-based platform, which has
attracted much attention from the researchers.
Lactic acid, CH3-CHOH-COOH or 2-hydroxypropionic
acid (CAS 50-21-5) was discovered in 1780 by the Swedish
chemist Scheele from sour milk (1). It has two enantiomers:
Received 23 March 2016, Accepted 1 November 2016.
Address correspondence to Andrea Komesu, School of Chemical
Engineering, University of Campinas (UNICAMP), 500 Albert Einstein
Ave., Cidade Universitária Zeferino Vaz, 13083-852 Campinas, São
Paulo, Brazil. E-mail: andrea_komesu@hotmail.com
It is used as feedstock in a wide variety of applications like
pharmaceutical products, pH regulation, food, pesticide and
polylactic acid (PLA) biopolymer. PLA has the potential to
provide a new biodegradable product platform to compete
with hydrocarbon-based thermoplastic (2), which is used in
food packaging including rigid containers, shrink wrap and
short shelf-life trays, as well as mulch films and rubbish
bags (3). The exploitation of full PLA potential, however,
depends largely on how cost-effectively it can be produced
with high levels of purity. The major technology barrier in
cost-effective production of high-purity lactic acid is its
downstream processing (DSP) (4). Thus, development of
an efficient method for lactic acid DSP from fermentation
broth is crucial, because the cost of these steps is typically
30–40% of the total production costs (5).
Bearing in mind the importance of DSP for lactic acid
production, reactive distillation and molecular distillation,
which are non-traditional distillation processes, are promis-
ing technologies for the recovery of high-purity lactic acid
with a high yield from the fermentation broth. Reactive
distillation is an attractive alternative to conventional
242 A. KOMESU ET AL.
processes because of the following reasons: simplification or
elimination of the separation system leading to capital
savings, improved conversion of reactants, reduced recy-
cling costs, improved selectivity of desired products,
reduced catalyst requirement, reduced by-product formation
and allow heat integration (6). Molecular distillation, as an
environmental friendly and gentle technique (7), has been
recognized as a promising technology mainly because of its
low evaporation temperature and short residence time,
which considerably reduces the effects of thermal decom-
position. In general, these peculiarities show the high
potential of this process in the separation, purification and/
or the concentration of natural products, usually constituted
by complex and thermally sensitive molecules (8).
In this work, information about different non-traditional
distillation-based processes that can be employed for lactic
acid recovery and were attempted to overcome the problems
of traditional processes are reviewed.
FERMENTATION
Lactic acid production from microbial fermentation represents
more than 50 % of world production (9). It has attracted
interest due to numerous advantages compared to the chemical
synthesis: it produces pure L(+) (or S) isomers and uses renew-
able resources as fermentation substrate. The fermentation
process is characterized by biological degradation of substrate
(glucose) by a population of microorganisms (biomass) into
metabolites such as ethanol, citric acid and lactic acid (10).
The raw materials used as substrates in microbial fer-
mentation for lactic acid production can be starch such as
wheat, maize, cassava, potato, rice, rye, barley (11–13),
lignocellulose (14), whey (15), sugar beet (16) or sugarcane
molasses (17). A fermentation product with high purity is
obtained when a pure substrate is used, such as sucrose from
sugarcane and sugar beet, resulting in the reduction of
purification cost. However, the high value of sugarcane
makes such process economically unviable. On the other
hand, the use of waste products from food industries and
sugarcane mills is advantageous from environmental and
economic standpoints.
FIGURE 1 General process of lactic acid downstream processing.
Carbohydrates are fermented to lactic acid by bacteria
and fungi. The choice of these microorganisms depends
primarily on the carbohydrate to be fermented, since the
metabolism of microorganisms depends on the carbon
source used. Besides the substrate source and microorgan-
ism used, some parameters may affect the fermentation
efficiency such as the pH and temperature of the medium,
nitrogen and vitamins sources, fermentation operation
mode, and by-products formation. The fermentation condi-
tions also determine the quality of the broth and its suit-
ability for DSP options (2). Currently, a typical fermentation
broth is composed by a diluted solution of lactic acid (1.6–
16 wt.%), lactate salts, residual sugars, biomass, nutrients
and other organic acids. Several reviews have been pub-
lished about the development of biotechnology processes
for lactic acid production by fermentation (14, 18–20).
The demand for lactic acid has been estimated to grow
yearly by 5–8%. The annual world market for lactic acid
production is forecasted to reach about 400,000 metric tons
by the year 2017 (18).
DOWNSTREAM PROCESSING/PURIFICATION OF
LACTIC ACID
After the fermentation process, the fermentation broth with
diluted solution of lactic acid and/or lactate salts needs
acidification and purification steps for further refining.
Commercial lactic acid can be classified in four groups
according to their composition: food grades (25–90% lactic
acid content); pharmaceutical and cosmetic grades (90%
lactic acid content); industrial grades (88% and 90% lactic
acid content); and specialty grades (80%, 90% and 98%
lactic acid content) (21). To achieve these purity levels, a
number of steps in lactic acid DSP are applied, as illustrated
in the general process in Figure 1. There are many alter-
natives and combinations of steps described in the literature,
but in general for the recovery and purification of lactic acid
the following steps are required:
● Removal of biomass from the broth by filtration or
centrifugation.
 LACTIC ACID PURIFICATION 243

● Acidification of the broth to convert lactate salts to
lactic acid. Neutralization of broth with bases (Ca
(OH)2, NH4OH, NaOH and others) during the fermen-
tation is used to control the pH, so lactate salts are
produced from lactic acid [Eq. (1)]. To convert lactate
salts into lactic acid, precipitation of salts by a strong
acid is the common DSP [Eq. (2)].
Neutralization : 2CH3 CHOHCOOH þ CaðOH Þ2
! CaðCH3 CHOHCOOÞ2 þ 2H2 O
(1)
Lactic acid þ calcium hydroxide
! calcium lactate salt þ water
Acidification : CaðCH3 CHOHCOOÞ2 þ
H2 SO4 ! 2CH3 CHOHCOOHþ
(2)
CaSO4 Lactate salt þ sulfuric acid
! lactic acid þ calcium sulfate
● Separate lactic acid from the obtained inorganic salt
formed. The separation can be carried out by precipitation,
liquid–liquid extraction and ion exchange. Direct removal
of lactic acid from the broth without neutralization can be
achieved by a separation method integrated with fermenta-
tion, such as membrane separation, adsorption and ion
exchange.
● Concentration of lactic acid. Solvent extraction,
separation with membranes, evaporation, crystalliza-
tion and distillation process, including promising tech-
nologies such as reactive distillation and molecular
distillation, can increase the concentration of lactic
acid.
● Removal of impurities. Impurities such as residual
sugars, sugar degradation products, acetic acid and
formic acid can be removed by chromatography and
ion exchange.
Separation processes are essential to the chemical and
related industries. Approximately 40–70% of operating and
capital costs are due to the separation steps (22). In lactic
acid production processes, effective purification methods are
required for economic viability. Although the difference
between the boiling point of lactic acid and water is rela-
tively large, it is almost impossible to obtain pure crystalline
lactic acid. This is because lactic acid has high affinity with
water and dimer forms when the lactic acid concentration is
sufficiently high (23). Several works and patents about
lactic acid separation technologies have been published.
Table 1 illustrates a brief summary of the advantages and
disadvantages of different DSPs for lactic acid. In precipita-
tion process, an excess of calcium carbonate or calcium
hydroxide is added to the fermenter to neutralize the acid
produced, maintaining the pH around 5–6, and to produce
calcium lactate (24). Neutralization is performed because
fermentation operates more efficiently at pH near neutrality:
the fungus does not have a good tolerance to acidic condi-
tions and lactic acid production is reduced in the case of

TABLE 1
Advantages and disadvantages of separation processes for lactic acid recovery

Separation
process Advantages Disadvantages

Precipitation Easy applicable in industrial plants Simple operation High sulfuric acid consumption
Generation of gypsum, which requires landfill disposal
Low product purity
Liquid–liquid No generation of gypsum Extractant needs to be regenerated by distillation or back-extraction (stripping)
extraction Reduction in the risk of thermal decomposition Product purity is not high
Conventional extraction agents show very unfavorable distribution coefficients
Membrane Great flexibility in scale of production High cost of membranes
processes High selectivity Membrane fouling
High levels of purification Polarization problems
Possibility of integration with conventional fermenters, Difficult to scale up
reducing the equipment investment cost
Molecular Reduction in the risk of thermal decomposition Difficult to scale up
distillation High levels of purification Require high vacuum conditions
No use of solvents
No further purification is needed
Reactive Integration of reaction and separation in the same apparatus Process is complex
distillation High levels of purification Applied specifically to reversible chemical reactions in the liquid phase
Lower energy consumption Applications are limited to systems in which the reaction rates are fairly high
and there is no mismatch of temperatures favorable for reaction and separation
Corrosion and separation problems by the use of homogeneous catalyst
244 A. KOMESU ET AL.
bacteria. Process improvements have been developed by
researchers (12, 25–28). Lactic acid of technical grade
(22–44%) is obtained using precipitation. However, for
higher value-added applications, lactic acid with high purity
and thermal stability are required. For high-purity product,
the technical-grade lactic acid is esterified with methanol or
ethanol and the methyl or ethyl lactate is easily recovered by
distillation, re-hydrolyzed with minimum water, evaporated
and the alcohol recycled (20). Separation of lactic acid by
precipitation has serious disadvantages: high cost of
reagents, filtration process and other separation processes,
especially when lactic acid of high purity is required. From
an environmental standpoint, a large amount of wastewater
is generated. Furthermore, while producing one ton of lactic
acid, approximately one ton of low-value calcium sulfate is
generated (4), which poses serious problems in terms of
waste treatment.
Another method of lactic acid purification is solvent
extraction or liquid–liquid extraction. In the extraction
process, one or more components (solutes) in a feed
mixture are transferred to another immiscible liquid (sol-
vent). Thus, the solvent partially dissolves certain species
of the liquid feed, effecting at least a partial separation of
the feed components (29). Many studies have been devel-
oped over the years in order to improve solvent extraction
processes (30–32). The advantage of this method is that it
does not generate solid waste (gypsum) as the precipita-
tion method does. However, it requires a high exchange
area for efficient separation, requiring expensive equip-
ment and solvent recovery in stripping steps. Also, the
high toxicity of the extractant toward microorganisms
limits its application to in situ extractive fermentation
(33). Liquid–liquid extraction is not generally applied in
industrial processes, since the conventional extraction
agents have unfavorable distribution coefficients for
organic acids (34) and extractant of low toxicity and
high extractability is indispensable for an efficient process
(33).
Membrane separation processes are also used for the
purification of lactic acid. These processes are based on
the transfer of solutes through a semi-permeable physical
barrier that separates two phases, restricting the transport of
components from one phase to another. Membrane pro-
cesses may include microfiltration, ultrafiltration, nanofiltra-
tion or reverse osmosis or combinations thereof (19). Many
studies of lactic acid recovery using membranes have been
reported over the years (15, 35–38). They showed that
membrane separation processes offer a great flexibility in
the scale of production depending on market demand.
Because of high selectivity, membranes can ensure high
levels of purification and separation. In addition, mem-
branes can be integrated with conventional fermenters,
allowing the simultaneous production and purification, elim-
inating the need of additional separation units, and reducing
the equipment investment cost (4). Despite its advantages,
the high cost of membranes, the polarization and fouling
problems limit the use of the electrodialysis processes in
large scale. Therefore, more research should be done to
optimize this process (39).
Another method of separation and purification of lactic
acid is based on esterification (40, 41). In this case, the
lactic acid in the fermentation broth is simply esterified
with an excess of alcohol and catalyst to the corresponding
esters (ethyl or methyl lactates), separated through distilla-
tion from other organic impurities, and then re-hydrolyzed
to obtain pure lactic acid (42). In this method, a reactor
followed by a distillation train is necessary, increasing the
equipment cost. This disadvantage can be overcome using
reactive distillation.
In recent years, many studies have been performed to
solve the problems of traditional separation processes
through non-traditional distillation separations. The next
sections review the advances in such processes.
DISTILLATION PROCESS
Distillation is the oldest and the most universal process of
chemical technology and other branches of industry incor-
porating separation of mixtures (43), present in 90–95% of
all separations (22). Distillation is frequently the first
choice because of knowledge and proven performance.
Distillation depends on the differences in component boil-
ing points. When heat is provided to a liquid mixture there
is a partial vaporization, forming two phases (liquid and
vapor) of different compositions, due to the volatility dif-
ference of the various components of the initial liquid
mixture.
There are many industrial applications of distillation
process and many studies have been conducted to optimize
the process in order to achieve greater efficiency and
decreased energy costs, mainly in the hybrid distillation
processes. Hybrid distillation combines different processes
such as absorption, extraction and others with the conven-
tional distillation.
Conventional distillation at normal temperature and
pressure is inefficient to recover lactic acid from a crude
acidified fermentation broth (44). Therefore, crude lactic
acid can be converted to esters first before being hydrolyzed
into lactic acid by a reactive distillation unit. It is an alter-
native technique for lactic acid purification with high purity
and efficiency (45). The technology of reactive distillation
offers a large number of advantages over the conventional
sequential approach of reaction and separation (46).
Another technology that may be used for recovery and
purification of lactic acid from fermentation broth is mole-
cular distillation. Molecular distillation has been success-
fully applied in medicine, food, chemical and cosmetic
industries (47). Reactive distillation and molecular distilla-
tion are discussed below.

Reactive Distillation
Reactive distillation (RD) was first patented in 1921 by
Backhaus (22) and has been the object of attention until
the present day. It is a unit operation in which chemical
reaction and distillation separation are carried out simulta-
neously within a fractional distillation apparatus (48). The
term catalytic distillation is also used for such systems
where a catalyst (homogeneous or heterogeneous) is used
to accelerate the esterification (49). RD can be categorized
into two main types of mode operation: continuous and
batch. The continuous mode is mostly used in the petro-
chemical and bulk chemical industries, whereas the second
one is primarily used in specialty product, pharmaceutical
and biotechnological industries. Furthermore, the semi-con-
tinuous mode (semi-batch) is used also to perform the RD
process.
The concept of combining the important functions of
separation and reaction in a single vessel for overall perfor-
mance is not new to the chemical engineering world. The
recovery of ammonia in the classic Solvay process for soda
ash of the 1860s may be cited as probably the first commer-
cial application of RD. Many old processes have made use
of this concept, such as the production of propylene oxide,
ethylene dichloride, sodium methoxide and various esters of
carboxylic acids (50). Nevertheless, the enormous demand
of methyl tert-butyl ether (MTBE) made this process earn
special attention as a promising multifunctional reactor and
separator.
RD is applied specifically to reversible chemical reac-
tions in the liquid phase, in which reaction equilibrium
limits the conversion of the reactants (51). It has been
proposed as a promising technique for the recovery of lactic
acid with high purity and high yield from fermentation
broths (6) for many reasons, including
● Reduction of equipment costs in esterification, which
normally requires a stage to the reaction and a stage to
the reaction products separation.
● Better conversion of reactants, reducing recycle costs.
● Better selectivity of desired products, reducing by-pro-
ducts formation.
● Significant reduction in catalyst amount required for
the same degree of conversion.
● Heat integration for an exothermic reaction. The heat
of reaction can be used to provide the heat of vapor-
ization and reduce the reboiler duty.
However, there are several constraints and difficulties
according to Towler and Frey (52):
● Volatility constraints. The reagents and products must
have suitable volatility to maintain high concentrations
of reactants and low concentrations of products in the
reaction zone.
LACTIC ACID PURIFICATION 245
● Residence time requirement. If the residence time for
the reaction is long, a large column size and large tray
holdups will be needed and it may be more economical
to use a reactor–separator arrangement.
● Scale up to large flows. It is difficult to design RD
processes for very large flow rates because of liquid
distribution problems in packed RD columns.
● Process conditions mismatch. In some processes, the
optimum conditions of temperature and pressure for
distillation may be far from optimal for reaction and
vice versa.
Despite the difficulties of RD, it has been proposed as a
promising technique because it fulfills the overall objectives
of process intensification (PI). It consists in the development
of innovative apparatuses and techniques that offer drastic
improvements in chemical manufacturing and processing,
substantially decreasing equipment volume, energy con-
sumption or waste formation, and ultimately leading to
cheaper, safer, sustainable technologies (53). As RD is the
most widely applied PI technique nowadays (54) and is
based on many advantages reported for lactic acid recovery,
its use for lactic acid DSP is extremely beneficial.
Reactions to lactic acid recovery
The lactic acid recovery involves two reversible reac-
tions, esterification and hydrolysis, catalyzed by an acid
catalyst, according to the following equations [Eqs. (3)
and (4)]:
Esterification : C3 H6 O3 þ C2 H5 OH $ C5 H10 O3 þ H2 O
Lactic acid þ ethanol $ ethyl lactate þ water
(3)
Hydrolysis : C5 H10 O3 þ H2 O $ C3 H6 O3 þ C2 H5 OH
Ethyl lactate þ water $ lactic acid þ ethanol
(4)
The reaction of esterification or hydrolysis is generally
catalyzed by homogeneous catalyst such as sulfuric acid,
anhydrous hydrogen chloride and many other mineral acids
(51). However, the use of a solid ion-exchange resin as a
catalyst has several advantages over homogeneous catalysts:
low corrosion, ease of separation for the reaction mixture,
no side reactions (55), and can be reused.
Different types of alcohols could be used as reactant in
the esterification reaction, such as ethanol, butanol, metha-
nol and 2-propanol. The use of ethanol as reactant for the
lactate synthesis has the advantage of being produced from
renewable resources. Methanol and butanol are the most
attractive from economic viewpoint (56). The results sug-
gest that for short payback periods, the butanol process is
246 A. KOMESU ET AL.
FIGURE 2 Reactive distillation columns for (a) esterification and (b) hydrolysis.
preferred, while for long payback periods the methanol
process is preferred. The ethanol and 2-propanol processes
are more expensive because an entrainer is required to break
the alcohol/water azeotrope (56).
The volatility of the reactants and products plays an
important role in process design of RD (51). The RD
columns for esterification and hydrolysis are shown in
Figure 2. In the esterification column, lactic acid and alcohol
are fed at the top and bottom, respectively; after the reac-
tion, water is obtained in the distillate and lactate is obtained
in the residue stream. The distillate and residue streams are
fed in the hydrolysis column. Water is fed at the bottom and
lactate is fed at the top of the column. After hydrolysis,
alcohol is recovered at the top, and purified lactic acid is
recovered in the residue.
Reported research
Many studies have reported varying operating parameters
and conditions for lactic acid recovery and purification in
RD. In these processes, lactic acid reacts with alcohols
producing lactate ester, which is hydrolyzed to yield high-
purity lactic acid and alcohol. Patents about RD for lactic
acid recovery and purification have been filed (44, 57, 58).
Seo et al. (51) and Kumar et al. (6) investigated the
recovery of lactic acid in a batch RD column using a
heterogeneous catalyst and feed concentration of 20 wt.%.
Seo et al. (51) studied the effect of operational variables,
such as catalyst loading, reactant mole ratio—lactic acid:
methanol, feed concentration, type of alcohols (methanol,
ethanol and 2-propanol) and partial condenser temperature,
on the yield. The yield of recovered lactic acid was as high
as 90%. In addition, the yield of lactic acid increased as
catalyst loading in the esterification part increased and
reactant mole ratio and feed lactic acid concentration
decreased. Methanol reactant as the lowest boiling point
component gives higher yield than any other alcohol.
Kumar et al. (6) studied the effect of catalyst loading,
mole ratio—lactic acid:methanol, boil-up rate and feed con-
centration. The experimental results indicate that lactic acid
recovery is not influenced by the catalyst loading under the
condition studied, and, at low mole ratio, high recovery of
lactic acid was realized. The recovery of lactic acid
increases with the increase in heat duty. The recovery rate
for 10% feed is greater than that for 20% feed in the initial
period. However, at higher feed concentration (40%), the
recovery rate is much higher. Rao et al. (59) studied the
recovery of lactic acid using batch RD using n-butanol as
reactive entrainer. The yield of recovered lactic acid was as
high as 95% in the operation when all the evaporated water
is condensed and removed from the system.
Continuous reactive separation columns can be used to
recover lactic acid from aqueous lactic acid solution (17, 60,
61). Asthana et al. (60) obtained efficiency higher than 85%
of ethyl lactate and back-conversion higher than 95% of
lactic acid using concentrated lactic acid feedstock (88 wt.
%). Kumar et al. (61) studied a continuous process for the
recovery of lactic acid using a continuous stirred tank reac-
tor (CSTR) and a RD column. In the CSTR, an esterification
reaction occurred between lactic acid and methanol in the
presence of an ion-exchange resin as catalyst to form methyl
lactate and water. The vapor stream of the CSTR containing
methyl lactate, methanol and water was fed to the RD
column. At the top of the column methanol and water
were recovered, and at the bottom concentrated lactic acid
(42.3 wt.%) was obtained. Lunelli et al. (17) studied the
esterification of lactic acid with ethanol in the presence of
heterogeneous catalyst (cation-exchange resin) and
 LACTIC ACID PURIFICATION 247

homogeneous catalyst (sulfuric acid). Factorial designs were
used to identify the influence of operating parameters: reac-
tion temperature, feed molar ratio—ethanol:lactic acid, and
the effect of catalyst type in the process. The best result was
obtained with the feed molar ratio 1.3:1.
A RD with water side draw using both continuous and
semi-batch columns was proposed by Thotla and
Mahajani (62). RD with side draw not only enhances
the conversion level at a given methanol to acid mole
ratio but also avoids possible ester hydrolysis leading to
polymerization and, hence, instability in column opera-
tion. Komesu et al. (63) used a semi-batch RD to study
the lactic acid purification. Factorial experimental design
was used to evaluate the influence of parameters and their
interactions, such as ethanol/lactic acid molar ratio, reboi-
ler temperature and catalyst concentration on yield of
lactate. The results showed that the process for lactic
acid purification proposed in this work provided large
potential to achieve high yield of ethyl lactate (100%)
and lactic acid with 3 times higher concentration than the
raw material.
Mo et al. (45), Edreder et al. (64), Mujtaba et al. (65) and
Aqar et al. (66) studied simulation approaches using com-
mercial simulators, such as Aspen Plus and gPROMS. Mo
et al. (45) studied the hydrolysis of methyl lactate using a
RD column designed based on the total annual costs. The
effects of tray number of rectifying section, tray number of
reactive section and feed location on the total annual cost
were investigated. Edreder et al. (64) studied the optimum
operations of conventional and inverted batch RD columns
undergoing the hydrolysis reaction. For a given column type
and configuration, the minimum operation time was
obtained by optimizing the reflux ratio profile. Mujtaba
et al. (65) studied the thermal energy reduction from the
hydrolysis of methyl lactate and lactic acid separation pro-
cess using reactive batch distillation. The energy minimiza-
tion was achieved by minimizing the production time by
optimizing the reflux ratio, without commitment to product
specification. It was observed that 56% of thermal energy
can be reduced to a product with a certain specification and
lactic acid with 95% purity cannot be obtained with a single
reflux ratio. Aqar et al. (66) studied the esterification of
lactic acid with methanol in conventional and semi-batch
RD columns. The performances of the columns were eval-
uated in terms of minimum batch time and energy consump-
tion for the production of methyl lactate. The results showed
that semi-batch RD columns outperform conventional
columns.
Wide control structures have been developed and tested for
processes to recover lactic acid by esterification and subse-
quent hydrolysis (67). Two processes were considered and
compared: one using methanol and the other using butanol.
The results showed that processes with only a single recycle
stream were somewhat easier to control; for both processes,
responses were more symmetric when temperature control
structures were used.
Table 2 summarizes several studies for lactic acid purifi-
cation using RD processes. Although previous works
achieved high yields of recovery and purification of lactic
acid, they require multiple unit operations. The lactic acid
feed concentration is usually 20 wt.% or higher concentra-
tions, thus a prior concentration of lactic acid produced by
fermentation is necessary. In addition, in most lactic acid
purification studies, lactic acid used as feedstock was pro-
duced by manufacturers. Since a fermentation broth is a
mixture that is more complex than synthetic mixture with
the presence of residual sugars and other organic acids, the
performance of the separation process may be influenced as
reactive distillation is affected by the feed composition.
Additionally, the fermentation impurities may adversely
affect the RD process because it can compete with lactic
acid in the esterification and hydrolysis reactions. Therefore,
new studies for lactic acid recovery by RD using fermenta-
tion broth are required in order to develop a more efficient
and economically attractive process for industrial
applications.

TABLE 2
Lactic acid feedstock and reactive distillation processes for lactic acid purification

LAi LAf
LA feedstock (wt.%) (wt.%) Yield (%) Purification steps Tasks performed Ref.

Commercial 20 NA >90a 1. Batch RD Concentration/purification (51)

Commercial 20 NA 34a 1. Batch RD Concentration/purification (6)
Commercial 40, 60 NA 95a 1. Batch RD Concentration/purification (59)
Commercial 88, 50 and 20 NA >85b 1. Continuous RD Concentration/purification (60)
Commercial 8–10 42.3 80b 1. Evaporator Concentration/purification (61)
2. Reactor
3. Continuous RD
Commercial 120 g L−1 347.68 g L−1 94.8b 1. Semi-batch esteri-fication RD Concentration/purification (63)
2. Semi-batch hydro-lysis RD
Fermentation NA NA 42.82b 1. Continuous RD Concentration/purification (23)

NA, not available; alactic acid; blactate; LAi, lactic acid initial purity; LAf, lactic acid final purity.
248 A. KOMESU ET AL.

Molecular Distillation
The first studies on molecular distillation started during the
1920s in the United States and Europe, with separation of
isotopes of mercury and purification of a high-molecular-
weight non-distillable oil residue (oils of Apiezon) (68, 69).
In Latin America, molecular distillation works were started
in Brazil at the Separation Process Development Laboratory
(School of Chemical Engineering, University of Campinas-
UNICAMP) with Batistella (69) in fine chemicals area and
in further works in lubricating oils and oil fractions (70–72).
The first industrial units of descendent film distillers and
centrifugal film were developed in the 1940s.

Principle of molecular distillation

Molecular distillation or short path distillation is a non-
conventional unit operation of diffusional mass transfer
indicated for separation of homogeneous liquid mixtures
with low volatility, high molecular mass and thermally
sensitive. It is considered as a special case of evaporation
where steam is generated on the liquid surface with the
difference that there is practically no return of gaseous
molecules to the liquid phase (no vapor–liquid equilibrium).
This is achieved by setting the hot evaporation surface and
the cold condensation surface closer to each other than the
mean free path of the evaporated molecules. Therefore, the FIGURE 3 Short path for evaporation and condensation in molecular dis-
tillation. By permission from Pope Scientific, Inc., Saukville, WI, USA (74).
evaporated molecules easily reach the condenser, since the
route is unobstructed (73) as shown in Figure 3. The dis-
tance between the evaporating and condensing surfaces is
typically between 1 and 5 cm (75). In addition, as the
process does not involve the use of a solvent as in extractive
distillation, the product material is not polluted and no
further purification is needed (76).
A molecular distillation apparatus has two possible con-
figurations: with centrifugal (Figure 4) or falling film
(Figure 5). In both designs, the separation principle is the
same: a reduced pressure enables molecules to evaporate
from the hot evaporator to the cold condenser, and the
formation of a thin liquid film promotes effective heat and
mass transfers (79). In centrifugal distiller, the centrifugal
force allows the formation of a thin liquid film that passes
through the heated disk and makes contact with the con-
denser surface (80). The falling film distiller uses gravity
force to promote a thin film on the evaporating cylinder,
usually with a wiping element that mixes and distributes the FIGURE 4 Schematic diagram of the centrifugal molecular distiller. 1.
liquid over the whole evaporator surface (81). Backing/Roughing vacuum pump (chamber); 2. Diffusion (high vacuum)
Molecular distillation is a separation technique used in pump; 3. Rough vacuum pump (degasser); 4. Trap (degasser); 5. Trap
(chamber); 6. Liquid transfer pump; 7. Check valve; 8. Degasser heater;
many purification processes of chemical, petrochemical, oil 9.Rotor heater; 10. Vacuum chamber/condenser; 11. Rotor; 12. Variable
and grease, pharmaceutical and food (82, 83). The applica- speed liquid transfer pump; P: Vacuum pressure gauge. By permission from
tions are varied: recovery of vitamin E from vegetable oils Myers Vacuum, Inc., Kittanning, PA, USA (77).
(8) and petroleum residues (68, 84, 85); separation of bio-oil
(82); obtaining high concentration of monoglycerides (79);
recovery of carotenoids from palm oil (86); and recovery of and mineral oils), studies that involve theoretical aspects,
phytosterols and tocopherols (87), and many others. Besides design and construction of equipment for industrial and
applications in different raw materials (animal, vegetable laboratory scale, determination of operating parameters,

FIGURE 5 Schematic diagram of the falling film molecular distiller. 1.
Engine; 2. Agitation blades; 3. Feeding; 4. Condenser; 5. Falling film; 6.
Evaporator; 7. Residue output; 8. Distillate output; 9. Vacuum system; 10.
and 11. Cooling fluid; 12. and 13. Thermal fluid (78). Reprinted from (78)
with permission from Elsevier.
mathematical models and simulators of molecular distilla-
tion process have also been developed (80, 88–91).
Reported research
Xu et al. (47) studied the recovery and purification of
lactic acid using a molecular distiller. The optimum operat-
ing conditions were found to be the following: pressure of
0.1 Pa, evaporation temperature ranging from 55 °C to 75 °
C, feed flow rate of 90 mL h−1 and stirring speed (wiping
element) ranging from 110 to 130 rpm. Among all the
studied parameters, the evaporation temperature and the
feed flow rate were the most influential on the final purity
of lactic acid, which was higher than 95%.
Wei et al. (92) studied the recovery and purification of lactic
acid, concentrating the solution in a rotary evaporator and then
in a molecular distiller—resulting in purity higher than 96%.
The optimum operating conditions were similar to those of Xu
et al. (47): 0.1 Pa, 55 °C, feed at 90 mL h−1 and stirring at 120
rpm. Under these conditions, lactic acid is obtained in crystal
form (melting point 55 °C).
Chen et al. (7) studied the recovery and purification of
lactic acid by centrifugal molecular distiller using a solvent
extraction step (butyl alcohol) before distillation. The
LACTIC ACID PURIFICATION 249
effects of the evaporator temperature (70–110 °C), operat-
ing pressure (13–66 Pa) and feed rate (15–35 mL h−1) were
evaluated. The optimal parameters were evaporator tem-
perature of 90 °C, operating pressure of 40 Pa and feed
flow rate of 22.25 mL h−1. The lactic acid obtained in these
optimal conditions was 91.6% pure with a 62% yield.
Komesu et al. (93) studied the influence of the operating
conditions, feed flow rate, agitation (wiping element), con-
denser and evaporator temperatures, on residue and distilled
percentages, and lactic acid purity and recovery. Models
were developed in order to describe the response of interest
as a function of these operating conditions. The results
showed that with a high operating pressure (1000 Pa) (in
terms of short path evaporation), and one separation step
89.7% pure lactic acid was obtained.
Yu et al. (94) used molecular distillation following an
association of calcium precipitation and solvent extraction.
The purity and yield of lactic acid were 92.39% and
74.09%, respectively, obtained under the optimal distillation
temperature of 367.1 K (94 °C) and pressure of 24.5 Pa.
The industrial interest in purification of lactic acid by
molecular distillation has been demonstrated by many pub-
lished patents (95–101). Purac Biochem published a method
of industrial-scale purification of lactic acid using molecular
distillation and adiabatic crystallization to form a 95% pure
lactic acid (97–100). Brussels Biotech published a process
comprising the following steps: pretreating a diluted solution
of lactic acid, concentrating and re-concentrating the diluted
solution, and distilling the lactic acid using a molecular dis-
tillation to obtain the purified lactic acid (95, 96). Archer
Daniels Midland Company developed a method comprising
two-step distillation processes (RD and molecular distilla-
tion) for recovering lactic acid and ethyl lactate (101).
Table 3 summarizes several studies for lactic acid purifi-
cation using molecular distillation processes. Based on the
studies reported, it can be concluded that lactic acid is an
excellent candidate for molecular distillation process,
because the lower distillation temperatures and low resi-
dence time reduce lactic acid decomposition giving high
purities and yields. In addition, the many patents reported
showed the industrial interest and potential of molecular
distillation for lactic acid production.
Comparison of Different Production Processes
Lactic acid production in a classical way involves a series of
downstream treatments like precipitation, conventional fil-
tration, acidification, carbon adsorption, evaporation, crys-
tallization and others (4). A typical conventional
fermentation-based lactic acid production process is shown
in Figure 6. The majority of the big lactic acid manufactur-
ing industries like Musashino chemical in Japan, CCA
Biochemical BV of the Netherlands, Natureworks LLC in
the USA use fermentation-based technology (4).
250 A. KOMESU ET AL.

TABLE 3
Lactic acid feedstock and molecular distillation processes for lactic acid purification

LAi LAf Yield

LA feedstock (wt.%) (wt.%) (%) Purification steps Tasks performed Ref.

NA 40–70 >95 75a 1. Molecular distillation III (47)

Fermentation NA >96 NA 1. Rotator evaporator III (92)
2. Molecular distillation
Fermentation 6 91.6 61.73a 1. Filtration I–III (7)
2. Evaporation
3. Centrifugation and evaporation
4. Centrifugation and vacuum filtration
5. Extraction
6. Vacuum distillation
7. Molecular distillation
Fermentation 5 89.7 14.27a 1. Precipitation I–III (93)
55.33 71.49a 2. Centrifugation and vacuum filtration
3. Hybrid short path evaporation
Fermentation 6 92.39 74.09a 1. Precipitation I–III (94)
2. Filtration
3. Rotary evaporator
4. Centrifugation and vacuum filtration
5. Solvent extraction 6. Molecular distillation

NA, not available; alactic acid; blactate; LAi, lactic acid initial purity; LAf, lactic acid final purity; I = Removal of biomass from the broth; II = Precipitation;
III = Concentration/purification.

It is evident from Figure 6 that is necessary a simpler and
cheaper process than typical conventional fermentation-
based lactic acid production process for lactic acid separation
and purification with high-purity and yield. An alternative
process using RD is presented in Figure 7. The advantage of
this process is the few number of separation steps, which
represents reduction in equipment and operational costs. In
addition, RD has other previously discussed advantages that
fulfill the objectives of process intensification (PI). Many
works in the literature studied the purification of lactic acid
using RD, but the economic analysis has been done in only
few works.
Su et al. (56) compared the cost of RD processes using
different alcohols (methanol, ethanol, butanol and isopropyl
alcohol) in order to determine which is preferable from an
economic point of view. The results showed that processes
using methanol and butanol are the most attractive. Joglekar
et al. (2) have done economic evaluation for lactic acid
produced by fermentation using RD combined with differ-
ent downstream processes (reactive extraction, adsorption,
precipitation and electrodialysis). The economical process
was the route with continuous fermentation, reactive extrac-
tion and reactive esterification–hydrolysis. Although it
required slightly higher investments than the precipitation
route and higher unit cost, it did not generate gypsum sludge
(2). RD applications in general show large savings in capital
cost and energy over conventional setups (reactor followed
by distillation) by 20% or more (54).
Another alternative process is described in Figure 8. In
this process, molecular distillation is used for the production
of high-purity lactic acid. Few studies in the literature stu-
died the purification of lactic acid using molecular distilla-
tion, and information about economic analysis of such
processes is not available. Only Lei and Chen (102) showed
a comparison of molecular distillation with ordinary, azeo-
tropic and extractive distillations. Molecular distillation
showed the lower energy consumption and operation com-
plexity, although it is suitable for the lactic acid production
only at low scale due to the requirement of high vacuum.
Among the distillation options, the choice of suitable pro-
cess depends on the specific separation task and economic
considerations (102).
CONCLUSIONS
In this review, it was possible to observe the importance of
lactic acid due to its widespread use and applications, and the
importance of separation and purification technologies for the
establishment of more efficient and cost-effective processes.
The literature reported many lactic acid separation and pur-
ification technologies, but there are some drawbacks that
limit the application of these technologies at industrial
level. Conventional distillation to recover lactic acid from
fermentation has not been acceptable, but converting lactic
acid to esters before being separated by RD is an efficient
alternative technique. Another technology that may be used
for recovery and purification of lactic acid from fermentation
broth is molecular distillation. The lower distillation tempera-
tures and low residence time achieved by molecular
 LACTIC ACID PURIFICATION 251

FIGURE 6 Typical conventional fermentation-based lactic acid production process (4). Reprinted from (4) with permission from Elsevier.

FIGURE 7 Schematic diagram for lactic acid production using reactive distillation.
252 A. KOMESU ET AL.
FIGURE 8 Schematic diagram for lactic acid production using molecular distillation.
distillation makes the lactic acid an excellent candidate for
this separation process. Therefore, reactive and molecular
distillations are efficient and environmental friendly alterna-
tive processes for the separation and purification of lactic acid
from fermentation broth. Although the economic analyses for
reactive and molecular distillation have been done in few
works, the suggested processes showed fewer separation
steps than lactic acid production in a classical way, which
can represent reduction in equipment and operational costs.
Nevertheless, lactic acid produced by fermentation pro-
cess has not been very profitable because of the high cost of
the separation process. To address this problem, it is neces-
sary to develop more efficient and viable separation tech-
nologies to bring out the potential of lactic acid.
FUNDING
The authors are grateful to the financial support from São
Paulo Research Foundation (FAPESP), Project n° 2015/
12783-5.
REFERENCES
1. Dobbin, L. (1931) The Collected Papers of Carl Wilhelm Scheele;
Bell & Sons: London.
2. Joglekar, H.G., Rahman, I., Babu, S., Kulkarni, B.D., and Joshi, A.
(2006) Comparative assessment of downstream processing options for
lactic acid. Sep. Purif. Technol. 52: 1–17.
3. Jong, E., Higson, A., Walsh, P., and Wellisch, M. (2012) Bio-based
chemicals value added products from biorefineries. IEA Bioenergy.
Task 42 Biorefinery.
4. Pal, P., Sikder, J., Roy, S., and Giorno, L. (2009) Process intensifica-
tion in lactic acid production: A review of membrane based processes.
Chem. Eng. Process. 49: 1549–1559.
5. López-Garzón, C.S., and Straathof, A.J.J. (2014) Recovery of car-
boxylic acids produced by fermentation. Biotechnol. Adv. 32: 873–904.
6. Kumar, R., Mahajani, S.M., Nanavati, H., and Noronha, S.B. (2006)
Recovery of lactic acid by batch reactive distillation. J. Chem.
Technol. Biotechnol. 81: 1141–1150.
7. Chen, L., Zeng, A., Dong, H., Li, Q., and Niu, C. (2012) A novel
process for recovery and refining of l-lactic acid from fermentation
broth. Bioresour. Technol. 112: 280–284.
8. Batistella, C.B., Moraes, E.B., Maciel Filho, R., and Maciel, M.R.W.
(2002) Molecular distillation rigorous modeling and simulation for
recovering vitamin E from vegetal oils. Appl. Biochem. Biotechnol.
98–100:1187–1206.
9. Guilherme, A.A., Pinto, G.A.S., and Rodrigues, S. (2009) Avaliação
da produção de ácido lático por Leuconostoc mesenteroides B512F
em xarope de caju. Ciênc. Tecnol. Aliment. 29(4): 738–747.
10. Silveira, M.S. (2009) Utilização do suco de caju clarificado para
produção de ácido lático pelo Lactobacillus casei B-442. Msc
Thesis, Universidade Federal do Ceará, Fortaleza, Brazil (in
Portuguese).
11. Li, Z., Lu, J., Yang, Z., Han, L., and Tan, T. (2012) Utilization of
white rice bran for production of L-lactic acid. Biomass Bioenergy 39:
53–58.
12. Nakano, S., Ugwu, C.U., and Tokiwa, Y. (2012) Efficient production
od D-(-)-lactic acid from broken rice by Lactobacillus delbrueckii
using Ca(OH)2 as a neutralizing agent. Bioresour. Technol. 104:
791–794.
13. Wang, L., Zhao, B., Liu, B., Yu, B., Ma, C., Su, F., Hua, D., Li, Q.,
Ma, Y., and Xu, P. (2010) Efficient production of L-lactic acid from
corncob molasses, a waste byproduct in xylitol production, by a newly
isolated xylose utilizing Bacillus sp. Strain. Bioresour. Technol. 101:
7908–7915.
14. Abdel-Rahman, M.A., Tashiro, Y., and Sonomoto, K. (2011) Lactic
acid production from lignocellulose-derived sugars using lactic acid
bacteria: Overview and limits. J. Biotechnol. 156: 286–301.
15. Li, Y., Shahbazi, A. (2006) Lactic acid recovery from cheese whey
fermentation broth using combined ultrafiltration and nanofiltration
membranes. Appl. Biochem. Biotechnol. 129–132:985–996.
16. Calabia, B.P. and Tokiwa, Y. (2007) Production of D-lactic acid from
sugarcane molasses, sugarcane juice and sugar beet juice by
Lactobacillus delbrueckii. Biotechnol. Lett. 29: 1329–1332.

17. Lunelli, B.H., Atala, D.I.P., Oliveira, N., Wolf Maciel, M.R., and
Maciel Filho, R. (2010) Ethyl lactate production using reactive dis-
tillation: Experimental and simulation. J. Biotechnol. 150: 569.
18. Abdel-Rahman, M.A., Tashiro, Y., and Sonomoto, K. (2013) Recent
advances in lactic acid production by microbial fermentation pro-
cesses. Biotechnol. Adv. 31: 877–902.
19. Vaidya, A.N., Pandey, R.A., Mudliar, S., Suresh Kumar, M.,
Chakrabarti, T., and Devotta, S. (2005) Production and recovery of
lactic acid for polylactide—An overview. Crit. Rev. Env. Sci. Technol.
35: 429–467.
20. Datta, R. and Henry, M. (2006) Lactic acid: Recent advances in
products, processes and technologies-a review. J. Chem. Technol.
Biotechnol. 81: 1119–1129.
21. Galactic. http://www.lactic.com/en-us/products/productrange/galacid
%E2%84%A2.aspx (accessed May 2016).
22. Wankat, P.C. (2007) Equilibrium Staged Separations; 2nd ed. Prentice
Hall: New York.
23. Lunelli, B.H. (2010) Produção e controle da síntese do éster de ácido
acrílico através da fermentação do ácido láctico. Thesis (PhD),
University of Campinas, Campinas, Brazil (in Portuguese).
24. Kumar, S., Mavely, T.R., and Babu, B.V. (2010) Reactive extration of
carboxylic acids (Butyric-, Lactic-, Tartaric-, Itaconic-, Succinic- and
Citric Acids) using tri-n-butylphosphate (TBP) dissolved in 1-dode-
canol and n-octane (1:1 v/v). In International Symposium & 63RD
Annual Session of IICHE in Association with International Partners
(CHEMCON-2010), Annamalai.
25. Eli, B.H. High purity magnesium lactate from steepwater. US Patent
3,429,777, 1969.
26. Kwak, H., Hwang, D.W., Hwang, Y.K., and Chang, J-S. (2012)
Recovery of alkyl lactate from ammonium lactate by an advanced
precipitation process. Sep. Purif. Technol. 93: 25–32.
27. Min, D-J., Choi, K.H., Chang, Y.K., and Kim, J-H. (2011) Effect of
operating parameters on precipitation for recovery of lactic acid from
calcium lactate fermentation broth. Korean J. Chem. Eng. 28(10):
1969–1974.
28. Rauch, M., Gerner, F., and Wecker, A.M. In Ullmanns Encyklopadie
der technischen Chemie, 3rd ed., vol. 12, W. Forest, Weinheim:
Verlag Chemie, 1960.
29. Seader, J.D. and Henley, E.J. (2005) Separation Process Principles,
2nd ed.; Wiley:U.S.A.
30. Alkaya, E., Kaptan, S., Ozkan, L., Uludag-demirer, S., and Demirer,
G.N. (2009) Recovery of acids from anaerobic acidification broth by
liquid–liquid extraction. Chemosphere 77: 1137–1142.
31. Krzyzaniak, A., Leeman, M., Vossebeld, F., Visser, T.J., Schuur, B.,
and Haan, A.B. (2013) Novel extractants for the recovery of fermen-
tation derived lactic acid. Sep. Purif. Technol. 111: 82–89.
32. Matsumoto, M., Takahashi, T., and Fukushima, K. (2003) Synergistic
extraction of lactic acid with alkylamine and tri-nbutylphosphate:
Effects of amines, diluents and temperature. Sep. Purif. Technol. 33:
89–93.
33. Gao, M.T., Shimamura, T., Ishida, N., Nagamori, E., Takahashi, H.,
Uemoto, S., Omasa, T., and Ohtake, H. (2009) Extractive lactic acid
fermentation with tri-ndecylamine as the extractant. Enzyme Microb.
Technol. 44: 350–354.
34. Kurzrock, T. and Weuster-Botz, D. (2010) Recover of succinic acid
from fermentation broth. Biotechnol. Lett. 32: 331–339.
35. Dey, P. and Pal, P. (2013) Modelling and simulation of continuous L
(+) lactic acid production from sugarcane juice in membrane inte-
grated hybrid-reactor system. Biochem. Eng. J. 79: 15–24.
36. Ecker, J., Raab, T., and Harasek, M. (2012) Nanofiltration as key
technology for the separation of LA and AA. J. Membrane Sci. 389:
389–398.
37. Pal, P. and Dey, P. (2013) Process intensification in lactic acid produc-
tion by three stage membrane integrated hybrid reactor system. Chem.
Eng. Process. 64: 1–9.
LACTIC ACID PURIFICATION 253
38. Wang, C., Li, Q., Wang, D., and Xing, J. (2014) Improving the lactic
acid production of Actinobacillus succinogenes by using a novel
fermentation and separation integration system. Process Biochem.
49: 1245–1250.
39. Tugtas, A.E. (2011) Fermentative organic acid production and separa-
tion. Fen Bilimleri Dergisi. 23: 70–82.
40. Filachione, E.M., Lengel, J.H., and Fisher, C.H. (1945) Preparation of
methyl lactate. Ind. Eng. Chem. 37: 388–390.
41. Filachione, E.M. and Fisher, C.H. (1946) Purification of lactic acid.
Ind. Eng. Chem. 38: 228–232.
42. Kumar, H. and Alén, R. (2015) Recovery of aliphatic low-molecular-
mass carboxylic acids from hardwood kraft black liquor. Sep. Purif.
Technol. 142: 293–298.
43. Petlyuk, F.B. (2004) Distillation Theory and Its Application to Optimal
Design of Separation Units; Cambridge University Press:U.S.A.
44. Cockrem, M.C.M. and Johnson, P.D. (1993) Recovery of lactate
esters and lactic acid from fermentation broth. Patent
WO1993000440 A1.
45. Mo, L., Shao-Tong, J.S., Li-Jun, P., Zhi, Z., and Shui-Zhong, L.
(2011) Design and control of reactive distillation for hydrolysis of
methyl lactate. Chem. Eng. Res. Des. 89: 2199–2206.
46. Sanz, M.T., Murga, R., Beltrán, S., and Cabezas, J.L. (2004) Kinetic
study for the reactive system of lactic acid esterification with metha-
nol: Methyl lactate hydrolysis reaction. Ind. Eng. Chem. Res., 43:
2049–2053.
47. Xu, S-L., Zheng, T., and Xu, S-M. (2004) The study of refining
L-Lactic acid by molecular distillation. J. Chem. Eng. Chin. Univ.
18: 246–24.
48. Perry, R.H. and Chilton, C.H. (1999) Chemical Engineers’ Handbook,
7th ed.; Mc-Graw-Hill:U.S.A.
49. Taylor, R. and Krishna, R. (2000) Modelling reactive distillation.
Chem. Eng. Sci. 55: 5183–5229.
50. Sharma, M.M. and Mahajani, S.M. (2002) Reactive distillation: Status
and Future Directions; Wiley-VCH: Weinheim, 3–29.
51. Seo, Y., Hong, W.H., and Hong, T.H. (1999) Effects of operation
variables on the recovery of lactic acid in a batch distillation process
with chemical reactions. Korean J. Chem. Eng, 16: 556–561.
52. Towler, G.P. and Frey, S.J. (2000) Reactive distillation. In Reactive
Separation Processes; Kulprathipanja, S., ed.; Taylor and Francis:
Philadelphia.
53. Stankiewicz, A. and Moulijn, J.A. (2000) Process intensification:
Transforming chemical engineering. Chem. Eng. Prog. 96: 22–34.
54. Harmsen, G.J. (2007) Reactive distillation: The front-runner of industrial
process intensification A full review of commercial applications, research,
scale-up, design and operation. Chem. Eng. Process. 46: 774–780.
55. Helfferich, F. (1962) Ion Exchange; McGraw-Hill: New York, 335–360.
56. Su, C-Y., Yu, C-C., Chien, I-L., and Ward, J.D. (2013) Plant-wide
economic comparison of lactic acid recovery processes by reactive
distillation with different alcohols. Ind. Eng. Chem. Res. 52: 11070–
11083.
57. Dirkzwager, H., Petrus, L., Petrus-Hoogenbosch, C.J.M., and Poveda-
Martinez, P. (2010) Process for reactive distillation of a carboxylic
acid. US Patent 7718039B2.
58. Miller, D.J., Asthana, N., Kolah, A., and Lira, C.T. (2010) Process for
production of organic acid esters. US Patent 7652167B2.
59. Rao, V.V.B., Kumar, P.S., Sailu, C., and Rao, S.R.M. (2014) Recovery
of lactic acid by reactive distillation. J. Appl. Sci. 14 (12): 1289–1293.
60. Asthana, N., Kolah, A., Vu, D.T., Lira, C.T., and Miller, D. (2005) A
continuous reactive separation process for ethyl lactate formation.
Org. Process Res. Dev. 9: 599–607.
61. Kumar, R., Nanavati, H., Noronha, S.B., and Mahajani, S.M. (2006)
A continuous process for the recovery of lactic acid by reactive
distillation. J. Chem. Technol. Biotechnol. 81: 1767–1777.
62. Thotla, S. and Mahajani, S. (2009) Reactive distillation with side
draw. Chem. Eng. Process. 48: 927–937.
254 A. KOMESU ET AL.
63. Komesu, A., Martins, P.F., Lunelli, B.H., Maciel Filho, R., and Wolf
Maciel, M.R. (2015) Lactic acid purification by reactive distillation
system using design of experiments. Chem. Eng. Process. 95: 26–30.
64. Edreder, E.A., Mujtaba, I.M., and Emtir, M. (2011) Optimal operation
of different types of batch reactive distillation columns used for hydro-
lysis of methyl lactate to lactic acid. Chem. Eng. J. 172: 467–475.
65. Mujtaba, I.M., Edreder, E.A., and Emtir, M. (2012) Significant ther-
mal energy reduction in lactic acid production process. Appl. Energy
89: 74–80.
66. Aqar, D.Y., Rahmanian, N., and Mujtaba, I.M. (2016) Methyl lactate
synthesis using batch reactive distillation: Operational challenges and
strategy for enhanced performance. Sep. Purif. Technol. 158: 193–203.
67. Su, C-Y., Yu, C-C., Chien, I-L., and Ward, J.D. (2015) Control of
highly interconnected reactive distillation processes: Purification of
raw lactic acid by esterification and hydrolysis. Ind. Eng. Chem. Res.
54: 6932–6940.
68. Rocha, R.S. (2008) Determinação experimental de correntes do processo
de destilação molecular de resíduos de petróleo e extensão da curva PEV.
Thesis (Msc), University of Campinas, Brazil (in Portuguese).
69. Batistella, CB. (1996) Modelagem e simulação de destiladores mole-
culares de filme descendente e centrífugo. Thesis (Msc), University of
Campinas, Campinas, Brazil (in Portuguese).
70. Sbaite, P.D. (2005) Extensão da Curva de Ponto de Ebulição
Verdadeiro para Petróleos Pesados Nacionais através do Processo de
Destilação Molecular. Thesis (PhD), University of Campinas, Brazil
(in Portuguese).
71. Tovar, L.P. (2008) Purificação do óleo essencial de “Cymbopogon
citratus” para a concentração de citral utilizando a destilação molecu-
lar. Thesis (Msc), University of Campinas, Brazil (in Portuguese).
72. Winter, A., Linan, L.Z., Batistella, C., Maciel, M.R.W., Maciel Filho, R.,
and Medina, L. (2006) Split fraction of basic lubricant oils by falling film
molecular distiller. CHISA 2006. 17th International Congress of Chemical
and Process Engineering, Prague, Czech Republic, 27–31 August.
73. Batistella, C.B. (1999) Tecnologia da Destilação Molecular: da
Modelagem Matemática à Obtenção de Dados Experimentais
Aplicada a Produtos de Química Fina. Thesis (PhD), University of
Campinas, Campinas, Brazil (in Portuguese).
74. Pope Scientific Inc., http://www.popeinc.com/uploads/files/literature/
Bulletin%201.pdf (accessed July 2000).
75. Lutišan, J. and Cvengroš, J. (1995) Mean free path of molecular
distillation. Chem. Eng. J. 56: 39–50.
76. Gorak, A. and Schoenmakers, H. (2014) Distillation: Operation and
applications; Elsevier:United Kingdom.
77. Myers Vacuum Repair Services, Inc., http://www.myers-vacuum.com/
update15/vacuum-stills/pilot-15-centrifugal-distillation-system
(accessed June 2016).
78. Nascimento Lima, N.M., Liñan, L.Z., Manenti, F., Maciel Filho, R.,
Wolf Maciel, M.R., Embiruçu, M., and Medina, L.C. (2011) Fuzzy
cognitive approach of a molecular distillation process. Chem. Eng.
Res. Des. 89: 471–479.
79. Fregolente, L.V., Fregolente, P.B.L., Chicuta, A.M., Batistella, C.B.,
Maciel Filho, R., and Maciel, M.R.W. (2007) Effect of operating
conditions on the concentration of monoglycerides using molecular
distillation. Chem. Eng. Res. Des. 85(A11): 1524–1528.
80. Tovar, L.P., Wolf-Maciel, M.R., Winter, A., Maciel-Filho, R.,
Batistella, C.B., and Medina, L.C. (2013) Centrifugal reactive-mole-
cular distillation from high-boiling-point petroleum fractions. 1.
Mathematical modeling, screening variables, and experimental valida-
tion. Ind. Eng. Chem. Res. 52: 7956–7974.
81. Cvengroš, J., Lutišan, J., and Micov, M. (2000) Feed temperature
influence on the efficiency of a molecular evaporator. Chem. Eng. J.,
78: 61–67.
82. Wang, S., Gu, Y., Liu, Q., Yao, Y., Guo, Z., Luo, Z., and Cen, K.
(2009) Separation of bio-oil molecular distillation. Fuel Process
Technol. 90: 738–745.
83. Sales-Cruz, M. and Gani, R. (2005) Short-Path evaporation for che-
mical product modelling analysis and design. European Symposium
on Computer Aided Process Engineering, vol. 15, 841–846.
84. Winter, A., Batistella, C.B., Wolf Maciel, M.R., Maciel Filho, R.,
Lopes, M.S., and Medina, L.C. (2007) A true boiling point curve
through molecular distillation using framol correlation. 8th
International Conference on Chemical and Process Engineering
(Icheap 8), Gulf of Naples.
85. Maciel, R., Batistella, C.B., Sbaite, P., Winter, A., Vasconcelos, C.J.
G., Maciel, M.R.W., Gomes, A., Medina, L, and Kunert, R. (2006)
Evaluation of atmospheric and vacuum residues using molecular dis-
tillation and optimization. Petrol Sci. Technol. 24: 275–283.
86. Batistella, C.B., Moraes, E.B., Maciel Filho, R., and Wolf-Maciel, M.
R. (2006) Mathematical development for scaling-up of molecular
distillators: Strategy and test with recovering carotenoids from palm
oil. 16th European Symposium on Computer Aided Process
Engineering and 9th International Symposium on Process Systems
Engineering, 1113–1118.
87. Martins, P.F. (2006) Estudos e experimentos para a concentração de
tocoferóis e fitoesteróis por meio da destilação molecular. Thesis
(PhD), University of Campinas, Campinas, Brazil (in Portuguese).
88. Li, Y. and Xu, S-L. (2014) DSMC simulation of vapor flow in
molecular distillation. Vacuum 110: 40–46.
89. Sales-Cruz, M. and Gani, R. (2006) Computer-aided modelling of
short-path evaporation for chemical product purification, analysis
and design. Chem. Eng. Res. Des. 84: 583–594.
90. Lutišan, J., Cvengroš, J., and Micov, M. (2002) Heat and mass
transfer in the evaporating film of a molecular evaporator. Chem.
Eng. J. 85: 225–234.
91. Kawala, Z. and Dakiniewicz, P. (2002) Influence of evaporation space
geometry on rate of distillation in high-vacuum evaporator. Sep. Sci.
Technol. 37: 1877–1895.
92. Wei, Q., Han, Z.W., Ba, I.D.M., Yan, Z.H., and Zhao, X.M. (2004)
Study on recovery and purification of l-lactic acid. Proceedings of the
4th International Conference on Separation Science and Technology:
Frontiers on Separation Science and Technology, Nanning, Guangxi,
China, 717–723.
93. Komesu, A., Martins, P.F., Lunelli, B.H., Oliveira, J., Maciel Filho,
R., and Wolf Maciel, M.R. (2014) Evaluation of lactic acid purifica-
tion from fermentation broth by hybrid short path evaporation using
factorial experimental design. Sep. Purif. Technol. 136: 233–240.
94. Yu J, Zeng A, Yuan X, Zhang X, and Ju J. (2015) Optimizing and
scale-up strategy of molecular distillation for the purification of lactic
acid from fermentation broth. Sep. Sci. Technol. 50: 2518–2524.
95. Van Gansbeghe, F., Bogaert, J.-C., Malhaize, E., Gansberghe, M.V.,
and Wolff, F. (2002) Method for purifying lactic acid. US Patent
6489508 B1.
96. Van Gansbeghe, F., Bogaert, J.-C., Malhaize, E., Gansberghe, M.V.,
and Wolff, F. (1998) Method for purifying lactic acid. Patent
WO1998055442 A1.
97. Van Breugel, J., Van Krieken, J., Baró, A.C., Lancis, J.M.V., and Vila,
M.C. (2002) Method of industrial-scale purification of lactic acid. US
Patent 6630603 B1.
98. Winkelaar, H.M., Breugel, J.V., Vila, M.C., and Lancis, J.M.V. (2008)
Purification of aqueous solutions of organic acids. US Patent 7410556 B1.
99. Winkelaar, H.M., Breugel, J.V., Lancis, J.M.V., and Vila, M.C. (2011)
Purification of aqueous solutions of organic acids. US Patent 7875153 B2.
100. Winkelaar, H.M., Breugel, J.V., Vila, M.C., and Lancis, J.M.V. (2012)
Purification of aqueous solutions of organic acids. US Patent 8192589
B2.
101. Leboreiro, J. (2016) Novel lactic acid recovery process. Patent WO
2016007865 A1.
102. Lei, Z. and Chen, B. (2013) Distillation. Separation and Purification
Technologies in Biorefineries, 1st ed.; John Wiley & Sons, Ltd:United
Kingdom.