Chemical Engineering and Processing 48 (2009) 15491559

Contents lists available at ScienceDirect

Chemical Engineering and Processing:
Process Intensication
j our nal homepage: www. el sevi er . com/ l ocat e/ cep
Process intensication in lactic acid production: A review of membrane based
processes
Parimal Pal
a,
, Jaya Sikder
a
, Swapan Roy
b
, Lidietta Giorno
c
a
Environment and Membrane Technology Laboratory, Department of Chemical Engineering, National Institute of Technology,
Durgapur 713209, India
b
T.D.B. College, University of Burdwan, Burdwan 713347, India
c
Research Institute on Membranes and Modeling of Chemical Reactors, c/o University of Calabria, Via P. Bucci 17/C, 87030 Rende (CS), Italy
a r t i c l e i n f o
Article history:
Received 13 October 2008
Received in revised form 7 July 2009
Accepted 10 September 2009
Available online 16 September 2009
Keywords:
Process intensication
Lactic acid
Clean production
Membrane process
a b s t r a c t
Lactic acid the most widely occurring hydroxy-carboxylic acid has traditionally been used as food
preservative and acidulent. So long, it has been produced through either chemical synthesis route or
fermentation route the latter being the dominating one. Despite its tremendous potential for large scale
production and use in a wide variety of applications, cost-effective production of high purity lactic acid
has remained a challenge for decades, mainly due to high downstream processing cost. In the recent
years, possibility of integration of highly selective membranes with the conventional fermentors has
opened a golden opportunity for full commercial exploitation of the tremendous application potential
of this wonder chemical. This paper discusses recent developments of such membrane-based processes
representing process intensication in production of monomer grade lactic acid while suggesting a very
promising production scheme.
2009 Elsevier B.V. All rights reserved.
1. Introduction
The chemical and the allied process industries all over the world
are now confronted with the big challenges of developing inno-
vative products and processes for survival in an era of emaciated
prot margins amidst highly globalized trade competition and fast
growing environmental constraints. Thus process intensication
throughrevolutionary development of newproducts andprocesses
that ensure reducedmaterial andenergy consumptionandreduced
environmental impacts while offering greater exibility in scale
of operation are the need of the hour. Production of monomer
grade lactic acid (2-hydroxypropanoic acid) a traditionally used
food preservative and acidulent has over the last few decades,
attracted attention of the world researchers.
By virtue of unique presence of both hydroxyl and carboxylic
acid groups, lactic acid can participate in a wide variety of chemical
reactions like esterication, condensation, polymerization, reduc-
tion and substitution and this has contributed to its tremendous
potential as a platformchemical for a whole range of products that
have very large-volume uses for industrial production and con-
sumer products. Biodegradable thermoplastics (polylactic acid),
greensolvents (ethyl, propyl, butyl lactates) andoxygenatedchem-

Corresponding author.
E-mail address: parimalpal2000@yahoo.com (P. Pal).
icals (propylene glycol) are a few examples of lactic acid-derived
products, market demands of which are growing exponentially
over the years [1]. Exploitation of its full 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 down-stream separation
and purication. And this is where; membrane-based processes
are stepping in. Being modular in design, membrane-based pro-
cesses offer great exibility in scale of production depending on
market demand. By virtue of high selectivity, membranes can
ensure high levels of separation and purication. As membranes
of chosen selectivity and permeability can easily be integrated
with conventional fermentors, membrane-based processes permit
simultaneous production and purication in the same unit. This
eliminates the need for separate purication units and results in
compact designwithreducedcapital investment. Membrane-based
separation and purication (barring pervaporation) involves no
phase change ensuring reduced energy consumption. Thus such
processes can meet all the goals of process intensication. In this
paper, we rst briey discuss the traditional processes to high-
light the major problems associated with these processes and then
review the developments in membrane-based processes which
have attempted to overcome the problems of traditional processes.
The objective is to identify an environmentally benign, simple, eco-
nomically viable and continuous manufacturing scheme capable of
producing monomer grade lactic acid with high productivity.
0255-2701/$ see front matter 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.cep.2009.09.003
1550 P. Pal et al. / Chemical Engineering and Processing 48 (2009) 15491559
Fig. 1. Lactic acid production scheme in chemical synthesis route using acetalde-
hyde feed.
2. Traditional production process
Traditionally lactic acid has been produced through either
chemical synthesis route or fermentation route. Chemical synthe-
sis route as shown in Fig. 1 uses by-products like lactonitrile from
other industries. Hydrogen cyanide (HCN) is added to acetaldehyde
(CH
3
CHO) in liquid phase in presence of a base catalyst under
high pressure when lactonitrile is produced. Crude lactonitrile is
then puried by distillation and subsequently hydrolyzed to lac-
tic acid by hydrochloric acid or sulphuric acid [2]. The process
is often dependent on other by-product industries and, consid-
ered expensive where petroleum based raw material is the major
cost-contributor. Moreover, chemical synthesis route produces a
mixture of L-lactic acid and D-lactic acid whereas in most of
the cases, L-lactic acid is the desirable product. The problems of
high cost of raw materials, impurity of the product and depen-
dence on other industries for raw materials could be overcome
in fermentation based process. Thus majority of the big lactic
acid manufacturing industries like Musahino chemical in Japan,
Table 1
Widely used substrates in fermentation-based lactic acid production.
Substrates Reference
Whole-wheat powder [3]
Starch [4]
Cucumber juice [5]
Cheese whey [6]
Sugarcane bagasse cellulose [7]
Molasses [8]
Sugar cane juice [9]
CCA Biochemical BV of the Netherlands, Natureworks LLC etc.
have switched over to fermentation based technology as pre-
sented in Fig. 2. The scheme consists of a number of downstream
treatment schemes like precipitation, conventional ltration, acid-
ication, carbon adsorption, evaporation etc. Though possible
carbon sources may be numerous, mainly the cheap and renew-
able carbohydrates as shown in Table 1 are used as the source
of carbon and produces optically pure form of lactic acid [3]. The
substrates are chosen on the basis of their cost, levels of contam-
inants, fermentation rate, lactic acid yields, by-product formation,
and ability to be fermented with little or no pretreatment and
year round availability. Substrate cost is one of the major cur-
rent problems. Downstream purication needs are closely related
to the nature of these substrates, their degree of conversion and
the reagents or microbes involved in the conversion process along
with other factors. The most widely used substrates for production
of lactic acid are glucose, sucrose and lactose which are soluble
carbohydrates [4]. Cucumber juice (CJ) is also a good substrate for
production of lactic acid as it contains malic acid with glucose and
fructose where malic acid is very rapidly converted to lactic acid.
Molar yield of lactic acid from CJ were found to be 11.2 [5]. Cheese
whey, a by-product from cheese manufacturing industry is also
used as substrate for production of lactic acid as it contains huge
Fig. 2. Typical conventional fermentation-based lactic acid production scheme.
P. Pal et al. / Chemical Engineering and Processing 48 (2009) 15491559 1551
amount of lactose. Composition of this whey permeate is 9899%
total solids, 7981%lactose, 810%ashand2.54%protein[6]. Some
researchers used sugarcane bagasse cellulose for batch lactic acid
production and the yield was 83% but the productivity obtained
was very low(0.93g/L/h) andconcentrationof lactic acidwas 67g/L
[7]. Molasses whichis a byproduct inproductionof cane sugar from
sugar cane juice contains 4060% sucrose have also been used as
a substrate. It has been reported [8] that lactic acid with yield of
0.880.96 and productivity of 4.3g/L could be produced in a 40h-
batch fermentation of molasses with initial sugar concentration of
190g/L. As the molasses contains enough nitrogen source, need for
addition of yeast extract in such case, is eliminated. Timbuntam et
al. [9] used sugar cane juice containing 125g/L sucrose, 8g/L glu-
cose and 6g/L fructose as substrate in a batch fermentation. The
highest yield of 96% was obtained and productivity was 2.8g/L/h at
3%, w/v sugar cane juice after 10h of fermentation. Use of natural
substrates like starch and cellulose is not economically favourable
[10] due to requirement of pretreatment to release fermentable
sugars.
The most widely used homofermentative bacterial strains used
in such fermentation are Lactobacillus bulgaricus, Lactobacillus
Leichmanii, Lactobacillus delbrueckii, Lactobacillus amylophilus
and Lactobacillus plantarum. Fungal strains like Aspergillus niger
and Rhizopus species have also been used in several studies [11]
and have been claimed to be more selective in production of L-
lactic acid stereoisomer and less nutrient-demanding than their
bacterial counter parts. In general, fermentative process can selec-
tively produce the desirable L-lactic acid stereoisomer instead of
a mixture of L and D isomers using specic microbial strains [11]
but maintaining high-growth environment for these microbes is
difcult. With production and accumulation of acid, pH falls and
affects productivity of the microbes. In the conventional fermenta-
tionprocess as showninFig. 2, pHof the batchreactor is maintained
at around 56 by addition of calciumhydroxide or calciumcarbon-
ate and the end-fermentation concentration of lactic acid is only
10wt% normally. Sometimes ammonium hydroxide is also used.
The problem of addition of lime in controlling pH is that it leads
to production of calcium lactate instead of lactic acid at high pH
as pK
a
value of lactic acid is 3.86 at 30

C. Calcium lactate is then

separated fromthe microbial cells by ltration and further puried
by activated carbon adsorption. The subsequent steps are evap-
oration and acidication by sulphuric acid to produce lactic acid
and insoluble calcium sulphate (gypsum) as by-product. Gypsum
by-product whichremains associatedwithorganic mass andis pro-
duced at the rate of 1 metric tonne per metric tonne of lactic acid
is a big environmental problem associated with conventional fer-
mentation process. Need for so many steps along with evaporation
involving phase change to get pure lactic acid naturally involves
high capital investment as well as high operating cost. The prob-
lemof lowpHand hence lowproductivity can be largely overcome
if produced lactic acid is continuously removed from the fermen-
tor and this is possible if fermentation is carried out in a continuous
mode. Continuous removal of lactic acid from fermentation broth
can be done by adsorption [1214], extraction [15,16] and mem-
brane separation. Adsorption and extraction based processes also
need quite a few steps as regeneration of adsorbent and recycling
of solvent is necessary. These processes themselves cannot ensure
separation of microbial cells for their recycle without additional
provision of cell separation and recycle. High cell concentration
in the fermenter is essential for high productivity. Moreover, the
extent of process intensication that can be achieved in a mem-
brane basedprocess due tothe associatedadvantages as mentioned
earlier cannot be expected from adsorption or extraction-based
processes. Thus the recent years have witnessedextensive research
activities on solving the problems of traditional manufacturing
processes through membrane based separations. The subsequent
Fig. 3. Schematic ow diagram of continuous membrane based fermentation sys-
tem coupled with micro, ultra, nano or reverse osmosis membrane module in a
single stage.
sections review the developments in such membrane based
processes.
3. Membrane based processes
For continuous mode operation of a fermentative process using
renewable carbohydrate sources for lactic acid production, the
components that need to be continuously separated from the
fermentation broth are microbial cells, proteins, nutrients (yeast
extract, salts of ammonium, potassium, phosphorus, etc.), uncon-
vertedcarbonsources, water andlactic acidas showninTable2. The
membranes that can play effective role in separation of these com-
ponents are microltration, ultraltration, nanoltration, reverse
osmosis and electrodialysis membranes. Microbial cells and pro-
teins can quickly foul all membranes though extent of fouling
may be far less in microltration membranes compared to that
in nanoltration or reverse osmosis membranes. However, mem-
branes used in some particular modules may be operated for
long without much fouling. Microltration membranes having the
largest pore size (0.10.2m) among the categories can separate
microbial cells for their subsequent recycling to the bioreactor to
ensure high cell concentration and thus high productivity. Ultral-
tration membranes with average pore size much less than that of
the microltration membranes can retain cells and proteins. Sepa-
ration by microltration and ultraltration membranes is based on
size exclusionandfor effective cell harvesting, at least 100300kDa
molecular weight cut off (MWCO) value should be ensured [17] for
this. Nanoltration membranes being in between reverse osmo-
sis and ultraltration membranes with average pore size of 1nm
can separate cells, proteins, nutrients, salts, and unconverted car-
bon sources from lactic acid. Reverse osmosis normally known
as nonporous membrane where separation is based on solution
diffusion mechanism can separate the same components from fer-
mentation broth as nanoltration membranes do but at much
higher operating pressure than what is needed in nanoltration.
The schematic ow diagram in Fig. 3. shows how such micro,
ultra, nano or reverse osmosis membrane modules can be cou-
pled with a fermentor permitting continuous removal of acid from
the broth and separation of cells, nutrients or unconverted car-
bon sources for their subsequent recycle. The scheme in the Fig. 3
shows a single stage integration of a membrane module as has
been investigated in several studies over the last two decades.
Separation and recycle of the components depends on the type
of membrane used. For example, if a microltration membrane
module is coupled, only cells are likely to be retained while per-
mitting acids, unconverted carbon sources, proteins nutrients and
water to pass to the permeate side. This however, ensures con-
tinuous removal of acid from the fermentor helping to arrest
1552 P. Pal et al. / Chemical Engineering and Processing 48 (2009) 15491559
Table 2
Typical components of lactic acid fermentation broth that can be separated by two-stage membrane lters integrated with fermentor.
Components Effects on membrane ux/fouling Separation mechanism
Microbes seriously affects ux of nal lter through fouling microltration with <0.1m lter prior to nal ltration stage
Proteins moderately affects nanoltration ultra/nanoltration in nal stage
Nutrients little effect nanoltration in nal stage
Carbohydrates fouls nanolter recycled through nanoltration in nal stage
Lactic acid does not foul membranes separated out by nanoltration
Water Does not foul membranes volume reduced for concentrated acid
loweringof pH. Despiteseparationof acidcontinuously, manystud-
ies show use of lime or NH
4
OH for adjustment of pH. In a truly
continuous process, such pH adjustment may be redundant. If an
ultraltration membrane module is used in place of microltration
module then proteins along with cells get retained. Nanoltration
or reverse osmosis membrane module can retain all the com-
ponents barring acids and water. Recycling of the components
depend on the types of membranes. The type of pump used for
feeding the membrane module also depends on the types of mem-
branes. For microltration membrane, low pressure (12kgf/cm
2
)
pump may be used. For an ultraltration module, a pump of
36kgf/cm
2
is used. Nanoltration module demands high pres-
sure pump (615kgf/cm
2
) whereas reverse osmosis membrane
system requires still higher pressure (>15kgf/cm
2
) for ltration.
An electrodialysis membrane where separation is based on elec-
tromigration of ions through a stack of cation and anion exchange
membranes basically involves two stepsconventional electrodial-
ysis (CEP) and the bipolar electrodialysis (BED). The rst step (CEP)
separates and concentrates lactate salts and the second step (BED)
converts lactatesalts intolactic acid. Theschematic diagramof Fig. 4
shows lactic acid production in a fermentative process coupled
to electrodialysis membrane modules. The next section reviews
the developments in the rst stage of separation and purica-
tion by microltration and ultraltration membranes and then
moves over to nanoltration, reverse osmosis and electrodialy-
sis.
3.1. Microltration and ultraltration of fermentation broth
Limitations to fermentation based batch production process
basically stems from substrate-product inhibition [18,19] and the
time loss for shut down and start up after every batch of produc-
tion. As the concentration of lactic acid in the fermentation cell
increases above 10g/L, microbial activities start getting reduced
due to increased difculty of survival of the microbes in a low pH
medium. Variation of pH-effects on bacterial growth results from
the presence of dissociated and undissociated forms of lactic acid
in fermentation broth. The undissociated form is more inhibitory
than dissociated form. At low pH (<5) undissociated form domi-
Fig. 4. Schematic diagramof fermentative production of lactic acid integrated with
Micro/Ultra/Nano/RO ltration membrane in the rst stage and Electrodialysis (ED)
membranes in the second stage.
nates andat pH>6, almost complete dissociationof lactic acidtakes
place [20]. Thus the optimum pH value is around 6.
While studying membrane based separation coupled to a fer-
mentor, Milcent et al. [21] observed pH as a key parameter. Apart
from removal of acid from the medium they used NH
4
OH to main-
tain pH at 6.2. Lowering of pH resulted in decrease of ux and vice
versa. But beyond a pHlevel of 78, no further improvement ii ux
was observed with increase of pH. They used a ceramic tubular
microltration membrane (0.1m pore diameter) module for cell
separation and acid removal from the broth of a fermentor. At an
average transmembrane pressure of 1 bar and cross ow velocity
of 4m/s, the systempermitted a steady-state ux of 85L/(m
2
h) for
molasses as carbon source and Lactobacillus delbreuckii ssp. lactis as
microbial strain. It was identied that critical uxes were function
of cross ow velocity. It was observed that increase of cross ow
velocity did not lead to an increase of the ux due to irreversible
fouling resulting fromadsorption of molasses compounds on to the
membrane surface. They did not reuse the separated cells resulting
in low productivity.
Taniguchi et al. [22] observed a rapid decrease in the ratio of
specic growth rate to maximum specic growth (/
m
) at a lac-
tate concentration of 22g/L and no microbial growth was observed
at 35g/L of lactate concentration. At the outset, two most impor-
tant tasks to ensure high productivity in a fermentor are removal
of acid from the fermentor medium to maintain optimum pH
(around 6) and separation and recycle of the microbial cells at the
late-logarithmic growth phase of the microbial cells. Coupling of
membrane separation with a fermentor in an external unit permits
continuous separation and removal of lactic acid from the fermen-
tation broth preventing lowering of medium pH to an inhibition
level and this simultaneously permits cell separation and recycle
also. Taniguchi et al. [22] achieved 29-fold increase (compared to
the system without ltration) by removing lactic acid from the
broth by a cross ow ltration and by recycling the cells retained
on the microlter to the fermentor. This ensured high cell concen-
tration (81.5g dry cell/L) in the fermentor. They used a ceramic
microlter intubular module as showninFig. 5. pHwas maintained
at 6.5 by addition of NH
4
OH. Use of ceramic membranes permitted
easy disinfection also. But ceramic membranes suffer from quick
fouling and can retain only cells where unconverted substrate gets
lost.
Fig. 5. A tubular module with two concentric hollow membrane tubes cast on the
inner and outer walls of two concentric porous support tubes.
P. Pal et al. / Chemical Engineering and Processing 48 (2009) 15491559 1553
In a design aimed at total substrate conversion, Moueddeb et
al. [23] studied conversion of lactose into lactic acid using Lacto-
bacillus rhamnosus in a microltration membrane bioreactor that
consistedof two coaxial alumina tubes having alpha alumina mem-
brane (pore size: 2.010
7
m) on the inner wall of the inner tube
and on the outer wall of the outer tube. The micro-organisms were
xedinthe macroporous support andconnedinthe annular space
of two coaxial porous tubes of a tubular membrane. The substrate
solution was fed into the reactor inner compartment whereas the
liquid percolated in the radial direction across the two membranes.
Lactic acid was produced in the porous space between the two
microltration layers. Though the new design focused on elimi-
nation of bacterial inhibition giving total substrate conversion, ux
decreased rapidly due to membrane plugging by microbes which
could, however, be reduced to some extent by sterilization of the
ceramic membranes.
To eliminate the inhibition problem through direct removal of
acid from the fermentation broth, Giorno et al. [24] integrated one
cross owmembrane module tted with microltration or ultral-
tration capillary membranes with a 2.5L stirred cell. They studied
conversion of glucose to lactic acid using Lactobacillus bulgaricus.
They used capillary polysulfone ultraltration (UF) membranes
of molecular weight cut off diameter (MWCO) of 100kDa and
polyamide UF membrane of MWCOvalue 50kDa. In the same mod-
ule, they tested 0.1m pore size polyamide microltration (MF)
membrane also for separation and recycle of cells from the broth.
With an initial glucose concentration of 17g/L, the achieved lactic
acid concentration was 10.8g/L the average yield being 62% and
productivity, 0.43g/L. Polyamide membranes showed lower ux
reduction than polysulfone types but direct ultraltration of broth
without prior microltration resulted in quick reversible fouling
as the system was operated at cross ow velocity to protect the
microbes from shear.
Compared to polymeric membranes, the ceramic membranes
have the advantage of easy disinfection. Ultraltration membranes
canretainbothcells andproteins. Xavier et al. [25] coupledceramic
ultraltration membrane to a fermentor to separate both cells and
proteins for their recycling and simultaneous removal of acid from
the medium. They achieved 36g/L h productivity and a lactic acid
concentration of 90g/L in a tubular module. In continuous mode of
operation, theuxwas 15L/m
2
h. However, operationof thesystem
for 90h at a dilution rate of 0.40/h ux decreased rapidly due to
clogging of the ultraltration membrane.
As productivity and acid concentration are two mutually exclu-
sive goals infermentative process, achieving bothis a big challenge.
Totake upthis challenge Kwonet al. [26] connectedtwomembrane
cell recycle bioreactors (MCRB) inplate and frame membrane mod-
ule in series with cell recycle in each stage. Fig. 6 shows such a
module. The bioreactor was a water-jacketed stirred glass reactor.
Using Lactobacillus rhamnosus strain on glucose feed stock, they
achieved a high productivity of 57g/L h and lactic acid concentra-
tion of 92g/L. Flat sheet plate and frame module (Fig. 9) is like the
conventional plate and frame lter press where a series of annular
membrane discs can be placed one on either side of polysulfone
support plates that provide channels for withdrawal of permeate.
Spacer plates separate the sandwiches of membranes and sup-
port plated. The spacer plates having central and peripheral holes
direct feedliquor over the membrane surface. Permeate is collected
fromeach membrane pair. Though plate and frame module has the
advantage of easy membrane cleaning option it suffers from the
problem of low membrane surface area per unit volume.
As a hollow ber module shown in Fig. 7 offers high surface
area per unit volume and avoids bypassing of feed unlike in spiral
woundmoduleLeventeet al. [27] integratedanamiconhollowber
microltration membrane (0.1mpore size) module with a biore-
actor. This was a cell recycle system with cell bleeding introduced
Fig. 6. Plate and frame membrane module.
Fig. 7. Hollow ber membrane module.
at the 47th hour when biomass concentration approached 30g/L to
ensure steady state in terms of biomass concentration so that fall in
ux could be arrested. The researchers claimed that for over 100h,
steady state operation could be maintained when ux stabilized at
5L/m
2
h. Theyachieved99%substrateutilizationusingLactobacillus
rhamnosus strain and better purity (economic advantage) by con-
tinuous cell bleeding. However, the study used glucose as feed and
in this case also, pHhad to be maintained by continuous addition of
NaOHwith the help of an automatic pH-stat instrument (Metrohm
system, BrinkmannInstruments, Canada). But their systemsuffered
from high membrane fouling problem also.
To overcome the problem of membrane fouling in microltra-
tionstage, Torang et al. [28] suggesteda shear-enhancedcross-ow
ultraltration module for separation of cells and proteins from
fermentationbroth. 100%proteinretentionwas done by hydropho-
bic (polyethersulfone) membrane (MWCO 25kDa) but due to the
blocking of the pores by protein adsorbed on to the hydrophobic
membrane surface the ux was higher for hydrophilic (regener-
ated cellulose acetate) membrane with MWCO of 20kDa and ux
of 1285L/m
2
h. Hydrophilic membranes used had low protein
binding tendency. The chemical stability and as well as protein
separation was better for hydrophobic membrane so microltra-
tion or centrifugation were suggested before the ultraltration to
make the ultraltration step more efcient by avoiding the fouling
of the membrane by high molecular weight protein. Cell harvest-
ing by microltration or ultraltration for its subsequent recycling
leads to high cell concentration in the fermentor but often exces-
sive build up increases viscosity and causes lowering of ux. To
overcome this problem Crespo et al. [29] suggested cell bleeding.
Nishiwaki and Dunn [30] developed a continuous process for
production of lactic acid by two stage fermentor combined in each
1554 P. Pal et al. / Chemical Engineering and Processing 48 (2009) 15491559
Fig. 8. Cross ow at sheet membrane module.
recycle loop with cell separators and analyzed numerically. The
bleed culture from the rst stage was introduced to the second
fermentor. Byrelatingthemaximumoverall productivitywithdilu-
tion rate it was observed that efciency was greater for two-stage
system. A hybrid cell-recycle ultraltration membrane fermen-
tor system was developed for production of lactic acid. Hollow
ber ultraltration module (Fig. 7) after 61hr operation from the
beginning a second membrane module was introduced and it was
observed that the permeate ux of the second module was higher
than the rst module. These results were explained by the fact
that fouling properties of the fermentation broth during growth
phase of bacteria Streptococcus faecalis were different from the
properties during the non-growing phase. The difference could be
in the protein concentration which was high during the lag phase,
decreases duringtheexponential growthandthestationaryphases,
andremainalmost constant duringthedeathphase. Thecontinuous
fermentation was nished after 83.5h of operation and concentra-
tion, productivity and yield of lactic acid was 16g/L, 0.19g/L h and
0.94g/g respectively using glucose as feed stock. The reversible
fouling was observed due to the need to work at axial velocities
lower than 1m/s.
Xu et al. [31] claimed to have controlled the problemof concen-
trationpolarizationandfoulingeffect bycontrollingtangential ow
in the PVDF microltration membrane (Millipore) attached with a
fermentor for downstream separation of cells Lactobacillus paraca-
sei. They claimed to have achieved a productivity of 31.5g/L h and
yield of 0.85g lactic acid/g glucose. The best results were obtained
that the maximum productivity was 31.5g/L h; yield was 0.85 for
prolonged operation time of over 155h. Operation over such long
periodwas donewithon-linesterilizationandcleaningof themem-
brane using NaOCl and distilled water.
A tubular module (Fig. 5) where the membrane is cast on the
inside of a porous support tube housed in a perforated stainless
steel shroud is considered effective in purication of a solution
having high concentration of solids. A tubular module can also be
operated at high pressure. But normally microltration does not
require highpressure. Another major problemwithtubular module
is quick fouling. Cleaning is often difcult though easy disinfec-
tion of ceramic membrane solves the plugging problems to some
extent. Overall mass transfer area in a tubular module is low and
it involves high volumetric hold up. To overcome the difculty of
fouling and high volumetric hold up, Sikder et al. [32] integrated
a crossow, at sheet membrane module as shown in Fig. 8, with
a fermentor where a laboratory-synthesized polysulfone-cellulose
acetate blend microltration membrane very effectively separated
cells fromfermentation broth without the problemof fouling even
after long hours of operation. The tangential ow pattern in such
at sheet membrane module largely removes concentration polar-
ization problems of dead end lters as shown in Fig. 9. Integration
of ultraltration membrane particularly in tubular module with
Fig. 9. Flat sheet stirred cell operating in dead-end mode.
a fermentor directly in a single step results in rapid fouling of
the membrane due to concentration polarization. In microltration
membranes, this fouling problem is not so acute but in both cases,
integration of either microltration or ultraltration alone results
in huge loss of valuable carbon sources and nutrients though main-
tenance of desired pH level and high cell concentration through
recycling greatly improves productivity overcoming the problemof
pH-inhibition. However, nanoltration and reverse osmosis mem-
branes can retain these unconverted carbon sources and nutrients
for their subsequent recycling along with microbial cells while
simultaneously permitting separation and purication of lactic
acid. The next section reviews the developments in such nanol-
tration (NF) and reverse osmosis (RO) based separations coupled to
a fermentative process.
3.2. Nanoltration and reverse osmosis
Timmer et al. [33,34] integrated NF and RO membranes with a
fermentor. They used a spiral wound module as shown in Fig. 10.
RO or NF membranes were tted with this module for separation
of lactic acid from fermentation broth. The rejection parameters
of NF membranes CA960 and HC95 at a pH of 4.93 for undissoci-
ated and dissociated lactic acid were 0.675, 0.898 and 0.497, 0.953
respectively compared to 0.73, 0.989 and 0.974, 0.998 respectively
in RO membrane varieties CA995 and HR95 at the same pH. But
the mass transfer parameter of NF membranes (CA960 and HC95)
at 4.93 pH for undissociated and dissociated lactic acid was higher
than those of the RO membranes. It was observed that lactic acid
separation characteristics of NF were better than those of ROmem-
branes. As expected, rapidfoulingwas encounteredwhileoperating
the system on either RO or NF membranes.
Liew et al. [35] integrated a polyamide composite membrane
with a stirred cell (Fig. 6) operating in a dead-end mode. For a
250mL reactor, they achieved a ux of 26L/m
2
h lactic acid along
with a ux of 12.5L/m
2
h ammoniumlactate and 7.5L/m
2
h sodium
lactate. The optimum operating pressure was 7MPa and optimum
agitation was found to be 900rpm. The permeate ux is higher
with the at-sheet module than with the spiral wound implies that
spiral wound module is more susceptible to concentration polar-
ization than at-sheet module or the whole membrane area of the
spiral wound module is not effectively used.
To reap the benet of higher ux of a at sheet cross ow
module, Bouchoux et al. [36] integrated such a module (Fig. 8)
of nanoltration membrane (composite polysulfone type Desal 5
DK of GE Osmonics) with a fermentor for production and puri-
cation of lactic acid from glucose. It was observed that glucose
retentiondecreasedinpresence of sodiumlactate. For this decrease
P. Pal et al. / Chemical Engineering and Processing 48 (2009) 15491559 1555
Fig. 10. Typical Spiral wound membrane module.
of retention of glucose, separation was difcult and unachievable.
The decrease of a neutral solute (glucose) retention in the pres-
ence of charged one (sodiumlactate) is probably a general problem
in nanoltration. This can be explained by the charge density of
nanoltration. Higher membrane charge density in presence of
sodium lactate may decrease the glucose retention.
Jeantet et al. [37] integrateda spiral woundnanoltrationmem-
brane module witha fermentor as sucha module has the advantage
of controlling hydrodynamics and concentration polarization to
some extent by changing spacer thickness though membrane sur-
face area per volume is low for this module. Spiral wound module
(Fig. 10) where several at membranes separated by turbulence-
promoting mesh separators form a Swiss role, has long been used
for its compact designallowing a number of modules to be installed
in a single pressure tube and permitting a high operating pres-
sure. In this spiral wound module, concentration effects of ions
were found to be more important than concentration polarization.
Their suggested scheme was for semi continuous production and
separation of lactic acid from the fermentation broth. pH was still
regulated by continuous addition of NaOH. Compared to the pro-
ductivity (typically 1g/L h) of classical batch production system,
they achieved quite high volumetric productivity of 7.1g/L h with
specic productivityof 3.5h
1
. But proteinfoulingof thenanoltra-
tion membrane was high and they suggested microltration prior
to nanoltration as the used spiral wound modules suffered quick
fouling.
In their effort to investigate the effectiveness of mechani-
cally strong membranes, Duke et al. [38] used readily available
-alumina nanoltration membrane and the more advanced
molecular sieve silica membranes, to enrich lactic acid for prod-
uct use by selectively depleting water through the membrane. The
alumina membranes showed initial ux level at 6kg/m
2
h but it
reduced to 1kg/m
2
h after 250min due to pore blocking of lactic
acid. The membrane acted to remove water from the 15wt% feed,
with permeate lactic acid concentration at 2wt% corresponding to
a water selectivity factor of 9. Silica membranes on the other hand
exhibited a water selectivity factor up to 220 (a rejection coef-
cient of 0.995) with lactic acid in the permeate as low as 0.08wt%.
The strong surface charge and wider pore size of the alumina mem-
brane enabled a slowpore blocking mechanism, with ux dropping
towards that of the silica membrane. The silica membrane was
therefore the choice technology as the tight pore spaces inhibited
lactic acid from entering and the charge-neutral surface leading
to a more stable separation not subject to pore blocking. As the
ux of this kind of membrane is very low, commercial application
will need further development in such membranes towards ux
enhancement.
To eliminate the need for frequent membrane replacement,
Polom and Szaniawska [39] used zirconium (IV) hydrous oxide-
polyacrylate dynamically formed NF membranes for production
and purication of lactic acid from waste lactose. Though such
membranes were foundtoretaintheir mechanical strengthfor long
duration, the associated ux was low and cost of such membranes
is still high. In this investigation they observed higher electrolyte
rejection with increasing pH.
A combined process of nanoltration and reverse osmosis was
developed by Li et al. [40] for separation and concentration of lac-
tic acid from cheese whey fermentation broth. Five NF membrane
(CK, DK, DL, HL, and GE) and two reverse osmosis membrane (DS
11 AG and ADF) were tested at different pressures. Highest lac-
tose retention (971%) was obtained by HL NF membrane with
a moderate permeate ux of 33.0L/m
2
h compared to DK and DL
membrane (lactose retention were 88.2% and 69.8% respectively)
but the lactic acid retention was also high 43.7% (compared with
retention of 38% and 26.1% with other membranes) for this type of
membrane which was not desirable. Permeate ux was increased
with increasing pressure. After nanoltration reverse osmosis was
applied to concentrate lactic acid. 100% lactic acid retention was
achieved at 5.5MPa pressure for ADF membrane compared to
DS11 AG membrane 96% at the same pressure. In this case also,
membranes suffered quick fouling in absence of prior ltration of
cells.
3.3. Electrodialysis
Fermentation based process requires maintenance of near neu-
tral pHfor high productivity and this necessitates addition of alkali
in most of the cases. Alkali addition produces salt of lactic acid
instead of lactic acid itself. To overcome this salt problem, electro-
dialysis basedprocesses that donot require additionof acidor alkali
again to convert lactate salts into lactic acid have attracted atten-
tion of several researchers. The problem of disposal of by-product
gypsumassociated with conventional fermentation process can be
largely overcome through electrodialysis. Datta et al. [41] studied
the advantages associated with such electrodialysis process.
Fig. 11. Typical electrodialysis cell conguration.
1556 P. Pal et al. / Chemical Engineering and Processing 48 (2009) 15491559
Electrodialysis technology a scheme of which is shown in Fig. 11
is based on electromigration of ions through a stack of cation and
anion exchange membranes. Basically, it involves two steps. The
rst step called conventional electrodialysis (CED) separates and
concentrates lactate salts. The second step called bipolar electro-
dialysis (BED) converts lactate salts into lactic acid.
Habova et al. [42] has described such a two-stage electrodialy-
sis process for concentration of sodium lactate from fermentation
broth in the rst stage and its subsequent electroconversion into
lactic acid in the second stage. They achieved 151g/L of lactic acid
in the nal stage.
Lee et al. [43] integrated an electrodialysis unit consisting of
5 pairs of cation and anion exchange Neosepta membranes with
a fermentor (3.7L stirred) for production of lactic acid from corn
steep liquor (CSL) using lactobacillus strain.
Mathieu Bailly [44] studied performance of electrodialysis with
bipolar membranes (EDBM) in connection with an industrial unit.
He has given the economics of such a plant and claimed that envi-
ronmental impact of such a plant is low.
Efcient electrodialysis needs cell free lactic acid. Thus litera-
ture shows many such studies that include micro ltration, ultra
ltration or nanoltration prior to electrodialysis.
Danner et al. [45] developedanultra-ltrationmembrane biore-
actor coupled with on-line monopolar electrodialysis to recover,
pre-purify and concentrate lactate. They started on-line electro-
dialysis of the ultraltration permeates after 159h of cultivation
and the fermentation was completed at 1052h without any micro-
bial contamination. But thevolumetric productivity(1.38g/L h) was
low and lactic acid concentration was 35g/L with maximum yield
of 0.80.
Reimann [46] integrated ultraltration, softening, electrodialy-
sis, ionexchange andevaporationsteps witha fermentor toachieve
99% removal of impurities from lactic acid and a free lactic acid
concentration of 183g/L. But the process is still cumbersome and
involves high cost due to so many steps.
Intolerance to multivalent ions is a problemwith electrodialysis
membranes.
Bouchoux et al. [36] observed that at sheet cross ow NF
membrane module prior to electrodialysis was quite efcient
in separation of calcium and magnesium ions from lactic acid
fermentation broth. Magnesium and calcium rejections were
647 and 727%, respectively and lactate recovery rate reached
252mol/m/h for P=20bar.
Energy consumption associated with ED processes if normally
high and to make the economically attractive attempts have been
made to increase energy efciency. A modied two-phase eletro-
electrodialysys (MTPEED) process developed by Yi et al. [47]
showed a strong potential in the recovery and concentration of
lactic acid without generating salt waste compared to EED pro-
cess. The process was more effective and more economic. The
current efciency was 100% for MTPEED process compared to EED
process having 68.2% and the specic energy consumption was
lower 1.404kWh/kg than EED process 1.956kWh/kg at current
density 160.7A/m
2
. The cell voltage was depending on phase ratio
of organic phase towater phase andlower phase ratiowas desirable
for MTPEED. The electro-electrodialyzer made of PTFE is divided
into one cathode compartment and one anode compartment by an
anion- exchange membrane of 0.005m thickness and 0.0056m
2
surface area.
Though several studies have been undertaken to establish the
potential of bipolar electrodialysis as an efcient and eco-friendly
method of lactic acid production, concentration and purication,
commercialization of bipolar membrane itself has been done in
very limited cases and electrodialysis fermentation (EDF) for lac-
tic acid has hardly been commercialized. Due to poor conductivity
of the organic phase power consumption in electrodialysis process
is always high.
4. Integrated membrane processes
The situation improved when UF of the broth was done prior
to nanoltration or reverse osmosis. Gonzalez et al. [48] recovered
lactic acidfromultralteredwheybytwotypes of membranes - spi-
ral wound DK2540C and tubular AFC80 nanoltration membranes.
Lactic acid transport was strongly affected by pH. At increasing pH,
lactate retention was higher but the permeate ux decreased. For
a constant permeate ux of 60L/m
2
h in the pH range of 6.0, DK
membranes achieved a lactate rejection of 1091% whereas for AFC
membranes, rejection was 4582% as the molecular weight cut-off
was higher in DK membranes.
US Patent [49] claimed to develop a membrane-integrated pro-
cess that integrates one ceramic tubular UF module in the rst
stage cell separation fromfermentation broth and NF in the second
stage for lactic acid separation. The second stage module is a spiral
wound type. The process claims to achieve high cell concentration
510
9
CFU/mL. Ammonium lactate produced does not precipitate
allowing ltration and continuous removal. Lactic acid concentra-
tion of 12wt% is attained using lactobacillus strain on saccharied
mash of grain as carbon source.
To ensure long term operation without membrane fouling
Tejayadi and Cheryan [50] integrated hollow-ber (Fig. 5) ultra-
ltration module for clarication and cell recycling and a reverse
osmosis system for preconcentrating whey permeates with a fer-
mentor. Thus productivity was 22.5g/L h with a yield of 0.89 in this
Table 3
Comparative cost factors of some lactic acid production processes.
Process Major cost factors Major merits/demerits Reference
Conventional fermentation multiple operation xed capital, labor,
energy, maintenance and chemical cost
Operation cost is 50% of the total cost
low raw material cost, gives highly pure
product form but not a clean technology,
generates 1 ton waste/ton acid
[1]
Chemical synthesis process High feed and Equipment cost fails to yield pure product and not a clean
technology
[2]
RO-integrated fermentation RO membrane cost 28% of xed cost high productivity of 22.5g/L/h Clean
technology
[26]
Electrodialysis-integrated fermentation multiple operation involving 80% of
total cost for 70% conc. acid, cost US$
1.15/ton (in 2000)
Clean technology pure product [3]
UF, RO, Ion-exchange-Integrated fermentation Concentration and fermentation
involved 40% and 47% of total cost
respectively for 50% conc. acid
Cost US$ 1.25/kg (in 2007)
Clean technology, pure product [51]
RO, NF-integrated fermentation Except membrane cost, other cost
factors on energy, labor, equipment are
very low
Clean technology, high productivity and purity [52,53]
P. Pal et al. / Chemical Engineering and Processing 48 (2009) 15491559 1557
membrane recycle fermentor and the concentration of lactate was
89g/L obtained in 150h of operation. But the membrane units con-
tributed about 28% of the total xed capital costs. However there
are some adverse effects of this lactate on the performance of RO.
Majority of the research efforts have been directed towards
production of high purity lactic acid in fermentative process with
automatic or manual control of pH through addition of NaOH,
Ca(OH)
2
or NH
4
OH resulting in production of lactate salts instead
of lactic acid directly. This necessitated concentration and conver-
sion of lactate salts into lactic acid through further processing like
extraction, evaporation, precipitationfollowedbyacidication, and
electrodialysis. Suchdownstreamprocessing steps not only involve
high energy requirement but add to overall production cost. Com-
parison of major cost factors associated with a traditional process
vis--vis the membrane basedprocesses as showninTable 3clearly
establishes edge of the latter over the former mainly on account
of downstream processing costs and raw material cost. Table 3
also shows that membrane based processes represent clean tech-
nology as need for multiple steps along with many chemicals of
the conventional processes is eliminated. High productivity in a
continuous membrane based process adds to the economy of the
process. As membranes with high selectivity can be manufactured
and used in compact modular designs, high purity of the product is
ensured in a membrane integrated process. Membrane integrated
processes are also better than conventional processes in terms of
energy consumption and labour costs as the plants are compact
involving only a very few steps and no phase change is involved.
However, Table 3 shows that multiple operations are involved in
electrodialysis based process and 80% of the total cost is due these
operations. In UF, RO and ion-exchange processes, very dilute lac-
tic acid is produced and hence concentration involves 4050% of
the total cost. Though the major cost contributor in a membrane
based process is the membrane, these costs are likely to come
down with development of membranes with better mechanical
strength and antifouling characteristics. This indicates potential
scope of process intensication through integration of membranes
with conventional fermentative process. Integration of micro or
ultraltration membranes mostly in tubular, hollow ber or spiral
wound modules with fermentor have been done for cell separa-
tion and recycle. Direct reverse osmosis or nanoltration of cell
free broth for separation and purication of lactic acid have been
investigated in very few studies. Economic evaluation has been
done for certain categories of schemes which have unnecessarily
relied heavily on some specic feedstock involving cumbersome
processing. An exhaustive evaluation considering both fermenta-
tive conventional as well as fully membrane-integrated processes
for separation of both cells and lactic acid is desired to help choose
the best production scheme. Efforts should be directed towards
developing a fully membrane-integrated fermentative process for
operation in continuous mode with continuous cell separation and
recycle and continuous separation of lactic acid directly as perme-
ate of a properly selectednanoltrationmodule that overcomes the
problem membrane fouling. Thus the scheme presented in Fig. 12
could be one such membrane-integrated continuous production
scheme having the potential of achieving the major goals of process
intensication in lactic acid manufacturing.
5. Economic evaluation of lactic acid production in
membrane-integrated processes
The conventional fermentative process of lactic acid production
involves a series of steps like precipitation, ltration, acidication,
carbon adsorption, evaporation and crystallization and 50% of the
cost of lactic acid manufacture is consumed in these processing
steps. Moreover, 1tonne CaSO
4
is generated as solid waste per ton
of lactic acid produced. Thus the conventional process is neither
economic nor environmentallybenign. Manyintegratedmembrane
systems have been studied for the production of lactic acid but the
economic analysis has been done in few studies.
While studying the techno-economic feasibility of a membrane
recycle fermentor, Tejayadi and Cheryan [50] have given the cost
break up which shows that for a 89g/L concentrated lactic acid
with a productivity of 22.5g/L h and yield of 0.89, cost component
for the RO membrane unit constitutes about 28% of the xed cost
and 5% of the total operating cost. The two largest costs were whey
transportation cost (35%) and yeast extract cost (38%). To minimize
thewheytransportationcost, theysuggestedlocatingthelactic acid
plant within the cheese plant itself.
Akerberg et al. [3] have done an economic evaluation of lac-
tic acid production from whole-wheat our consisting of starch
and bran containing nutrients. They compared production costs for
70% concentrated lactic acid in a 3X10
4
tonnes/year capacity plant
under different production schemes with the purpose of identify-
ing the bottlenecks of production. They observed that operational
cost contributed80%of the total cost andthe major operational cost
components were rawmaterial, saccharication, fermentation and
electrodialysis. Lactic acid production cost per kg was found to be
around US$ 1.101.15 in 2000. But most of the cost components
are very much raw material-specic and scheme-specic whereas
a number of better production schemes and better raw material
options are available.
An integrated process for production and purication of lactic
acid by fermentation was economically evaluated by Gonzalez et
al. [51]. They arrived at a calculated annual cost of US$ 1.25/kg
for 50% concentrated lactic acid. The integrated process consisted
of fermentation, ultraltration, ion-exchange, reverse osmosis and
vacuum evaporation steps. It was observed that 40% of the total
cost was contributed by concentration step alone whereas the
largest cost component (47% of the total cost) was fermentation
cost. Concentration step involved high cost due to depreciation
of the equipment (41%) and the main cost contribution in clari-
cation by ultraltration came from replacement cost of ceramic
membrane. The total annual cost was high in fermentation pro-
cess 52% followed by ion exchange process 27%. In fermentation
step, cost of the yeast extract used as supplement was high (54%)
and it could be reduced by using other supplement like whey pro-
teins but the productivity was lowin that case. Cost of yeast extract
could be reduced by operating in continuous mode and recycling
the biomass and protein to the reactor so that productivity would
Fig. 12. A promising continuous fermentative lactic acid production scheme with
two-stage integration of membranes representing high process intensication
1558 P. Pal et al. / Chemical Engineering and Processing 48 (2009) 15491559
also increase. In the ion exchange process, resin regeneration cost
(91%) was the highest. Vick Roy [52], Timmer et al. [53] have shown
that continuous production of lactic acid in cell recycle fermentor
were economically favourable.
Preliminary economic evaluation for a 1000tonnes/year plant
for four different production schemes- reactive extraction (non-
membrane and batch fermentation), ion exchange and adsorption
(non-membrane, continuous fermentation), conventional batch
fermentation (non-membrane and calcium lactate precipitation
type) and monopolar and bipolar electrodialysis can also be found
in Jogelekar et al. [54]. But they largely bypass the membrane-
integrated processes that represent high process intensication.
6. Conclusion
In view of the soaring demand of lactic acid in the market, mul-
titude of research activities have been carried out for production of
lactic acid in fermentative process using cheap, renewable carbon
sources. In several membrane based studies, successful separation
of the components of fermentation broth by micro, ultra, nano, and
reverse osmosis and electrodialysis membranes has been demon-
strated. However, integration of such membranes with a fermentor
ina single stage has failedto achieve all the goals of process intensi-
cationinlactic acidmanufacturing. Ajudicious combinationof the
types of membranes andthe modules has the potential of achieving
these goals. It appears that integrationof microltrationmembrane
in the rst stage followed by a nanoltration membrane in the
secondstageinaat sheet cross owmodulecanhelpreachthetar-
gets of commercial production of monomer grade lactic acid with
high productivity and concentration in an environmentally benign
process. Such a system should be studied in detail for scale up.
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