Potential and assessment of lactic acid production and isolation – a review

Jantasee Sasiradeea,*, Marlene Kienbergerb, Mungma Nuttakulb, Matthäus Siebenhoferb

a
Department of Chemical Engineering, Faculty of Engineering, Rajamangala

University of Technology Thanyaburi, Pathum Thani 12110, Thailand

b
Institute of Chemical Engineering and Environmental Technology, Graz University
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of Technology, Inffeldgasse 25C, Graz 8010, Austria

* Corresponding author: Jantasee Sasiradee, Address, Tel: +66-254-94613; E-mail:

sasiradee.j@en.rmutt.ac.th

Abstract

The majority of commodity plastics is made from petroleum-based chemicals.

Lactic acid serves as a monomer for the production of the biodegradable polymer

poly lactic acid. This paper provides a review on the state of the art production and

isolation process for lactic acid. Problems in the production and isolation have been

identified, the relevant results in optimized production are presented in the first part

of the paper. In the second part a decision matrix is used as a guideline for the

discussion on the state of research in the isolation and purification of lactic acid.

Mechanical unit operations, mass transfer unit operations, reactive separation

techniques and process combinations are reported in the literature. At the end an

economic evaluation of isolation processes such as conventional precipitation,

reactive membrane separation, and reactive distillation are presented.

Keywords:

Lactic acid, Lactic acid production, isolation, downstream processing

This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which
may lead to differences between this version and the Version of Record. Please cite this
article as doi: 10.1002/jctb.5237

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 Introduction

The worldwide consumption of lactic acid in 2012 was 259.000 tons/a and in

2015 330.000 tons/a.1,2 According to Global Industry Analysts, Inc. report, in 2017

the total demand of lactic acid is expected to be 367.300 tons/a.3,4 Due to the broad
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range of applications of lactic acid, such as food, beverages, cosmetics,

pharmaceuticals and the chemical industry, the demand of lactic acid is increasing

continuously.5 Lactic acid is generally recognized as safe (GRAS) for the use as food

additive by the US food and drug administration, therefore it can be applied in food-

related industrial application as an acidulant, as preservative and/or as pH regulator.

The significant increase of lactic acid demand is related to the use of lactic acid as

monomer for the production of poly lactic acid (PLA). Around 95% of current PLA

production capacity is covered by Natureworks LLC, they are also the major

manufacturers for fermentative lactic acid.1

Lactic acid is synthesized chemically or by fermentation. Sustainable

production of lactic acid in industrial scale by microbial fermentation of renewable

raw material and value added waste, together with biorefinery technologies,

presented in Figure 1, has attained much attention. Currently, over 90% of the global

lactic acid production is made by the microbial fermentation.6 This process route has

become a promising alternative because of the benefits in terms of the

environmental concerns, the renewable feedstock utilization, the low energy

requirement and high product purity (> 95%).7

However, the production of lactic acid by the microbial fermentation faces

many challenges. Firstly, the lactic acid fermentation is an end-product inhibition

process. The inhibition of lactic acid generation is caused by the product itself due to

lowering the pH-value of the broth. A mixture of neutralizing agent and acidifying

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 agent is required for pH-control of the fermentation and hydrolysis. The costs of the

neutralizing agent, the acidifying agent, and the byproduct disposal have to be

considered. Secondly, the cost of nutrients for microoganisms has to be considered.

Various kinds of nutrients namely nitrogen carriers, vitamins, and minerals are
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needed for lactic acid production; yeast extract is of special interest as this is the

most efficient nutrient, but also costly. Much economic attention has been paid to a

low-cost alternative for the replacement of traditional nutrient sources. Thirdly, the

cost of lactic acid isolation from fermentation broth is currently and historically high

because the low volatility of lactic acid and strong affinity to water cause difficulties in

the isolation process. In order to overcome these challenges, the total bio-based

lactic acid production cost should be minimized, special attention has to be set on

the isolation cost, which contribute with approximately 50% to the overall lactic acid

production cost.8

State of art production and alternative technologies

Production of lactic acid

The major chemical process for lactic acid production is the hydrolysis of

lactronitrile with a strong acid, which produces acrylonitrile as a by-product. The

lactic acid is purified by esterification with methanol to produce methyl lactate, which

finally is hydrolyzed to form pure lactic acid in acidic aqueous solution. Chemical

synthesis of lactic acid requires several highly pure chemicals such as lactronitrile

and sulfuric acid, which substantially affect the production costs. Furthermore,

chemically produced lactic acid leads to a racemic mixture of DL-lactic acid.9 Using

the optically pure L(+) or pure D(-) lactic acid as monomer results in a high

crystalline PLA with a higher melting point compared to PLA produced from a

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 racemic mixture.10,11 Pure D(-) and L(+) lactic acid can be synthesized via

fermentation, and it is a human metabolite.12

The fermentation process is carried out in different ways, namely batch, fed-

batch, continuous and repeated process, depending on substrate types,

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microorganism species, microbial growth and viscosity of the fermentation broth.

Because of product inhibition, the fermentation process has to be operated at pH-

values between 5 and 7, and in a temperature range of 25 – 60 ºC depending on the

microorganisms catagorized.1,5,13 Fermentation is most commonly operated in batch

mode because the closed system in batch operation avoids contamination with

undesired microbes in the fermentation broth and provides higher lactic acid

concentration than other fermentation processes.13,14 However, undissociated and

dissociated lactic acid can inhibit the bacteria cell growth.15,16 Lactic acid is able to

dissociate and release protons resulting in increasing the acidity of the cytoplasm,

the undissociated form of lactic acid can freely diffuse into the bacteria cell

membrane affecting the cell metabolism. The cells consume much energy to

maintain an internal pH constant causing cell growth rate inhibition and hence lactic

acid production rate.17,18 The undissociated form of lactic acid is a more effective

inhibitor, due to more specific inhibition of several metabolic and anabolic

function.2,19 Thus, neutralizing agents, such as sodium hydroxide, calcium hydroxide

or calcium carbonate, are added to the batch during the process to adjust the pH-

value during fermentation. The neutralizing agent reacts with the undissociated lactic

acid formed during fermentation, to form lactate, which is less harmful to the

microorganisms. Different batch fermentation methods have been evolved including

separate hydrolysis and fermentation (SHF) and simultaneous saccharification and

fermentation (SSF).20 Due to the separation of the hydrolysis step and the

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 fermentation step the SHF process requires higher enzyme load in order to

effectively finish the two-step process. In comparison, the SSF process combines the

enzymatic hydrolysis of polysaccharide to glucose and xylose with the lactic acid

fermentation process. In terms of single step production, short process time, less
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product inhibition and increased productivity the SSF is more effective than the

SHF.1,7

In fed-batch fermentation, the substrate is fed continuously into the

fermentation broth without removal of the broth. Cell growth and subsequently the

productivity are controlled via continuous substrate feeding. In fed-batch operation

the feeding method, feeding concentration as well as the rate of feeding are

challenging procedures. Typically, the fermentation is carried out in chemostat

(CSTR) fermenters, where the rate of medium flow is controlled to keep the culture

volume constant.21 Finally, repeated fermentation refers to the repeating cycle of

cells from previous fermentations, feeding the cells into the next fermentation either

in batch or fed-batch operation. This process requires additional equipment to

recover the cell broth, such as centrifuges or filters. The benefits of this process are

an increased yield as well as savings in time and labor cost.1

State of the art lactic acid bacteria (LAB) in commercial application are

Lactobacillus strains, these bacteria are used because of their ability to produce

lactic acid with high yield, high productivity, and high selectivity of pure D(-) or L(+)

lactic acid isomers.7,22 One of the major drawbacks of these strains is their

requirement for complex nutrients, leading to higher efforts in lactic acid separation

and purification processes. There are other interesting LAB strains with promising

characteristics available. For example, Bacillus strains require low amount of

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 nitrogen source to produce lactic acid. The bacillus strains can grow and produce

lactic acid by using mineral salt medium.5,23

Purification of lactic acid

Owing to the presence of various impurities in the fermentation broth, low

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vapor pressure of lactic acid and its tendency to self-polymerization, the purification

of lactic acid is a technological challenge. The conventional purification process for

lactic acid, obtained from fermentation, are precipitation24,25, extraction24,26, as well

as esterification and distillation27. For the precipitation process, the fermentation

broth is heated to approximately 70 ºC to kill bacteria; microorganisms are then

separated from the broth by centrifugation or filtration.25,28 Then, the lactic acid in

form of calcium lactate is acidified with a strong acid to form calcium sulfate, which is

a low-value byproduct29 and the undissociated lactic acid. Colorants are removed

from the solution with activated carbon. The lactic acid in the remaining solution is

then purified and concentrated via the combination of several methods, including

extraction with an appropriate solvent, ion-exchange, adsorption onto a suitable

support followed by desorption or electrodialysis.25,30,31 The purification of lactic acid

by the precipitation consumes high amount of sulfuric acid, and it produces large

quantities of solid waste, leading to high cost of chemicals and waste disposal.

Moreover, the optical purity can suffer during the purification process because

isomerization of lactic acid may occur. Thus, its purity does not suffice the needs for

pharmaceutical applications or polymer synthesis any more.

To avoid calcium sulfate formation, further industrial-scale processes for lactic

acid purification from fermentation broth have been developed. In situ recovery of

lactic acid via liquid-liquid extraction with different solvents, such as water-insoluble

amines (e.g., tri-n-octylamine)32,33, quaternary ammonium salts (eg.,

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 Tri(C8C10)methylammoniumchloride [Aliquat 336])34,35, ester (e.g., tri-n-butyl

phosphate)34, or ketone (e.g., methyl isobutyl ketone)34, is common. Due to high

efficiency and selectivity as well as poor solubility in the aqueous phase tertiary

amines with a long-hydrocarbon chain have been found to be appropriate extractants

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for the separation of lactic acid.21,34,36 The fermentation broth is contacted with the

extractant at temperatures from 15 ºC to 60 ºC and atmospheric pressure. Lactic

acid is extracted into the solvent phase followed by back extraction with water at

temperatures from 90 ºC to 160 ºC and a pressure of 2.1 hPa, leading to selective

transfer of lactic acid into the aqueous stripping phase.37 The phase equilibrium is

pH dependent, with ongoing process time and hence decreasing pH-value

decreasing extraction efficiency is observed.38 For pre-concentration of the lactic

acid the water is removed via evaporation or distillation. In order to prevent lactic

acid dimerization and oligomerization, the distillation process shall be performed

under vacuum.37

A large-scale process for the purification of lactic acid has been carried out by

distillation under appropriate operating conditions respectively via combination of

esterification reaction and distillation. Lactic acid, present in the fermentation broth,

reacts with alcohol to the respective ester, followed by distillation to separate the

ester from the fermentation broth and from impurities. Via hydrolysis the lactic acid is

converted into the pure form; the alcohol has to be separated. However, the

combination of esterification and distillation requires large amount of energy to obtain

highly purified lactic acid. Literature reported that the low volatility of lactic acid with

its affinity to water causes problems in direct distillation, and when concentration of

lactic acid is more than 80%, it highly inclines to self-polymerization.39 The purity of

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 lactic acid can be enhanced by means of steam distillation in vacuum. Lactic acid

produced via this process route can be used in pharmaceutical applications.40

Some non-technical barriers also affect industrial scale production of lactic

acid in the biorefinery. The main non-technical barriers are still associated with
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economics. The lack of reliable information on environmental and ecological impact

of changes in the production process is another factor which retards implementation

of new process technologies.41

Approach on problem solving

Main obstacles in the lactic acid production are the cost of the chemicals in

fermentation process, the cost of the raw materials (microorganisms and nutrients),

as well as isolation and purification processes. Furthermore, the production should

be concerned for environmental protection since at COP2015 in Paris,42 195

countries agreed on reducing global warming to well below 2°C. Hence, there is a

need to intensify the lactic acid production processes respectively develop novel

process routes. For the lactic acid production, this topic is addressed via the use of

different microorganisms. Algae, which are photosynthetic microorganisms, can

convert starchy materials to lactic acid under light and aerobic conditions but it tends

to byproduct formation, such as acetic acid, ethanol and formic acid. Yeast is also

able to produce lactic acid. It has a high acid resistance even at pH as low as 1.5;

the fermentation might be conducted without neutralizing agent. Nevertheless,

almost all kinds of wild yeasts, with the potential to produce lactic acid, generate just

a small amount of lactic acid.14 Additionally, fungi can directly convert starchy

materials to lactic acid. Due to their amylolytic characteristics, lactic acid is produced

without any additional saccharification process, and the separation from the

fermentation broth is easy due to the filamentous structure of fungi. Fungi are well

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 suited for lignocellulosic fermentation as they are in general able to utilize pentose

and hexose.1 Although these microorganisms can convert starchy material and

lignocellulose, which are lower cost biomass than the high sugar material, or

avoiding the neutralizing agent cost, they lead to the opportunity of using more
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complex nutrients.

For the lactic acid isolation, several processes have been investigated for the

replacement of the conventional processes. To identify novel processes which may

find a role for the isolation and purification of lactic acid, a decision matrix; a method

employed in TIPS (Theory of Inventive Problem Solving) has been proceeded.

Decision matrix procedure for evaluation of lactic acid isolation processes is shown

in Figure 2. The assumption for the development of the decision matrix is a binary

mixture of water and lactic acid, based on substance properties, such as boiling

point, molecular weight, et cetera, rating of the unit operations has been done. The

methodology is applied to identify promising processes for the isolation of lactic acid

from fermentation broth on an objective basis. With respect to the cost of the unit

operation Mungma et al.43 developed a decision matrix in a chronological order.

Mechanical unit operations are less costly than mass transfer unit operations. In this

paper reactive separation technologies, which are the most expensive processes,

are addressed too. In case of reactive separation technologies, the assumption of a

binary mixture changes from water/lactic acid to lactic acid and the corresponding

ester.

According to the decision matrix, electrophoresis is the only mechanical unit

operation which may be used for the separation of the binary mixture of water/lactic

acid. It is assumed, that due to the difficult transfer into the industrial scale this topic

is not addressed at present. No literature on this topic was found. The decision

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 matrix for mass transfer unit operations recommends the processes permeation,

pervaporation, electro-dialysis and molecular sieving.

The relevant literature shows that one or several methods evaluated positive

in the decision matrix, are under development. But not all unit operations which are
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evaluated positive in the decision matrix are reported in literature. Membrane

technologies, such as microfiltration, ultrafiltration, nanofiltration, pervaporation, and

electro-dialysis are the most environmentally friendly methods currently available.

With these technologies high purity and high yield of lactic acid can be achieved.

Furthermore, membrane units are easily integrated in a conventional production

line.44

A short summary on membrane operation shows that they are promising

technologies used in lactic acid production. Ultrafiltration is usually used as a pre-

treatment process. It is useful to remove protein and cells from the fermentation

broth prior to the lactic acid purification step.45–47 It was also used for the clarification

of the fermentation broth.48 Nanofiltration has been investigated extensively for the

recovery of lactic acid from fermentation broth. The pH-value of the fermentation

broth strongly affects the lactic acid transport through the nanofiltration membrane.

Due to the addition of sodium hydroxide during the fermentation process osmotic

pressure increases, which leads to decreased permeate flux, an increase in the

rejection rate and hence a lower purification. Both, permeation and rejection increase

with pressure. The feed concentration could also influence the rejection and the

permeation of nanofiltration membranes. Solute rejection decreases with increasing

feed concentration owing to a decrease in electric repulsion force (Donan

exclusion).49 Moreover, an important parameter to estimate the influence of solute

size on its retention is the membrane pore size. Flat sheet cross flow nanofiltration

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 membranes with different pore size of 0.57 nm, 0.55 nm, and 0.54 nm were tested

for the separation of lactic acid. The nanofiltration membrane with a pore size of 0.55

nm could retain approximately 90% of sugar, and allow more than 70% of lactic acid

to permeate50 in single step operation.

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Electro-dialysis is one of the most promising membrane techniques for the

purification of lactic acid. There are two types of electro-dialysis technology applied,

two-stage electro-dialysis consisting of a desalting step and a water-splitting or

acidifying step, and electro-dialysis with double exchange reaction, which is a single

step process. Reports reveal that the two-stage electro-dialysis technology is an

efficient technique for the lactate recovery from the fermentation broth and the

conversion into lactic acid in terms of environmental aspects. It can enhance the

concentration of lactic acid more than two times in comparison with the initial lactate

concentration.48,51

Due to simple operation, low energy consumption, and high selectivity,

sorption techniques such as ion-exchange and adsorption have been arisen. Ion-

exchange chromatography has been developed to proceed in shorter time than

conventional downstream processing, including lactate ion adsorption, elution, and

lactate hydrolysis to lactic acid.52 Chromatography leads to high yield of lactic acid

and does generate minimum amount of waste. Several types of ion-exchangers have

been used for the recovery of lactic acid.52–54 Two-step separation techniques

comprising of Amberlite IRA 96 and Amberlite IR 120 were investigated in order to

reduce the steps and the cost of lactic acid purification.55 In the first step, lactic acid

was separated from anions in the broth by a weak anion exchange resin, after that a

strong cation exchange resin was used to separate lactic acid from cations in the

broth, which were trapped on the resin. Resulting lactic acid purity was 99%. With

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 the combination of the two ion exchange resins cost reduction in large-scale lactic

acid production is significant. However, other anions in the fermentation broth,

namely SO42- and Cl-, can interact with the lactic acid on the ion-exchanger.56

Silicalite molecular sieves possess a proper pore size for lactic acid. Regeneration of
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the silicalite molecular sieves was tested seven times, over this cycles they kept load

capacity. However, this adsorbent has a lower lactic acid adsorption capacity than

polymeric adsorbents.56

Lyophilysation widely appears as an optional method for preservation of

bacteria and yeasts.57 Due to the difference in the freezing point of 16.8 °C between

water and lactic acid, lyophilysation is a potential method for lactic acid recovery.

Reactive separation has been found to be a promising alternative for the

recovery of lactic acid from fermentation broth with high purity and high yield.

Reactive separation technologies combine chemical conversion and separation in a

single or integrated process unit. Due to the chemical conversion, the substance

properties of the target product are changed. For the setup of the decision matrix in

Table 1 butyl lactate is used as target substance in a binary mixture with water. The

reaction yield for the esterification reaction is assumed to be 100% and catalyst need

is negligible.

Table 1 summarizes reactive separation techniques, which may be applied for

the isolation and purification of lactic acid. Esterification reactions are typically

reversible and equilibrium-limited processes with ester and water as products.

Higher ester yields can be obtained by shifting the equilibrium to the product side,

using hybrid processes such as reactive distillation and membrane-assisted reactors.

Kumar et al.58 investigated the esterification, distillation and hydrolysis in a batch

reactive distillation experimentally. The experiments were accompanied by modeling

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 and simulation. Batch reactive distillation can completely recover the lactic acid from

its aqueous solution, but a great deal of water needs to be vaporized together with

methyl lactate for the recovery of lactic acid from dilute lactic acid solution.

Therefore, batch reactive distillation is not an appropriate process in terms of energy

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consumption in comparison with the conventional approach of reaction followed by

distillation. The esterification of lactic acid and methanol in a two-phase continuous

stirred tank reactor, followed by continuous multi-stage reactive distillation for

hydrolysis was performed experimentally accompanied by simulation.59 Conversion

of hydrolysis can be enhanced by the continuous removal of volatile components

such as methanol and water from the reaction zone, thus pure lactic acid is obtained

from the bottom of the reactive distillation column. The distillation column with five

stages, two of them being reactive, produce lactic acid with a concentration of 81 g

kg−1 and methyl lactate conversion of 99.95%. The minimum operation time of

conventional and inverted batch reactive distillation for hydrolysis of methyl lactate to

lactic acid was studied.60,61 For both, conventional and inverted columns, the

presence of the reactants (methanol and lactic acid) in the reaction zone to complete

the conversion respectively the hydrolysis to lactic acid, has to be considered. For

conventional columns, reflux ratio has an important effect on the removal of the light

product methanol from the top of column, whereas the reflux ratio plays a significant

role in the removing of lactic acid from the bottom of the column in case of inverted

column operation. In order to minimize the total capital and operating cost, the

purification of lactic acid from fermentation broth by reactive distillation using design

of experiments was evaluated.62 This purification process presents great ability to

obtain high yield of ethyl lactate (~100%) and to enhance lactic acid concentration

from the initial concentration by three times. It can be concluded that reactive

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 distillation is technically feasible and advantageous for lactic acid purification.

Moreover, autocatalytic countercurrent reactive distillation of lactic acid with

methanol using a packed column followed by hydrolysis of methyl lactate using three

continuously stirred tank reactor in series was studied. The experiments were carried
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out in pilot plant equipment, lactic acid acted as catalyst.63 This process lead to

99.81wt% purity of lactic acid on water-free basis with an optical purity of 99.9%. The

advantage of the autocatalytic operation is that the complete hydrolysis of methyl

lactate is achieved without using a catalyst, thus avoiding contamination of the lactic

acid. Autocatalytic countercurrent reactive distillation can be operated at higher

temperatures, improving the reaction kinetics and leading to shorter columns. It

indicates that this technology can make the process economically viable for

commercial use. Since distillation is a process which consumes a great deal of

energy, thermal energy minimization in a reactive distillation process for lactic acid

recovery by optimizing the reflux ratio was also developed.64 The reactive distillation

step was carried out with a multi-reflux ratio strategy instead of a conventional

single-reflux ratio strategy bringing about a minimization of production time.

Approximately 56% of thermal energy was saved.

Although methanol is widely used in esterification for lactic acid

purification60,63–66, there are some studies using other alcohols such as ethanol62 and

butanol.67,68 The alcohol used for the esterification influences physical properties and

hence the purification process design. With increasing chain length, the water

solubility of the alcohol decreases, leading to a lager miscibility gap. Su et al.69

investigated the esterification with C1 to C4 alcohols and made an economic

evaluation of the processes. Due to formation of alcohol/water azeotropes, when

ethanol or isopropyl alcohol was used, the processes with the reactants methanol

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 and butanol turned out to be more cost efficient. For short payback periods, the

butanol process is preferred, whereas for long payback periods, the methanol

process is preferred.

Coupling of esterification reaction and membrane separations, such as

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pervaporation and permeation, have obtained much attention because these

processes enhance the yield of lactate ester, the conversion of lactic acid was close

to 100%.39,70 Another advantage of these processes is the low energy consumption

and no limitation due to the relative volatility compared with distillation.71 The hybrid

reactive stripper-membrane (RSM) process for hydrolysis of lactate ester was

studied in order to overcome the equilibrium-limitation of the reaction. When the

RSM process was compared with reactive distillation for the production of lactic acid

in a purity of 88wt%, 29% of energy cost was saved and conversion was increased

by 5.6%.72 The influence of feed temperature and feed composition on the

permeation behavior of the binary (water/ethanol, water/ethyl lactate and water/lactic

acid) and quaternary (water/ethanol/ethyl lactate/lactic acid) mixtures during

esterification were investigated under the aspect of optimized ethyl lactate yield.71,73

The total permeation flux was increased with increasing water content in the feed

and operating temperature in all binary and quaternary mixtures. However,

permeation flux was almost constant when the lactic acid concentration was

changed between 9 wt% and 30 wt%.

Process intensification of lactic acid production by integration of membrane

separation and fermentation process allows the in-situ production and isolation of

lactic acid. Two stage and three stage membrane filtration integrated fermenters

were developed for continuous lactic acid production from sugarcane juice. For the

combination of microfiltration and nanofiltration in two stage membrane filtration, L-

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 lactic acid can be isolated with a purity of 98% and a maximum product yield of

96%.74 The two stage membrane process leads to permeate fluxes in a range of 63

to 76 l m-2 h-1, which are acceptable for industrial application. The three stage

membrane filtration process consisted of microfiltration as first stage for the cell
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separation and, two following nanofiltration membrane separation steps. The final

solution contained L-lactic acid with a purity of 95% and a product yield of 96.5%.75

In conclusion, the two stage and the three stage integrated membrane fermentation

processes were more effective to produce high quality L-lactic acid than single step

membrane separation. With the single stage membrane process membrane fouling

in the cell recycle step was observed. Sikder et al.76 evaluated the economics of a

membrane integrated continuous process for the production of 95% pure lactic acid

from sugarcane juice in pilot scale. The production cost for this systems was

calculated to be 3.15 US $/kg. The fermentation step contributes with 36% to the

total fixed capital cost, whereas the isolation and purification steps contributes with

about 2% to the total fixed capital cost. Yeast contributes with 87% most to the

operating cost; Raw material costs account with 6% to the operating costs. These

results stress the search for cheaper nitrogen sources and raw materials. To

overcome the carbon catabolite repression, sweet sorghum juice was used as

carbon source. Membrane integrated repeated batch fermentation was investigated

to improve the yield of lactic acid.77 With sixth batches, which can be taken as a long

term operation, a lactic acid yield of 0.954 g g-1 and a lactic acid concentration of

60.25 g L-1 was obtained. A productivity of 17.55 g L-1 h-1 was reported.

Reactive extraction is a promising technology for lactic acid purification. Main

topics for reactive extraction are the type of extractant and the diluent used.

Extractant choice is related to phase equilibrium, selectivity, solubility and volatility.

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 Via reactive extraction lactic acid can easily be separated from fermentation broth,

also providing pH-control during the fermentation process. The reuse of extractant is

possible.8,78,79 Alamine-336 in octanol as a diluent was used for the reactive

extraction of lactic acid from broth in comparison with methyl isobutyl ketone and
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decanole.78 Results suggest to prefer octanol as diluent in terms of equilibrium data

and kinetics. Furthermore, tri-n-octylamine in n-octanol was used for reactive

extraction of lactic acid under slug flow operation in capillary micro reactors in

comparison with a batch extraction80 step. Because of high interfacial area and low

mass transfer resistance the system reached equilibrium in the capillary micro

reactor faster than in the batch reactor. Uslu et al.81 investigated the reactive

extraction of lactic acid from the fermentation broth, carried out at room temperature

by using tertiary amine consisting of tri-propylamine dissolved in different alcohols as

diluents. Isoamyl alcohol lead to the highest extraction efficiency with about 80%.

Lux et al.82 found that Cyanex 923 diluted in ShellsolT is, in regards of distribution

coefficient and hydrodynamics, a proper extractant for lactic acid extraction from

aqueous solution.

Economic aspects

Although the reactive separation technologies have higher efficiency than the

mechanical and mass transfer separation techniques, the production cost of the

reactive separation processes should be studied in terms of an economic aspect to

identify the best process route for lactic acid production and isolation. Therefore, the

economical evaluation of separation processes used for commercial scale lactic acid

purification does need some attention. The increase in demand of PLA has a

significant impact on the lactic acid price. The commercial prices of food grade lactic

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 acid range between 1.38 $/kg for 50 wt% to 1.90 $/kg for 88 wt%, and cost for

technical grade lactic acid with 88 wt% range between 1.59-1.88 $/kg.10,69,76 The

lactic acid production cost is targeted to be less than 0.9 $/kg.10,83 The numerous

economic studies of lactic acid production have been reported as presented in Table
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2. The research focused on overall processes of the lactic acid production including

the fermentation and the products isolation; some studies merely considered the

recovery processes. The final products for these economical assessments were

lactic acid or lactic acid with lactate at several concentrations. The evaluated cost of

the lactic acid production from fermentation with the mass transfer unit operation and

the reactive separation processes is between 0.523 – 3.480 $/kg. The operating cost

of purification of 1 kg of lactic acid (88 wt%) simulated for the reactive distillation

excluding the fermentation cost and the mass transfer separation processes

(solid/liquid separation, ultrafiltration, electro-dialysis, and multi-effect evaporation)

are 0.56 $/kg and 0.22 $/kg as seen in Route 1 and 2 respectively. The operating

cost for the reactive distillation is rather low. Even when the fermentation costs are

not included in this evaluation (Route 2), the total production likely meet the targeted

lactic acid production cost. Additionally, the production costs of pure lactic acid

(Route 3-5), including the fermentation and the purification steps, were estimated for

three different process routes. Route three summarizes the conventional production

process for the lactic acid production, including the precipitation of calcium lactate,

and esterification and hydrolysis using reactive distillation. The conventional route

still has the lowest production cost as compared to the routes four and five. The

conventional process is efficient and simple, but it produces plenty of calcium

sulphate, which is a low price by product which often needs to be disposed of. Thus,

the continuous fermentation with reactive extraction, re-extraction, esterification with

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 reactive distillation and hydrolysis (route 4) should be a feasible process. Although

production cost is a little bit higher than the conventional precipitation based process,

it does not form a low-price by product.

Accepted Article
Conclusions

Lactic acid has the potential to play an essential role in the replacement of

fossil fuel based bulk chemicals, as it acts as monomer for the production of

polylactic acid. Increasing lactic acid demand leads to an increase in research

activities focusing not only on the optimization of the fermentation process but

especially on the development and optimization of downstream processing. In this

study, state of the art for lactic acid production and isolation has been reviewed.

Technical and economical limitations of lactic acid production as well as the future

importance of lactic acid as a key product of the biorefinery have been elaborated.

Furthermore, state of research in this field and economic evaluation of reactive

separation processes such as reactive distillation and reactive membrane separation

have been considered. Research in the fermentation process focus on the raw

material, the nutrients and the bacteria strains. Self-inhibition of lactic acid production

can be overcome. Low cost lignocellulosic materials can be converted to lactic acid

by fungi. The studies focusing on the isolation and the purification of lactic acid

mainly deal with reactive separation processes such as reactive extraction, reactive

distillation, and reactive membrane separation. The productivity and lactic acid purity

achieved by reactive separation processes as well as their eco-friendliness are

interesting issues. As discussed in this review, the reactive distillation and the

reactive extraction are the interesting processes in term of high purity of L-lactic acid

over 95%, and the costs. The membrane processes can recycle the microorganism

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 resulting in the reduction of raw material cost, and purity of 98%. However, the

replacement of the conventional lactic acid isolation process by reactive separation

processes is not state of the art and does still need research activities to meet the

targeted lactic acid production price. The complexity of reactive separation

Accepted Article
technologies still leads to higher production cost compared with conventional lactic

acid production processes. Moreover, the lyophilysation is one interesting alternative

for the lactic acid isolation from fermentation broth, owing to the different in freezing

point between lactic acid and water.

Acknowledgements

The authors gratefully thank Ernst Mach-Stipendien, Ernst Mach weltweit

TSOA scholarship from Austrian Agency for International Cooperation in Education

and Research (OeAD-GmbH), Center for International Cooperation & Mobility (ICM)

for the financial support of this work.

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 Table 1. Decision matrix for reactive separation technologies.

Properties of target substance Reactive Chromatography Reactive Membrane

(Butyl lactate) distillation reactors separations

Property Value

MW [g/mol] 146.18 - + -
Accepted Article
MP [°C] -28 - - -

BP [°C] 185 + - -

Acidity (pKa) 13 - - +
3
Density [g/cm ] 0.984 - - -

Solubility in water 58.70 - - -

Enthalpy [kJ/mol] 5 + - -

pH value 75.5 - - +

Flash point [°C] 0.4 - - -

Vapor pressure 288.76 + - -

[mm.Hg] at 25 °C
-6
Heat capacity 2 x 10 + - -

[J/kg.K)

Viscosity 146.18 - + -

[Pa.s] 88.6%sol

Henry constant -28 - - -

3
[atm-m /mol]

Freezing point [°C] 185 - - -

Total 4 2 2

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 Table 2. The assessment costs for lactic acid production.

Route Processes Raw Product concentration Production Ref

materials (% w/w) cost ($/kg)
69
1 Reactive distillation - 88 0.22
excluding fermentation cost
Accepted Article
(use methanol or butanol for
esterification)
83
2 Fermentation, solid/liquid Corn 88 0.56
separation, ultrafiltration, stover
electro-dialysis, and multi-
effect evaporation
84
3 Batch fermentation with - 100 1.40
addition of lime, precipitation
of calcium lactate, dissolution
in methanol, acidification to
separate calcium sulphate,
esterification
84
4 Continuous fermentation with - 100 1.59
reactive extraction, re-
extraction, esterification with
reactive distillation and
hydrolysis
84
5 Batch fermentation with - 100 1.74
addition of ammonium
hydroxide, micro filtration,
monopolar electrodialysis
85
6 Fermentation, electrodialysis Crude 85 0.55
membrane based starch
hydrolysate
76
7 Fermentation, membrane- Sugarcane 80 3.15
integrated bioreactor
86
8 Fermentation, centrifugation, Wheat flour 70 0.83
ultrafiltration, electrodialysis,
evaporation
87
9 Fermentation, ultrafiltration, Ultrafiltered 50 1.25
ion-exchange, reverse sweet
osmosis, vacuum cheese
evaporation whey

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Accepted Article

e 1. Lactic acid produ

Figure uction by microbial fermentation
n.

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Accepted Article

e 2. Decisio
Figure on matrix procedure for evaluattion of lactiic acid isolation processes.

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