Journal of Chemical Technology and Biotechnology J Chem Technol Biotechnol 81:1119–1129 (2006)

Review
Lactic acid: recent advances in products,
processes and technologies – a review
Rathin Datta∗ and Michael Henry
Energy Systems Division, Argonne National Laboratory, Argonne, IL 60439-4815, USA

Abstract: Lactic acid, the most widely occurring hydroxycarboxylic acid, is an enigmatic chemical. It was
discovered a long time ago and its use in food preservation and processing and as a specialty chemical has grown
over the years with current production of about 120 000 t yr−1 . Its potential as a major chemical feedstock, derived
from renewable carbohydrates by sustainable technologies, to make plastics, fibers, solvents and oxygenated
chemicals, had also been recognized. Recently, new technologies have emerged that can overcome major barriers
in separations and purification and processing. Advances in electrodialysis (ED) and bipolar membranes and one
particular process configuration termed the ‘double ED’ process, a specific combination of desalting ED followed
by ‘water-splitting’ ED with bipolar membranes, has given very promising results, showing a strong potential for an
efficient and economic process for recovery and purification of lactic acid without generating a salt waste. For the
production of polymers, several advances in catalysts and process improvements have occurred in the technology
to produce dilactide and its polymerization to produce plastics and fibers by Natureworks LLC, which is the leader
in lactic polymer technology and markets. Other advances in esterification technology with pervaporation and
development of biosolvent blends also have a high potential for ‘green’ solvents in many applications. Recently,
a considerable amount of pioneering effort in technology, product development and commercialization has been
expended by several companies. To overcome the barriers to replace long-established petroleum-derived products,
further real support from consumer, regulatory and government organizations is also needed.
 2006 Society of Chemical Industry

Keywords: lactic acid; oxychemicals purification; polymers; production; solvents

INTRODUCTION used a chemical technology. Thus lactic acid has been

Lactic acid (2-hydroxypropanoic acid), CH3 CHOH considered a relatively mature fine chemical in that
COOH [CAS 50-21-5], is the most widely occurring only its use in new applications, e.g. as a monomer
hydroxycarboxylic acid. It was first discovered in in plastics or as an intermediate in the synthesis of
1780 by the Swedish chemist Scheele. Lactic acid high-volume oxygenated chemicals, would cause a
is a naturally occurring organic acid that can be significant increase in its anticipated demand.2 By
produced by fermentation or chemical synthesis. It 2003, several major changes had occurred in the
is present in many foods both naturally or as a product USA. Sterling exited the lactic acid business and
of in situ microbial fermentation, as in sauerkraut, two new manufacturers, Archer Daniels Midland
yogurt, buttermilk, sourdough breads and many other (ADM) and Cargill Dow (a joint venture between Dow
fermented foods. Lactic acid is also a principal Chemical Company and Cargill Corporation), entered
metabolic intermediate in most living organisms, from
the business, both using carbohydrate fermentation
anaerobic prokaryotes to humans.
technology. In early 2005, Cargill bought out Dow
Although lactic acid is ubiquitous in nature and has
from this joint venture and established Natureworks
been produced as a fermentation by-product in many
LLC as a wholly owned subsidiary. ADM’s focus
industries (for example, corn steep liquor, a principal
by-product of the multi-million tons per year corn has been on lactic acid and its derivatives for
wet-milling industry, contains approximately 25 wt% conventional and other uses whereas Natureworks
lactic acid on a dry solids basis), it has not been a large- LLC has been the primary leader in the lactic-based
volume chemical. By 1990 its worldwide production polymer business. In the Far East, Musashino has been
volume had grown to approximately 40 000 t yr−1 with reportedly manufacturing lactic acid by carbohydrate
two significant producers, CCA Biochem in The fermentation technology with Chinese partners. The
Netherlands, with subsidiaries in Brazil and Spain, current worldwide production (including polymer
and Sterling Chemicals in Texas City, TX, USA, as uses) is estimated to be around 120 000 t yr−1 . Thus,
the primary manufacturers.1 CCA used carbohydrate in the last decade, lactic acid production has grown
feedstocks and fermentation technology and Sterling considerably, mainly owing to the development of new

∗
Correspondence to: Rathin Datta, Energy Systems Division, Argonne National Laboratory, Argonne, IL 60439-4815, USA
E-mail: rdatta@anl.gov
(Received 30 August 2005; revised version received 21 September 2005; accepted 21 September 2005)
Published online 2 May 2006; DOI: 10.1002/jctb.1486

 2006 Society of Chemical Industry. J Chem Technol Biotechnol 0268–2575/2006/$30.00

R Datta, M Henry

uses, and the production technology is now primarily Technical-grade lactic acid has long been in use
based on carbohydrate fermentation. in the leather tanning industry as an acidulant for
deliming hides and in vegetable tanning. In various
textile-finishing operations and acid dying of wool,
technical-grade lactic acid was used extensively.
PRODUCTS AND USES – TRADITIONAL Cheaper inorganic acids are now more commonly
Traditionally, the principal use of lactic acid is in used in these applications. The future availability of
food and food-related applications, which in the USA lower cost lactic acid and the increasing environmental
accounted for approximately 85% of the demand. The restrictions on waste salt disposal may reopen these
rest (∼15%) of the uses are for nonfood industrial markets for lactic acid.
applications. Currently, with the development and Traditionally, lactic acid is used in a wide variety of
commercialization of the biopolymers, lactic acid small-scale, specialized industrial applications where
use has increased considerably and 20–30% of the the functional speciality of the molecule is desirable.
2005 production is estimated to be in these new Examples include pH adjustment of hardening baths
applications. The current spot price, as posted in the for Cellophane used in food packaging, a terminating
Chemical Marketing Reporter, of heat-stable lactic acid agent for phenol-formaldehyde resins, alkyd resin
is about $0.70 lb−1 . In the future and as discussed later, modifier, solder flux, lithographic and textile printing
the growth of lactic acid is expected to come from the developers, adhesive formulations, electroplating and
development of new, large-volume uses, particularly electropolishing baths and detergent builders (with
as a feedstock for biodegradable polymers, ‘green’ maleic anhydride to form carboxymethoxysuccinic
solvents and oxygenated chemicals acid-type compounds). Owing to the high cost and low
As a food acidulant, lactic acid has a mild acidic volume of production, these applications accounted
taste, in contrast to other food acids. It is nonvolatile, for only 5–10% of the consumption of lactic acid.1
odorless and is classified GRAS for general-purpose Lactic acid and ethyl lactate [CAS 97-64-3] have
food additives by the FDA in the USA and by long been used in pharmaceutical and cosmetic appli-
other regulatory agencies elsewhere. It is a good cations and formulations, particularly in topical oint-
preservative and pickling agent for sauerkraut, olives ments, lotions, parenteral solutions and biodegradable
and pickled vegetables. It is used as an acidulant, polymers for medical applications such as surgical
flavoring, pH buffering agent or inhibitor of bacterial sutures, controlled-release drugs and prostheses. A
spoilage in a wide variety of processed foods such substantial part of pharmaceutical lactic acid is used as
as candy, breads and bakery products, soft drinks, the sodium salt [CAS 16595-31-6] for parenteral and
soups, sherbets, dairy products, beer, jams and jellies, dialysis applications. The calcium salt [CAS 5743-
mayonnaise, processed eggs and many other processed 48-6] is widely used for calcium deficiency therapy
foods, often in conjunction with other acidulants.3 An and as an effective anti-caries agent. As humectants in
emerging new use for lactic acid and its salts is in the cosmetic applications, the lactates are often superior
disinfection and packaging of carcasses, particularly as natural products and more effective than polyols.3
those of poultry and fish, where the addition of Ethyl lactate is the active ingredient in many anti-
aqueous solutions of lactic acid and its salts during acne preparations. The use of the chirality of lactic
processing increases shelf-life and reduces the growth acid for synthesis of drugs and agrochemicals is an
of anaerobic spoilage organisms such as Clostridium opportunity for new applications for optically active
botulinum.4,5 lactic acid or its esters. The chiral synthesis routes to
A large fraction (>50%) of the lactic acid for R-(+)-phenoxypropionic acid [CAS 1129-46-0] and
food-related uses goes to produce emulsifying agents its derivatives using S-(−)-lactate ester as a chiral
used in foods, particularly for bakery goods. The synthon have been described.3 These compounds are
emulsifying agents are esters of lactate salts with used in herbicide production. Another use, as an opti-
longer chain fatty acids. Four important products cally active liquid crystal using lactic acid as a chiral
are calcium and sodium stearoyl-2-lactylate [CAS synthon, has been described.6 These advances open
25 383-99-7], glyceryl lactostearate [CAS 1338-10- up new small-volume specialty chemical opportunities
9] and glyceryl lactopalmitate [CAS 1335-49-5]. Of for optically active lactic acid and its derivatives.
the stearoyl lactylates, the calcium salt [CAS 5793-94-
2] is a good dough conditioner and the sodium salt is
both a conditioner and an emulsifier for yeast-leavened PRODUCTS AND USES – RECENT
bakery products. The glycerates and palmitates are DEVELOPMENTS
used in prepared cake mixes and other bakery products Its two functional groups permit a wide variety of
and in liquid shortenings. In prepared cake mixes, the chemical reactions for lactic acid. The primary classes
palmitate improves cake texture, whereas the stearate of these reactions are condensation, esterification,
increases cake volume and permits mixing tolerances.3 reduction and substitution at the alcohol group.7
The manufacture of these emulsifiers requires heat- Using such reactions, lactic acid can be used for
stable lactic acid; hence only the heat-stable food products that potentially have very large-volume uses
grade is used for this application. in industrial applications and consumer products.

1120 J Chem Technol Biotechnol 81:1119–1129 (2006)

DOI: 10.1002/jctb
 Lactic acid

Catalytic Polymerization Plastics

Dilactide
Distillation Fibers

Bio-based
Alcohol
Solvents

Ethyl Lactate Blending Biosolvent

Esterification
(Lactate Esters) Blends

Fermentation &
Carbohydrates Lactic Acid
Purification

Hydrogenolysis Propylene
Glycol

Dehydration Propylene
Oxide

Catalytic Acrylic Acid

Dehydration Acrylate Ester

Figure 1. Lactic acid-based potential products and uses.

The primary classes of such products are polymers are biodegradable thermoplastics. The L-isomer of
for plastics and fibers, solvents for formulations and lactic acid is the preferred feedstock for dilactide
cleaning and oxygenated industrial chemicals. Thus production because it provides a high dilactide
lactic acid is one of the primary platform chemicals yield and a high molecular weight polymer with
that can be derived from renewable carbohydrates and a high degree of crystallinity and tensile strength.
used to make a wide variety of useful products. This Furthermore, a fairly wide range of properties
is shown schematically in Fig. 1. can be obtained by copolymerization with other
oxygenated functional monomers such as glycolide,
Polymers caprolactone, polyether polyols and the D-isomer of
Because lactic acid has both hydroxyl and carboxyl lactic acid. The actual compositions of the polymers
functional groups, it undergoes intramolecular or self- are proprietary to the various manufacturers. The
esterification and forms linear polyesters, lactoyllactic polymers are transparent, which is important for
acid and higher poly(lactic acid)s or the cyclic packaging applications. They offer good shelf-life
dimer 3,6-dimethyl-p-dioxane-2,5-dione [CAS 95- because they degrade slowly by hydrolysis, which
96-5] (dilactide). Whereas the linear polyesters, can be controlled by adjusting the composition
lactoyllactic acid and poly(lactic acid)s are produced and molecular weight. The properties of lactic
under typical condensation conditions such as by copolymers, which approach those of large-volume
removal of water in the presence of acidic catalysts, the petroleum-derived polymers such as polystyrene,
formation of dilactide with high yield and selectivity flexible poly(vinyl chloride) (PVC) and vinylidene
requires the use of special catalysts which are primarily chloride, have been summarized.2 There are numerous
weakly basic. The use of tin and zinc oxides and patents and articles on lactic acid polymers and
organostannates and -titanates for this purpose has copolymers, their properties, potential uses and
been reported.7 – 10 processes, including some that date back to the early
work by Carothers at Du Pont and other DuPont
2 CH3CHOHCOOH C6H8O4 + 2 H2O researchers.2,11 – 14
O Currently, Natureworks LLC (www.natureworks-
O O
OH O
llc.com) is the primary developer and commercializer
2 + 2
H H of lactic acid-based polymers and products, and
OH O O a recent patent search showed that over 100
Lactic acid Dilactide Water US patents in this area were assigned to this
company. The company produces and sells two
(1) types of products – the polydilactide-based resins
(Natureworks PLA ), used for plastics/packaging
Dilactide, also commonly termed lactide, is the applications, and the Ingeo polydilactide-based
primary feedstock for polymerization to make high fibers, that are used in specialty textiles and fiber
molecular weight polymers of lactic acid (PLA), which applications. Over the past 10 years, this company

J Chem Technol Biotechnol 81:1119–1129 (2006) 1121

DOI: 10.1002/jctb
R Datta, M Henry

has done extensive product development work, the precision cleaning. More recently, Vertec Biosolvents
magnitude of which becomes apparent from their Inc. (www.vertecbiosolvents.com) has been develop-
technical and applications literature. They have also ing and commercializing blends of these esters with
built a plant in Blair, Nebraska, with a nameplate other biologically derived solvents such as fatty acid
capacity of 300 million lb yr−1 for the production of methyl esters or D-limonene that can have a wide range
lactic acid and PLA. For product commercialization of solvating and cleaning properties.15,16 The US Envi-
they have partnered with many potential end-users ronmental Protection Agency (EPA) recently classified
and polymer processing equipment manufacturers. the lactate esters ethyl and butyl lactate as Class 4A
For plastics and packaging applications, both inert ingredient for use in the formulation of pesticides
general and detailed information on the properties and other bioactive compounds. The Class 4A desig-
of various grades of resins are available from the nation is given to compounds that have demonstrated
manufacturer. A variety of products such as cups, negligible toxicity and an excellent environmental pro-
cutlery, plates and saucers and food dispensing file. Thus, a good range of specialty applications and
containers can be made by injection molding. General commercial uses could be developed with these non-
and detailed guides for injection molding process using toxic, environmentally friendly lactate ester solvents
conventional injection molding equipment with PLA with other biologically derived solvents.17
resins are also available from the manufacturer. Some
of the advantages listed include superior clarity, good Oxygenated chemicals
heat deflection, readily degradable in the enviornment Large-volume oxygenated chemicals such as propylene
(compostable) and sustainability (renewable resource glycol (1.5 billion lb US production in 2004),
based). The US FDA and European regulatory propylene oxide (4 billion lb US production in 2004),
authorities have approved the resins for all food-type acrylic acid and acrylate esters (1.8 billion lb US
applications. production in 2004) and other chemical intermediates
Similarly, for fiber and fabric applications compar- such as lactate ester plasticizers can potentially be
ative properties of the PLA-based Ingeo with nylon, made from lactic acid.1,2,18 The advances made in
PET, rayon, cotton, silk and wool are available from hydrogenolysis technology can be further developed
the company. and integrated to make propylene glycol from lactic
Some of the advantages listed include: acid in the future.19 – 22
• lower specific gravity than other natural fibers – CH3CHOHCOOH + 2 H2 CH3CHOHCH2OH + 2 H2O
lighter products; O
• higher tenacity than natural fibers – tensile strength; OH
+2 H O
H OH + 2 H
• significantly lower moisture regain than natural HO
H
fibers – easier drying after wet; OH
• outstanding UV resistance compared with all fibers; Lactic acid Hydrogen Propylene glycol Water
• low refractive index, which produces intense colors (2)
on dyeing;
• compared with PET and other synthetics, lower Advances in catalysis and process technologies are
heat of combustion, less smoke when burned, high needed for efficient conversion of lactate to acrylate
water wicking and faster moisture spread. or propylene glycol to propylene oxide, even though
some of the early patents show the technical feasibility
Some of the negatives include:
of such conversions.23 – 26
• poor alkali resistance, causing strength loss in the CH3CHOHCH2OH CH3CHOCH2 + H2O
conventional dispersed dye process;
• low ironing temperature due to low crystalline melt OH + O
O H H
temperature. HO
Propylene glycol Propylene oxide Water
Thus, over the past 10 years, an extensive amount of
work has been done on developing and commercializ- (3)
ing PLA and its products. A more detailed analysis of CH3CHOHCOOH CH2CHCOOH + H2O
polymer technology undertaking is beyond the scope O
of this paper. OH
O
O
+
H H
Solvents OH
OH
Environmentally friendly, ‘green’ solvents are another Lactic acid Acrylic acid Water
potential growth area for lactic acid derivatives, partic-
ularly lactate esters of low molecular weight alcohols (4)
such as ethyl, propyl and butyl lactate. Purac Inc.
has developed and commercialized several special- In Table 1, these potential products and applica-
ized applications of lactate esters in electronics and tions and estimates of their overall size in terms of both

1122 J Chem Technol Biotechnol 81:1119–1129 (2006)

DOI: 10.1002/jctb
 Lactic acid

Table 1. Lactic acid: potential products, markets, volumes and value

US market World market Selling

volume volumea price ($ lb−1 ) Valuef
Products Uses (billion lb yr−1 ) (million t yr−1 ) [$ t−1 ] ($million yr−1 )

Polymers: plastics Degradable packaging, films 1.5 1.5 1.0c [2200] 3300
Polymers: fibers Specialty textiles, bedding, etc. 0.5 0.5 2c [4400] 2200
‘Green’ solvents (biosolvent Specialty formulations, industrial/ 0.5b 0.5 1b [2200] 1100
blends) machinery cleaning, etc.
Oxychemicals: propylene glycol Humectants, food processing, 1.5 1.5 1d [2200] 3300
deicers, polymers
Oxychemicals: propylene oxide Polyurethanes, plastics, etc. 4.0e 4.0 0.9d [2000] 8000
Oxychemicals: acrylates Polymers, plastic films, coatings 1.8 1.8 1d [2200] 4000
Total 9.8 9.8 21 900
a
World market volume is usually about 2–2.5-fold of the US market volume; we have rounded it off to 2.2-fold and reported as metric tons (t).
b
Market size potential and selling price targets are based on Industrial Bioprocessing, (IB market forecast), Vol. 23, No. 4 (2004), and also authors’
estimates from various reports.
c Selling prices for the lactic polymers and fibers are targets, based on author’s estimates from various publications.
d Selling prices (US) for the oxychemicals are from the Chemical Marketing Reporter, September 2005.
e This excludes the volume of propylene oxide that is used to make propylene glycol.
f The total potential value is the total scope worldwide at current estimates of market volumes and prices.

mass/volume and product sales value are summarized. Traditional technologies

For the oxygenated chemicals which are known com- Lactic acid can be manufactured either by chemical
modities, the product volumes and prices have been synthesis or by carbohydrate fermentation; both have
taken from commercial journals such as the Chemi- been used for commercial production in the past. In
cal Marketing Reporter and other sources such as the the USA, lactic acid was manufactured synthetically by
Stanford Research Institute (SRI) Chemical Economic Sterling Chemicals using the lactonitrile route, which
Handbook (CEH) reports. For the polymers and sol- was a byproduct of acrylonitrile technology. Sterling
vents we have derived our estimates from many recent exited the business in the early 1990s. In the Far East,
news reports, topical reports and announcements. Musashino Chemical used this technology for some of
In summary, lactic acid has a very large potential to its production but recently converted to fermentative
be a major ‘platform’ chemical that can be used for production. The synthetic route had many major
polymers – plastics and fibers; solvents – formulations limitations that included limited capacity because of
and cleaning and three-carbon oxygenated chem- the tie to a byproduct of another process, inability to
icals that are used in large quantities for many make the desirable L-lactic acid stereoisomer only and
applications. Recently, considerable pioneering effort high manufacturing costs.
in product development and commercialization has Currently, all lactic acid manufacture is based on
been invested by a few companies and considerably carbohydrate fermentation and the major manufactur-
more is needed. Real support from consumer, regu- ers are CCA Biochemical BV of The Netherlands with
latory and government organizations is also needed plants in Europe, Brazil and USA, Archer Daniels
to overcome the inertia and barriers to change to Midland (ADM) in the USA, Musashino in the Far
sustainable products from renewable resources. Fur- East and Natureworks LLC, which has been the pri-
thermore, the lactic acid production technologies also mary leader in the lactic-based polymer business.
need to be further advanced and implemented to The existing commercial production processes use
become technically and economically feasible and homolactic organisms such as Lactobacillus delbrueckii,
environmentally sound. This is discussed further L. amylophilus, L. bulgaricus and L. leichmanii. Mutant
below. fungal strains of Aspergillus niger are also reportedly
used. A wide variety of carbohydrate sources, e.g.
molasses, corn syrup, whey, dextrose and cane or beet
MANUFACTURING TECHNOLOGIES sugar, can be used. The use of a specific carbohydrate
We will focus on the manufacturing technologies for feedstock depends on the price, availability and its
the production of purified lactic acid and key interme- purity. Proteinaceous and other complex nutrients
diates such as esters and other derivatives. Discussions required by the organisms are provided by corn
and analysis of the advances in polymerization tech- steep liquor, yeast extract, soy hydrolysate, etc.
nologies with the PLA resins are beyond the scope Excess calcium hydroxide/carbonate is added to the
of this review. First, the traditional technologies for fermenters to neutralize the acid, maintaining the pH
lactic acid production and their limitations are briefly around 5–6, and produce a calcium salt of the acid in
discussed. Following that, some promising emerging the broth. The fermentation is conducted in a batch
technologies, particularly in the fields of separations or fed-batch mode, taking 2–4 days to complete, and
and purification, are discussed. lactate yields of approximately 90 wt% from a dextrose

J Chem Technol Biotechnol 81:1119–1129 (2006) 1123

DOI: 10.1002/jctb
R Datta, M Henry

equivalent of carbohydrate are obtained. It is usually Carbohydrate

desired to keep the calcium lactate in solution so
that it can be easily handled with the cell biomass Nutrients Sterilization
and other insolubles and the final concentration
achieved is around 10 wt%. The calcium lactate- Anaerobic
Neutralization
containing broth is filtered to remove cells, carbon Agent (Lime) Fermentation
treated, evaporated and acidified with sulfuric acid to
convert the salt into lactic acid and insoluble calcium Sulfuric Acid Acidulation
sulfate, which is removed by filtration. The filtrate
can be further purified using carbon columns and ion Rotary Drum
exchange and evaporated to produce technical- grade Filter Aid Filter Press
Filtration
lactic acid, but not a high-purity, heat-stable product, "Waste
Gypsum"
which is required for the stearoyl lactylates, polymers, Evaporation
solvents and other value-added applications. For the
high-purity product, the technical-grade lactic acid
Esterification
is esterified with methanol or ethanol and the ester Ethanol Waste Purge
Reactor/Column
is recovered by distillation, hydrolyzed with water,

Dehydrating
Mol. Sieve
evaporated and the alcohol recycled. This separation Ethanol Column
process produces a highly pure product which is water-
white and heat stable.
Lights Column Lights Purge

C6 H12 O6 −−−→ 2 CH3 CHOHCOOH

(5a) Ester Column Heavy Impurities Purge

2 CH3 CHOHCOOH Ca(CH3 CHOHCOO)2 Water

−−−→ Ethanol Recycle
+Ca(OH)2 +2 H2 O IX Hydrolysis

(5b)
Ca(CH3 CHOHCOO)2 2 CH3 CHOHCOOH Purified Lactic Acid
−−−→
+H2 SO4 +CaSO4 Figure 2. Conventional process for lactic acid manufacture from
(5c) carbohydrate.

Some of the economic hurdles and process cost

centers of this conventional carbohydrate fermentation bioenergetics. Electrons or reducing equivalents are
process, shown schematically in Fig. 2, are in the conserved in anaerobic bioconversions and the achiev-
complex separation steps which are needed to recover able yields are therefore near theoretical values. For
and purify the product from the crude fermentation example, the theoretical yield of lactate from dex-
broths. Furthermore, approximately 1 t of crude trose is 100% (w/w) or 2 mol per mole. However, the
gypsum, CaSO4 , is produced and as a waste byproduct metabolic energy obtained is fairly low, enough for
needs to be disposed of for every ton of lactic cell growth and also non-growth associated product
acid produced by the conventional fermentation formation, but not enough for maintaining a proton
and recovery process.27,28 These factors have made gradient between the cell and its external environment.
large-scale production by this conventional route This leads to free diffusion of the protonated acid into
economically and ecologically unattractive. the cell and cessation of metabolic activity. This was
conclusively established by several laboratories in the
Emerging technologies mid-1980s, including the present author’s (R.D.) lab-
The primary technology barriers to cost-effective pro- oratory at Corn Products Corporation. and results of
duction of lactic acid are in separations and purifi- the metabolic studies were published.29 One way to
cation. One major barrier is the ‘cation elimination’ increase the metabolic energy obtained would be to
or the ‘salt’ problem. The fermentation operates most conduct the bioconversion under oxidative conditions,
efficiently and effectively at near neutral pH, which but then the electrons would not be conserved and
requires neutralization and produces the salt of the acid yields would be significantly lower. This conundrum,
instead of the acid itself. This is true for many other based on fundamental bioenergetics, was recognized
anaerobic acidogenic fermentations such as acetate, by several research teams and organizations, which
succinate, propionate, butyrate and others, which have focused their efforts on initiating and developing novel
high yields but low metabolic activity when the pH is and advanced separation technologies that might over-
low. Even for fungal fermentations for lactic acid, come this ‘salt’ problem.
pH tolerance is not good and salts are predominantly Recent results of genetic engineering work with
produced. yeasts to make lactic acid producers or genome
This pH intolerance barrier for anaerobic acido- shuffling of Lactobacillus for increasing acid tolerance
genic bioconversions is fundamental and is due to have been published30,31 and these do not show

1124 J Chem Technol Biotechnol 81:1119–1129 (2006)

DOI: 10.1002/jctb
 Lactic acid

any significant advance in overcoming this problem. One particular process configuration, termed the
In the work published by the large team led ‘double ED’ process, (Fig. 4), has been developed and
by Porro,30 Kluyveromyces lactis yeast strain was piloted at Michigan Biotechnology Institute (MBI)
genetically engineered to become a homolactate and at Argonne National Laboratory (ANL) and has
producer. In actual fermentation tests at a low final given very promising results.35,36 This process uses a
pH of 2.8–3.0, the organism was able to produce only desalting ED unit to remove the multivalent cations
about 30 g L−1 of protonated lactic acid with yields of and concentrate the lactate salt, followed by a ‘water-
about 0.7–0.9 mol per mole of dextrose, which is only splitting’ ED unit with bipolar membranes to produce
35–45% of theoretical, uneconomic for a commercial concentrated lactic acid and alkali for recycle.
process. The desalting ED (shown schematically in Fig. 5)
Hence technologies that would allow the conversion is a critical step that enables the process to operate
of the salt to the corresponding acid and alkali efficiently and economically. This step:
without consuming another acid or large amount of
energy have been critical. The other problems are • Concentrates the lactate salt by 2-fold or higher,
in purification, where the efficient production of a from a feed broth concentration of 8–10 to about
key intermediate such as an ester with high yield and 20 wt%.
purity is very important. Recent advances are discussed • Purifies the product (10–20 fold purification on
below. proteins, peptides, sugars and other non-ionic
impurities).
Advanced electrodialysis technologies • Rejects divalent ions by 98–99% (using monovalent
Advances in membrane-based separation and purifi- cation selective membranes).
cation technologies, particularly in microfiltration,
ultrafiltration and electrodialysis (ED), have led to the Dextrose
Ammonia
inception of new processes for lactic acid production Makeup
that do not produce a salt waste. Successful com-
Fermentation
mercial development of bipolar ED membranes has
recently occurred.32 – 34 These membranes can split Ammonium
and separate water to protons (H+ ) and hydroxyl Lactate Broth
(OH− ) ions as shown schematically in Fig. 3 and the
membranes can operate at about 80% of the theoret- Microporous
Filtration
ical thermodynamic efficiency.33,34 This technology
advance now enables the H+ to transport to the acid
anion to form the free acid and the OH− ion to trans- Desalting
port to the cation compartment to form the free base. Electrodialysis
Despite the recent advances in bipolar membranes,
they have the fundamental problem of intolerance
to multivalent cations such as calcium and magne- Chelation
sium that form insoluble hydroxides at the critical
interface of the bipolar membrane where the ions sep-
arate. Typically, the tolerance limit for these divalent Water-Splitting
Electrodialysis
cations is about 1 ppm. Fermentation broths contain
Ammonia
much higher concentrations, often in the region of
Recycle
1000 ppm. Hence a successful process with bipolar Polishing
membranes requires critical integration of key process Ion Exchange
steps that would work efficiently and economically. Lactic Acid

Evaporation
A I C
Ethanol Makeup

Esterification

H2O
+ -
Distillation/Hydrolysis

Ethanol,
H+ H+
+ Recycle
OH- OH- A - Anion permselective layer
C - Cation permselective layer Purified Lactic Acid
I - Interface layer

Figure 3. Bipolar electrodialysis membrane schematic and operation. Figure 4. Double-ED process schematic.

J Chem Technol Biotechnol 81:1119–1129 (2006) 1125

DOI: 10.1002/jctb
R Datta, M Henry

Concentrated Product
(Ammonium Lactate)
Desalted Broth
(Recycle)

C A C A C A C

O O O
M++ M++ M++

CATHODE
M+ M+ M+
ANODE

+ -
X-- X--
X- X- X-

M+X- M+X- M+X-

O O O
M++ M++ M++
Anolyte Catholyte

A - Anion exchange membrane

C - Cation exchange membrane
M+X- - Lactate salt (M+ = NH4+, X- = CH3CHOHCOO-)
Feed Broth (Ammonium Lactate)
M++ - Divalent/Multivalent Cations
O - Non-ionized or weakly ionized components

Figure 5. Desalting ED operation schematic.

Alkali
(Ammonium Hydroxide)
Lactic
Acid

C B C B C B C

H+X-
CATHODE

OH- OH- OH-

ANODE

+ -
M+ M+ M+
H+ H+ H+
X- X- X-

M+X- M+X- M+X-

Anolyte Catholyte

C - Cation exchange membrane

B - Bipolar membrane
M+X- - Lactate salt (M+ = NH4+, X- = CH3CHOHCOO-)
H+ - Hydrogen ions
Concentrated Product Feed -
OH - Hydroxide ions
(Ammonium Lactate)

Figure 6. Water-splitting ED operation schematic.

• Has a high recovery yield (>95% yield of lactate to stream to the range of 5–10 ppm and reduces the
the product from the feed). need for chelation by >95%.
• Moreover, the power consumption to do all of this The water-splitting ED step using the two-
is low, approximately 0.33 kWh kg−1 (0.15 kWh compartment ‘cation-bilpolar’ configuration (shown
lb−1 ) of lactate and allows a high current density to schematically in Fig. 6) also permits efficient and
be maintained. economic operation. This step can achieve:

• Low power consumption [0.55 kWh kg−1 (0.25

All of these benefits make the overall process kWh lb−1 ) of lactic acid].
efficiency and economics attractive. The increase in • High current density (1000 A m−2 ).
concentration decreases the subsequent evaporation • High (99%) acidification of the lactate salt.
energy load by half, the purification decreases the • Reduced fouling and long membrane life because
costs of downstream purification steps, the divalent ion organic foulants are exposed to the cation mem-
removal is particularly important because it reduces branes only, which have much lower fouling ten-
the Ca2+ and M2+ concentrations in the product dency than anion membranes.

1126 J Chem Technol Biotechnol 81:1119–1129 (2006)

DOI: 10.1002/jctb
 Lactic acid

• The alkali stream containing the aqueous ammonia Purification technologies

can be readily stripped and the concentrated Efficient purification technologies that give high yield
aqueous ammonia recycled. and purity for the key intermediates such as dilactide
and lactate esters are also very important and two
The feasibility of the ‘double ED’ process has
recent advances are highlighted.
been shown at the pilot scale using a slip stream
For the production of polymers or other derivatives,
of lactate broth from an industrial fermentation
the technology to produce dilactide (the internal
process. The process has been shown to provide the
diester) is critically important. Several advances in
performance parameters that have been summarized
catalysis and process improvements have occurred and
above. Moreover, successful resolution of some critical
proprietary technologies have been developed. In the
long-term stability issues has also been demonstrated.
many patents issued to Cargill Inc., the development of
The desalting ED process has been operated for
continuous processes for the manufacture of dilactide
over 700 h with recycle. Over 350 clean-in-place
polymers with controlled optical purity from purified
(CIP) cycles have been conducted with no significant
lactic acid is described.10 The processes uses a
decrease in membrane integrity or performance. The
configuration of multistage evaporation followed by
water-splitting ED unit has been operated on the
polymerization to a low molecular weight prepolymer,
desalting ED product for over 1000 h with recycle
which is then catalytically converted to dilactide with
producing a steady stream of the lactic acid and alkali.
the purified dilactide being recovered in a distillation
During these operations, a great deal of performance
system by partial condensation and recycling. The
data and analysis of the membrane materials were
dilactide can be used to make high molecular weight
collected and showed no evidence of membrane
polymers and copolymers. The process has been
deterioration or loss of function. Hence the advances
able to use fermentation-derived lactic acid and
in electrodialysis technology and using the particular
the claimed ability to recycle and reuse the acid
configuration of the ‘double ED’ process described
and prepolymers could make such a process very
here have a strong potential to provide an efficient
efficient and economic.10 In a patent issued to Du
and economic process for recovery and purification
Pont,35 a process to make cyclic esters, dilactide and
of fermentation-derived lactic acid without generating
glycolide from their corresponding acid or prepolymer
salt waste.
is described. This process uses an inert gas such
Other technologies for recovery and salt as nitrogen to sweep away the cyclic esters from
elimination (non-ED) the reaction mass and then recovers and purifies
Other schemes without using electrodialysis have also the volatilized cyclic ester by scrubbing with an
been attempted. appropriate organic liquid and separates the cyclic
Ecochem Inc., a Du Pont–Conagra partnership, ester from the liquid by precipitation or crystallization
had developed a recovery and purification process and filtration of the solids. High-purity dilactide with
that produced a by-product ammonium salt instead of minimal losses, due to racemization, has been claimed
insoluble gypsum cake and the company intended to as an advantage for this process. Recycling and reuse
sell this as a low-cost fertilizer. A demonstration-scale of the lactic moiety in the various process streams have
plant based on whey feedstock had been completed to been claimed to be feasible.38 Currently, Natureworks
prove the process but the process was not successful LLC is the leader in the lactic polymer technology and
owing to several major separation problems and the markets and the development and implementation
enterprise was abandoned. of their dilactide technology has contributed to their
Cargill Dow, the primary developer of lactic poly- success.
mer technology and products, had been developing an In a recent patent, a process based on pervaporation-
alternative process based on tertiary amine/carbonate assisted esterification of ammonium lactate to ethyl
technology.37 In this process, sodium lactate is pro- lactate is described. This process is being further
duced by fermentation and the broth is concentrated developed with membranes that selectively permeate
and extracted with a tertiary amine solvent mixture water vapor and ammonia over ethanol and the ester
under CO2 pressure to produce and precipitate a and thus provide good selectivity and yield.39 The
sodium bicarbonate salt and an amine lactic acid aqueous ammonia can be recycled to the fermenter for
extract. This is back-extracted with hot water at 140 ◦ C neutralization of the acid produced and the ester can
and 100 psig to produce a lactic acid solution and a be further purified by distillation. If successful, this
regenerated amine solvent mixture that is recycled. technology could lead to an efficient and economic
The lactic acid can be further purified and converted process to make purified lactate esters such as ethyl
to the dilactide for polymer manufacture. The sodium lactate that are useful as solvents or in solvent blends
bicarbonate is further heated to produce sodium car- and can also be used to make purified lactic acid.
bonate and CO2 , which are recycled into the process.
Several years ago, Cargill Dow built a manufacturing Technologies for other derivatives and chemicals
plant for lactic polymers with a carbohydrate front end, Hydrogenolysis reaction technology designed to
but how much of this alternative lactic acid production produce alcohols from organic acids or esters
technology is being used has not been divulged. has also advanced recently; new catalysts and

J Chem Technol Biotechnol 81:1119–1129 (2006) 1127

DOI: 10.1002/jctb
R Datta, M Henry

processes give high selectivity and rates and operate success. Other advances in esterification technology
at moderate pressures.21,22 This technology has with pervaporation and development of biosolvent
been commercialized to produce 1,4-butanediol, blends also have a high potential for use as ‘green’
tetrahydrofuran and other four-carbon chemical solvents in many applications.
intermediates from maleic anhydride. In the future, Hence, from a technology viewpoint, major
such technologies could be integrated with low-cost advances and integration of bioprocessing, biochem-
lactic acid production processes to make propylene ical engineering, advanced membrane-based separa-
glycol and other intermediate chemicals.21,22 tions technologies, chemical catalysis and polymer
Further advances in catalytic dehydration and pro- processing have developed to bring out the poten-
cess technologies are needed for efficient conversion tial of lactic acid. Recently, a considerable amount
of lactate to acrylate or propylene glycol to propylene of pioneering effort in technology, product develop-
oxide, even though some of the early patents show the ment and commercialization has been expended by
technical feasibility of such conversions.23 – 26 several companies and considerably more is needed.
Furthermore, real support from consumer, regula-
tory and government organizations is also needed
CONCLUSIONS to overcome the inertia and barriers to change that
Lactic acid is an enigmatic chemical. It was discovered are so inherent in bringing out sustainable products
a long time ago and has been produced as a specialty from renewable resources to replace long-established
chemical for decades. Its use in food preservation and petroleum-derived products.
processing has grown over the years. Its potential as
a major chemical feedstock, derived from renewable
carbohydrates by sustainable technologies, to make REFERENCES
plastics, fibers, solvents, oxygenated chemicals, etc., 1 Datta R, Hydroxy carboxylic acids, in Kirk-Othmer Encyclopedia
had also been recognized.1,2,18 of Chemical Technology, 5th edn, Vol. 14, ed. by Seidel A.
Only recently, however, have new technologies Wiley, Hoboken, NJ, pp. 114–134 (2005).
emerged that can overcome major barriers in sep- 2 Lipinsky ES and Sinclair RG, Is lactic acid a commodity
chemical?, Chem Eng Prog 82:26–32 (1986).
arations and purification and processing. Advances 3 Lactic Acid and Lactates. Product Bulletin, Purac Inc., Arlington
in membrane-based separation and purification tech- Heights, IL (1989).
nologies, particularly in micro- and ultrafiltration and 4 Anders RJ, Cerveny JG and Milkowski AL, Method for delaying
electrodialysis and bipolar membranes (ED), have led Clostridium botulinum growth in fish and poultry. US Patent
to the inception of new processes for lactic acid pro- 4 888 191 (1989).
5 Anders RJ, Cerveny JG and Milkowski AL, Packaged foodstuff
duction. One particular process configuration, termed containing a lactate salt. US Patent 5017391 (1991).
the ‘double ED’ process, which is a specific combi- 6 Yoshinaga K, Katagiri K and Shinjo K, Lactic acid derivative,
nation of desalting ED followed by ‘water-splitting’ liquid crystal composition containing same and liquid crystal
ED with bipolar membranes, has given very promising device. US Patent 4812259 (1989).
results and has a strong potential to provide an efficient 7 Holten CH, Muller A and Rehbinder D, Lactic Acid: Prop-
erties and Chemistry of Lactic Acid and Derivatives. Interna-
and economic process for the recovery and purification tional Research Association, Verlag Chemie, Copenhagen
of fermentation-derived lactic acid without generating (1971).
salt waste. For the production of polymers or other 8 EI du Pont de Nemours & Co. Inc., Preparation of optically
derivatives, the technology to produce the dilactide active lactides. UK Patent 1007347 (1965).
internal diester is critically important. Several advances 9 De Vries KS, Preparation of polylactic acid and copolymers of
lactic acids. US Patent 4797468 (1989).
in catalysts and process improvements have occurred
10 Gruber PR, Hall ES, Kolstad JJ, Iwen ML, Benson RD and
and, in the many patents issued to Cargill Inc., the Borchardt RL, Continuous process for manufacture of lactide
development of continuous processes for the manu- polymers with controlled optical purity. US Patent 5142023
facture of dilactide polymers with controlled optical (1992). (see also related US patents 5359026; 5357035;
purity from purified lactic acid is described. The pro- 5338822; 5274073; 5264449; 5258488; 5247059; 5257058).
11 Murdoch JR and Loomis GL, Polylactide compositions. US
cesses use a configuration of multistage evaporation
Patent 4766182 (1987). (see also US Patent 4800219).
followed by polymerization to low molecular weight 12 Sinclair RG, Copolymers of D,L-lactide and epsilon capro-
prepolymer, which is then catalytically converted to lactone. US Patent 4057537 (1977). (see also US Patent
dilactide and the purified dilactide is recovered in 4045418).
a distillation system with partial condensation and 13 Mark H and Whitby GS, eds, Collected Papers for Wallace Hume
Carothers on High Polymeric Substances. Interscience, New
recycling. The dilactide can be used to make high
York, pp. 142–144 (1940).
molecular weight polymers and copolymers. The pro- 14 Lowe CS, Preparation of high molecular weight polyhydroxy-
cess has been shown to use fermentation-derived lactic acetic ester. US Patent 2668162 (1954).
acid and the claimed ability to recycle and reuse the 15 Opre JE, Bergemann EP and Henneberry M, Environmentally
acid and prepolymers could make such a process very friendly solvent. US Patent 6191087 (2001).
16 Henneberry M, Snively JA, Vasek GJ and Datta R, Biosolvent
efficient and economic. Currently, Natureworks LLC
composition of lactate ester and D-limonene with improved
is the leader in the lactic polymer technology and cleaning and solvating properties. US Patent 6797684 (2004).
markets and the development and implementation 17 Chang J, Biosolvents on verge of breaking out with new
of their dilactide technology has contributed to their replacement applications, Chem Mark Rep 267:4 (2002).

1128 J Chem Technol Biotechnol 81:1119–1129 (2006)

DOI: 10.1002/jctb
 Lactic acid

18 Datta R, Tsai SP, Bonsignore P, Moon SH and Frank JR, 30 Porro D, Bianchi MM, Brambilla L, Menghini R, Bolzani D,
Technological and economic potential of poly(lactic acid) Carrera V, et al., Replacement of a metabolic pathway for
and lactic acid derivatives. FEMS Microbiol Rev 16:221–231 large-scale production of lactic acid from engineered yeasts.
(1995). Appl Environ Microbiol, 65:4211–4215 (1999).
19 Adkins H and Billica HR, The hydrogenation of esters to 31 Patnail R, Louie S, Gavvilovic V, Perry K, Stemmer WPC,
alcohols. J Am Chem Soc 70:3121–3125 (1948). Ryan CM, et al., Genome shuffling of Lactobacillus for
20 Bowden E and Adkins H, Hydrogenation of optically active improved acid tolerance. Nat Biotechnol 20:707–712 (2002).
compounds over nickel and copper–chromium oxide. J Am 32 Mani KN, Electrodialysis water splitting technology. J Mem-
Chem Soc 56:689–691 (1934). brane Sci. 58:117–138 (1991).
21 Kipax J, Harris N, Turner K, Anthony B and Rathmell C, 33 Hanada F, Hirayama K, Ohmura N and Tanaka S, Bipolar
Production of alcohols by hydrogenolysis of esters. German membrane and method for its production. US patent 5221455
Patent 3443277 A1 (1985). (1993).
22 Kitson M and Williams PS, Alcohols production by hydrogena- 34 Gillery B, Bailly M and Bar D, Bipolar membrane electrodialy-
tion of carboxylic acids. US Patent 4777303 (1988). sis: the time has finally come! Presented at 16th International
23 Holmen RE, Production of acrylates by catalytic dehy- Forum on Applied Electrochemistry, Amelia Island Planta-
dration of lactic acid and alkyl lactates. US Patent tion, FL (2002).
2859240 (1958). 35 Datta R, Recovery and purification of lactate salts from
24 Sawicki RA, Catalyst for dehydration of lactic acid to acrylic whole fermentation broth by electrodialysis. US Patent
acid. US Patent 4729978 (1988). 4885247 (1989).
25 Weitz HM, Hartig J and Platz R, Manufacture of propylene 36 Glassner D and Datta R, Process for production and purification
oxide. US Patent 4158008 (1979). of lactic acid. European Patent EP0393818 (1990).
26 Fouquet G, Merger F and Baer K, Manufacture of propylene 37 Baniel AM, Eyal AM, Mizrahi J, Hazan B, Fisher RR, Kol-
oxide. US Patent 4226780 (1980). stad JJ, et al., Lactic acid production, separation and/or recov-
27 Prescott SC and Dunn CG, Lactic acid and other organic acids, ery process. US Patent 6472559 (2002).
in Industrial Microbiology, 3rd edn. McGraw-Hill, New York, 38 Bhatia KK, Atmospheric pressure process for preparing pure
pp. 271–292 (1959). cyclic esters. US Patent 4835293 (1989). (see also related US
28 Lactic acid production technology, in Biomass Process Handbook, Patents 5023349; 5023350; 5043458; 5091544; 5117008;
a Production/Economic Guide to 40 Chemical Processes That Use 5136057; 5138074).
Biomass as a Raw Material. Technical Insights, Fort Lee, NJ, 39 Datta R and Tsai SP, Esterification of fermentation-derived
pp 96–103 (1982). acids via pervaporation. US Patent 5723639 (1998).
29 Baronofsky JJ, Schreurs WJA and Kashket ER, Uncoupling by
acetic acid limits growth of and acetogenesis by Clostridium
thermoaceticum. Appl Environ Microbiol 48:1134–1139 (1984).

J Chem Technol Biotechnol 81:1119–1129 (2006) 1129

DOI: 10.1002/jctb