lactic acid: recent advances in products, processes and technologies — a review

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

ReviewLactic acid: recent advances in products,processes and technologies – a reviewRathin Datta∗ and Michael HenryEnergy Systems Division, Argonne National Laboratory, Argonne, IL 60439-4815, USA

Abstract: Lactic acid, the most widely occurring hydroxycarboxylic acid, is an enigmatic chemical. It wasdiscovered a long time ago and its use in food preservation and processing and as a specialty chemical has grownover the years with current production of about 120 000 t yr−1. Its potential as a major chemical feedstock, derivedfrom renewable carbohydrates by sustainable technologies, to make plastics, fibers, solvents and oxygenatedchemicals, had also been recognized. Recently, new technologies have emerged that can overcome major barriersin separations and purification and processing. Advances in electrodialysis (ED) and bipolar membranes and oneparticular process configuration termed the ‘double ED’ process, a specific combination of desalting ED followedby ‘water-splitting’ ED with bipolar membranes, has given very promising results, showing a strong potential for anefficient and economic process for recovery and purification of lactic acid without generating a salt waste. For theproduction of polymers, several advances in catalysts and process improvements have occurred in the technologyto produce dilactide and its polymerization to produce plastics and fibers by Natureworks LLC, which is the leaderin lactic polymer technology and markets. Other advances in esterification technology with pervaporation anddevelopment 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 beenexpended 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

INTRODUCTIONLactic acid (2-hydroxypropanoic acid), CH3CHOHCOOH [CAS 50-21-5], is the most widely occurringhydroxycarboxylic acid. It was first discovered in1780 by the Swedish chemist Scheele. Lactic acidis a naturally occurring organic acid that can beproduced by fermentation or chemical synthesis. Itis present in many foods both naturally or as a productof in situ microbial fermentation, as in sauerkraut,yogurt, buttermilk, sourdough breads and many otherfermented foods. Lactic acid is also a principalmetabolic intermediate in most living organisms, fromanaerobic prokaryotes to humans.

Although lactic acid is ubiquitous in nature and hasbeen produced as a fermentation by-product in manyindustries (for example, corn steep liquor, a principalby-product of the multi-million tons per year cornwet-milling industry, contains approximately 25 wt%lactic acid on a dry solids basis), it has not been a large-volume chemical. By 1990 its worldwide productionvolume had grown to approximately 40 000 t yr−1 withtwo significant producers, CCA Biochem in TheNetherlands, with subsidiaries in Brazil and Spain,and Sterling Chemicals in Texas City, TX, USA, asthe primary manufacturers.1 CCA used carbohydratefeedstocks and fermentation technology and Sterling

used a chemical technology. Thus lactic acid has beenconsidered a relatively mature fine chemical in thatonly its use in new applications, e.g. as a monomerin plastics or as an intermediate in the synthesis ofhigh-volume oxygenated chemicals, would cause asignificant increase in its anticipated demand.2 By2003, several major changes had occurred in theUSA. Sterling exited the lactic acid business andtwo new manufacturers, Archer Daniels Midland(ADM) and Cargill Dow (a joint venture between DowChemical Company and Cargill Corporation), enteredthe business, both using carbohydrate fermentationtechnology. In early 2005, Cargill bought out Dowfrom this joint venture and established NatureworksLLC as a wholly owned subsidiary. ADM’s focushas been on lactic acid and its derivatives forconventional and other uses whereas NatureworksLLC has been the primary leader in the lactic-basedpolymer business. In the Far East, Musashino has beenreportedly manufacturing lactic acid by carbohydratefermentation technology with Chinese partners. Thecurrent worldwide production (including polymeruses) is estimated to be around 120 000 t yr−1. Thus,in the last decade, lactic acid production has grownconsiderably, mainly owing to the development of new

∗ Correspondence to: Rathin Datta, Energy Systems Division, Argonne National Laboratory, Argonne, IL 60439-4815, USAE-mail: [email protected](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 primarilybased on carbohydrate fermentation.

PRODUCTS AND USES – TRADITIONALTraditionally, the principal use of lactic acid is infood and food-related applications, which in the USAaccounted for approximately 85% of the demand. Therest (∼15%) of the uses are for nonfood industrialapplications. Currently, with the development andcommercialization of the biopolymers, lactic aciduse has increased considerably and 20–30% of the2005 production is estimated to be in these newapplications. The current spot price, as posted in theChemical Marketing Reporter, of heat-stable lactic acidis about $0.70 lb−1. In the future and as discussed later,the growth of lactic acid is expected to come from thedevelopment of new, large-volume uses, particularlyas a feedstock for biodegradable polymers, ‘green’solvents and oxygenated chemicals

As a food acidulant, lactic acid has a mild acidictaste, in contrast to other food acids. It is nonvolatile,odorless and is classified GRAS for general-purposefood additives by the FDA in the USA and byother regulatory agencies elsewhere. It is a goodpreservative and pickling agent for sauerkraut, olivesand pickled vegetables. It is used as an acidulant,flavoring, pH buffering agent or inhibitor of bacterialspoilage in a wide variety of processed foods suchas candy, breads and bakery products, soft drinks,soups, sherbets, dairy products, beer, jams and jellies,mayonnaise, processed eggs and many other processedfoods, often in conjunction with other acidulants.3 Anemerging new use for lactic acid and its salts is in thedisinfection and packaging of carcasses, particularlythose of poultry and fish, where the addition ofaqueous solutions of lactic acid and its salts duringprocessing increases shelf-life and reduces the growthof anaerobic spoilage organisms such as Clostridiumbotulinum.4,5

A large fraction (>50%) of the lactic acid forfood-related uses goes to produce emulsifying agentsused in foods, particularly for bakery goods. Theemulsifying agents are esters of lactate salts withlonger chain fatty acids. Four important productsare calcium and sodium stearoyl-2-lactylate [CAS25 383-99-7], glyceryl lactostearate [CAS 1338-10-9] and glyceryl lactopalmitate [CAS 1335-49-5]. Ofthe stearoyl lactylates, the calcium salt [CAS 5793-94-2] is a good dough conditioner and the sodium salt isboth a conditioner and an emulsifier for yeast-leavenedbakery products. The glycerates and palmitates areused in prepared cake mixes and other bakery productsand in liquid shortenings. In prepared cake mixes, thepalmitate improves cake texture, whereas the stearateincreases cake volume and permits mixing tolerances.3

The manufacture of these emulsifiers requires heat-stable lactic acid; hence only the heat-stable foodgrade is used for this application.

Technical-grade lactic acid has long been in usein the leather tanning industry as an acidulant fordeliming hides and in vegetable tanning. In varioustextile-finishing operations and acid dying of wool,technical-grade lactic acid was used extensively.Cheaper inorganic acids are now more commonlyused in these applications. The future availability oflower cost lactic acid and the increasing environmentalrestrictions on waste salt disposal may reopen thesemarkets for lactic acid.

Traditionally, lactic acid is used in a wide variety ofsmall-scale, specialized industrial applications wherethe functional speciality of the molecule is desirable.Examples include pH adjustment of hardening bathsfor Cellophane used in food packaging, a terminatingagent for phenol-formaldehyde resins, alkyd resinmodifier, solder flux, lithographic and textile printingdevelopers, adhesive formulations, electroplating andelectropolishing baths and detergent builders (withmaleic anhydride to form carboxymethoxysuccinicacid-type compounds). Owing to the high cost and lowvolume of production, these applications accountedfor only 5–10% of the consumption of lactic acid.1

Lactic acid and ethyl lactate [CAS 97-64-3] havelong been used in pharmaceutical and cosmetic appli-cations and formulations, particularly in topical oint-ments, lotions, parenteral solutions and biodegradablepolymers for medical applications such as surgicalsutures, controlled-release drugs and prostheses. Asubstantial part of pharmaceutical lactic acid is used asthe sodium salt [CAS 16595-31-6] for parenteral anddialysis applications. The calcium salt [CAS 5743-48-6] is widely used for calcium deficiency therapyand as an effective anti-caries agent. As humectants incosmetic applications, the lactates are often superioras natural products and more effective than polyols.3

Ethyl lactate is the active ingredient in many anti-acne preparations. The use of the chirality of lacticacid for synthesis of drugs and agrochemicals is anopportunity for new applications for optically activelactic acid or its esters. The chiral synthesis routes toR-(+)-phenoxypropionic acid [CAS 1129-46-0] andits derivatives using S-(−)-lactate ester as a chiralsynthon have been described.3 These compounds areused in herbicide production. Another use, as an opti-cally active liquid crystal using lactic acid as a chiralsynthon, has been described.6 These advances openup new small-volume specialty chemical opportunitiesfor optically active lactic acid and its derivatives.

PRODUCTS AND USES – RECENTDEVELOPMENTSIts two functional groups permit a wide variety ofchemical reactions for lactic acid. The primary classesof these reactions are condensation, esterification,reduction and substitution at the alcohol group.7

Using such reactions, lactic acid can be used forproducts that potentially have very large-volume usesin industrial applications and consumer products.

1120 J Chem Technol Biotechnol 81:1119–1129 (2006)DOI: 10.1002/jctb

Lactic acid

Carbohydrates Lactic AcidFermentation &

Purification

Esterification Blending

Bio-basedSolvents

Ethyl Lactate(Lactate Esters)

BiosolventBlends

CatalyticDistillation

Dilactide Polymerization PlasticsFibers

Hydrogenolysis PropyleneGlycol

Dehydration PropyleneOxide

CatalyticDehydration

Acrylic AcidAcrylate Ester

Alcohol

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

The primary classes of such products are polymersfor plastics and fibers, solvents for formulations andcleaning and oxygenated industrial chemicals. Thuslactic acid is one of the primary platform chemicalsthat can be derived from renewable carbohydrates andused to make a wide variety of useful products. Thisis shown schematically in Fig. 1.

PolymersBecause lactic acid has both hydroxyl and carboxylfunctional groups, it undergoes intramolecular or self-esterification and forms linear polyesters, lactoyllacticacid and higher poly(lactic acid)s or the cyclicdimer 3,6-dimethyl-p-dioxane-2,5-dione [CAS 95-96-5] (dilactide). Whereas the linear polyesters,lactoyllactic acid and poly(lactic acid)s are producedunder typical condensation conditions such as byremoval of water in the presence of acidic catalysts, theformation of dilactide with high yield and selectivityrequires the use of special catalysts which are primarilyweakly basic. The use of tin and zinc oxides andorganostannates and -titanates for this purpose hasbeen reported.7–10

2 CH3CHOHCOOH C6H8O4 + 2 H2O

OH

O

OH

Lactic acid

O

O O

O

+H

OH

Water

2 2

Dilactide

(1)

Dilactide, also commonly termed lactide, is theprimary feedstock for polymerization to make highmolecular weight polymers of lactic acid (PLA), which

are biodegradable thermoplastics. The L-isomer oflactic acid is the preferred feedstock for dilactideproduction because it provides a high dilactideyield and a high molecular weight polymer witha high degree of crystallinity and tensile strength.Furthermore, a fairly wide range of propertiescan be obtained by copolymerization with otheroxygenated functional monomers such as glycolide,caprolactone, polyether polyols and the D-isomer oflactic acid. The actual compositions of the polymersare proprietary to the various manufacturers. Thepolymers are transparent, which is important forpackaging applications. They offer good shelf-lifebecause they degrade slowly by hydrolysis, whichcan be controlled by adjusting the compositionand molecular weight. The properties of lacticcopolymers, which approach those of large-volumepetroleum-derived polymers such as polystyrene,flexible poly(vinyl chloride) (PVC) and vinylidenechloride, have been summarized.2 There are numerouspatents and articles on lactic acid polymers andcopolymers, their properties, potential uses andprocesses, including some that date back to the earlywork by Carothers at Du Pont and other DuPontresearchers.2,11–14

Currently, Natureworks LLC (www.natureworks-llc.com) is the primary developer and commercializerof lactic acid-based polymers and products, anda recent patent search showed that over 100US patents in this area were assigned to thiscompany. The company produces and sells twotypes of products – the polydilactide-based resins(Natureworks PLA), used for plastics/packagingapplications, and the Ingeo polydilactide-basedfibers, that are used in specialty textiles and fiberapplications. Over the past 10 years, this company

J Chem Technol Biotechnol 81:1119–1129 (2006) 1121DOI: 10.1002/jctb

R Datta, M Henry

has done extensive product development work, themagnitude of which becomes apparent from theirtechnical and applications literature. They have alsobuilt a plant in Blair, Nebraska, with a nameplatecapacity of 300 million lb yr−1 for the production oflactic acid and PLA. For product commercializationthey have partnered with many potential end-usersand polymer processing equipment manufacturers.

For plastics and packaging applications, bothgeneral and detailed information on the propertiesof various grades of resins are available from themanufacturer. A variety of products such as cups,cutlery, plates and saucers and food dispensingcontainers can be made by injection molding. Generaland detailed guides for injection molding process usingconventional injection molding equipment with PLAresins are also available from the manufacturer. Someof the advantages listed include superior clarity, goodheat deflection, readily degradable in the enviornment(compostable) and sustainability (renewable resourcebased). The US FDA and European regulatoryauthorities have approved the resins for all food-typeapplications.

Similarly, for fiber and fabric applications compar-ative properties of the PLA-based Ingeo with nylon,PET, rayon, cotton, silk and wool are available fromthe company.

Some of the advantages listed include:

• lower specific gravity than other natural fibers –lighter products;

• higher tenacity than natural fibers – tensile strength;• significantly lower moisture regain than natural

fibers – easier drying after wet;• outstanding UV resistance compared with all fibers;• low refractive index, which produces intense colors

on dyeing;• compared with PET and other synthetics, lower

heat of combustion, less smoke when burned, highwater wicking and faster moisture spread.

Some of the negatives include:

• poor alkali resistance, causing strength loss in theconventional dispersed dye process;

• low ironing temperature due to low crystalline melttemperature.

Thus, over the past 10 years, an extensive amount ofwork has been done on developing and commercializ-ing PLA and its products. A more detailed analysis ofpolymer technology undertaking is beyond the scopeof this paper.

SolventsEnvironmentally friendly, ‘green’ solvents are anotherpotential growth area for lactic acid derivatives, partic-ularly lactate esters of low molecular weight alcoholssuch as ethyl, propyl and butyl lactate. Purac Inc.has developed and commercialized several special-ized applications of lactate esters in electronics and

precision cleaning. More recently, Vertec BiosolventsInc. (www.vertecbiosolvents.com) has been develop-ing and commercializing blends of these esters withother biologically derived solvents such as fatty acidmethyl esters or D-limonene that can have a wide rangeof solvating and cleaning properties.15,16 The US Envi-ronmental Protection Agency (EPA) recently classifiedthe lactate esters ethyl and butyl lactate as Class 4Ainert ingredient for use in the formulation of pesticidesand other bioactive compounds. The Class 4A desig-nation is given to compounds that have demonstratednegligible toxicity and an excellent environmental pro-file. Thus, a good range of specialty applications andcommercial uses could be developed with these non-toxic, environmentally friendly lactate ester solventswith other biologically derived solvents.17

Oxygenated chemicalsLarge-volume oxygenated chemicals such as propyleneglycol (1.5 billion lb US production in 2004),propylene oxide (4 billion lb US production in 2004),acrylic acid and acrylate esters (1.8 billion lb USproduction in 2004) and other chemical intermediatessuch as lactate ester plasticizers can potentially bemade from lactic acid.1,2,18 The advances made inhydrogenolysis technology can be further developedand integrated to make propylene glycol from lacticacid in the future.19–22

CH3CHOHCOOH + 2 H2 CH3CHOHCH2OH + 2 H2O

OH

O

OH

Lactic acid

+ 2

Hydrogen

OHHO

Propylene glycol

+ 2H

OH

Water

H H

(2)

Advances in catalysis and process technologies areneeded for efficient conversion of lactate to acrylateor propylene glycol to propylene oxide, even thoughsome of the early patents show the technical feasibilityof such conversions.23–26

CH3CHOHCH2OH CH3CHOCH2 + H2O

O

Propylene oxide

OHHOPropylene glycol

+H

OH

Water

(3)

CH3CHOHCOOH CH2CHCOOH + H2O

OH

O

OH

Lactic acid

O

OH

Acrylic acid

+H

OH

Water

(4)

In Table 1, these potential products and applica-tions and estimates of their overall size in terms of both


Lactic acid

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

Products Uses

US marketvolume

(billion lb yr−1)

World marketvolumea

(million t yr−1)

Sellingprice ($ lb−1)

[$ t−1]Valuef

($million yr−1)

Polymers: plastics Degradable packaging, films 1.5 1.5 1.0c [2200] 3300Polymers: fibers Specialty textiles, bedding, etc. 0.5 0.5 2c [4400] 2200‘Green’ solvents (biosolvent

blends)Specialty formulations, industrial/

machinery cleaning, etc.0.5b 0.5 1b [2200] 1100

Oxychemicals: propylene glycol Humectants, food processing,deicers, polymers

1.5 1.5 1d [2200] 3300

Oxychemicals: propylene oxide Polyurethanes, plastics, etc. 4.0e 4.0 0.9d [2000] 8000Oxychemicals: acrylates Polymers, plastic films, coatings 1.8 1.8 1d [2200] 4000Total 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.For the oxygenated chemicals which are known com-modities, the product volumes and prices have beentaken from commercial journals such as the Chemi-cal Marketing Reporter and other sources such as theStanford Research Institute (SRI) Chemical EconomicHandbook (CEH) reports. For the polymers and sol-vents we have derived our estimates from many recentnews reports, topical reports and announcements.

In summary, lactic acid has a very large potential tobe a major ‘platform’ chemical that can be used forpolymers – plastics and fibers; solvents – formulationsand cleaning and three-carbon oxygenated chem-icals that are used in large quantities for manyapplications. Recently, considerable pioneering effortin product development and commercialization hasbeen invested by a few companies and considerablymore is needed. Real support from consumer, regu-latory and government organizations is also neededto overcome the inertia and barriers to change tosustainable products from renewable resources. Fur-thermore, the lactic acid production technologies alsoneed to be further advanced and implemented tobecome technically and economically feasible andenvironmentally sound. This is discussed furtherbelow.

MANUFACTURING TECHNOLOGIESWe will focus on the manufacturing technologies forthe production of purified lactic acid and key interme-diates such as esters and other derivatives. Discussionsand analysis of the advances in polymerization tech-nologies with the PLA resins are beyond the scopeof this review. First, the traditional technologies forlactic acid production and their limitations are brieflydiscussed. Following that, some promising emergingtechnologies, particularly in the fields of separationsand purification, are discussed.

Traditional technologiesLactic acid can be manufactured either by chemicalsynthesis or by carbohydrate fermentation; both havebeen used for commercial production in the past. Inthe USA, lactic acid was manufactured synthetically bySterling Chemicals using the lactonitrile route, whichwas a byproduct of acrylonitrile technology. Sterlingexited the business in the early 1990s. In the Far East,Musashino Chemical used this technology for some ofits production but recently converted to fermentativeproduction. The synthetic route had many majorlimitations that included limited capacity because ofthe tie to a byproduct of another process, inability tomake the desirable L-lactic acid stereoisomer only andhigh manufacturing costs.

Currently, all lactic acid manufacture is based oncarbohydrate fermentation and the major manufactur-ers are CCA Biochemical BV of The Netherlands withplants in Europe, Brazil and USA, Archer DanielsMidland (ADM) in the USA, Musashino in the FarEast and Natureworks LLC, which has been the pri-mary leader in the lactic-based polymer business.

The existing commercial production processes usehomolactic organisms such as Lactobacillus delbrueckii,L. amylophilus, L. bulgaricus and L. leichmanii. Mutantfungal strains of Aspergillus niger are also reportedlyused. A wide variety of carbohydrate sources, e.g.molasses, corn syrup, whey, dextrose and cane or beetsugar, can be used. The use of a specific carbohydratefeedstock depends on the price, availability and itspurity. Proteinaceous and other complex nutrientsrequired by the organisms are provided by cornsteep liquor, yeast extract, soy hydrolysate, etc.Excess calcium hydroxide/carbonate is added to thefermenters to neutralize the acid, maintaining the pHaround 5–6, and produce a calcium salt of the acid inthe broth. The fermentation is conducted in a batchor fed-batch mode, taking 2–4 days to complete, andlactate yields of approximately 90 wt% from a dextrose


R Datta, M Henry

equivalent of carbohydrate are obtained. It is usuallydesired to keep the calcium lactate in solution sothat it can be easily handled with the cell biomassand other insolubles and the final concentrationachieved is around 10 wt%. The calcium lactate-containing broth is filtered to remove cells, carbontreated, evaporated and acidified with sulfuric acid toconvert the salt into lactic acid and insoluble calciumsulfate, which is removed by filtration. The filtratecan be further purified using carbon columns and ionexchange and evaporated to produce technical- gradelactic acid, but not a high-purity, heat-stable product,which is required for the stearoyl lactylates, polymers,solvents and other value-added applications. For thehigh-purity product, the technical-grade lactic acidis esterified with methanol or ethanol and the esteris recovered by distillation, hydrolyzed with water,evaporated and the alcohol recycled. This separationprocess produces a highly pure product which is water-white and heat stable.

C6H12O6 −−−→ 2 CH3CHOHCOOH

(5a)

2 CH3CHOHCOOH+Ca(OH)2

−−−→ Ca(CH3CHOHCOO)2

+2 H2O

(5b)

Ca(CH3CHOHCOO)2

+H2SO4−−−→ 2 CH3CHOHCOOH

+CaSO4

(5c)

Some of the economic hurdles and process costcenters of this conventional carbohydrate fermentationprocess, shown schematically in Fig. 2, are in thecomplex separation steps which are needed to recoverand purify the product from the crude fermentationbroths. Furthermore, approximately 1 t of crudegypsum, CaSO4, is produced and as a waste byproductneeds to be disposed of for every ton of lacticacid produced by the conventional fermentationand recovery process.27,28 These factors have madelarge-scale production by this conventional routeeconomically and ecologically unattractive.

Emerging technologiesThe primary technology barriers to cost-effective pro-duction of lactic acid are in separations and purifi-cation. One major barrier is the ‘cation elimination’or the ‘salt’ problem. The fermentation operates mostefficiently and effectively at near neutral pH, whichrequires neutralization and produces the salt of the acidinstead of the acid itself. This is true for many otheranaerobic acidogenic fermentations such as acetate,succinate, propionate, butyrate and others, which havehigh yields but low metabolic activity when the pH islow. Even for fungal fermentations for lactic acid,pH tolerance is not good and salts are predominantlyproduced.

This pH intolerance barrier for anaerobic acido-genic bioconversions is fundamental and is due to

Sterilization

AnaerobicFermentation

Acidulation

Rotary DrumFiltration

Evaporation

EsterificationReactor/Column

Ethanol Column

Lights Column

Carbohydrate

Sulfuric Acid

Ethanol

Purified Lactic Acid

Ester Column

Filter Aid Filter Press

"WasteGypsum"

Waste Purge

Lights Purge

Heavy Impurities Purge

Mol

. Sie

veD

ehyd

ratin

g

NeutralizationAgent (Lime)

IX HydrolysisEthanol Recycle

Water

Nutrients

Figure 2. Conventional process for lactic acid manufacture fromcarbohydrate.

bioenergetics. Electrons or reducing equivalents areconserved in anaerobic bioconversions and the achiev-able yields are therefore near theoretical values. Forexample, the theoretical yield of lactate from dex-trose is 100% (w/w) or 2 mol per mole. However, themetabolic energy obtained is fairly low, enough forcell growth and also non-growth associated productformation, but not enough for maintaining a protongradient between the cell and its external environment.This leads to free diffusion of the protonated acid intothe cell and cessation of metabolic activity. This wasconclusively established by several laboratories in themid-1980s, including the present author’s (R.D.) lab-oratory at Corn Products Corporation. and results ofthe metabolic studies were published.29 One way toincrease the metabolic energy obtained would be toconduct the bioconversion under oxidative conditions,but then the electrons would not be conserved andyields would be significantly lower. This conundrum,based on fundamental bioenergetics, was recognizedby several research teams and organizations, whichfocused their efforts on initiating and developing noveland advanced separation technologies that might over-come this ‘salt’ problem.

Recent results of genetic engineering work withyeasts to make lactic acid producers or genomeshuffling of Lactobacillus for increasing acid tolerancehave been published30,31 and these do not show


Lactic acid

any significant advance in overcoming this problem.In the work published by the large team ledby Porro,30 Kluyveromyces lactis yeast strain wasgenetically engineered to become a homolactateproducer. In actual fermentation tests at a low finalpH of 2.8–3.0, the organism was able to produce onlyabout 30 g L−1 of protonated lactic acid with yields ofabout 0.7–0.9 mol per mole of dextrose, which is only35–45% of theoretical, uneconomic for a commercialprocess.

Hence technologies that would allow the conversionof the salt to the corresponding acid and alkaliwithout consuming another acid or large amount ofenergy have been critical. The other problems arein purification, where the efficient production of akey intermediate such as an ester with high yield andpurity is very important. Recent advances are discussedbelow.

Advanced electrodialysis technologiesAdvances in membrane-based separation and purifi-cation technologies, particularly in microfiltration,ultrafiltration and electrodialysis (ED), have led to theinception of new processes for lactic acid productionthat do not produce a salt waste. Successful com-mercial development of bipolar ED membranes hasrecently occurred.32–34 These membranes can splitand separate water to protons (H+) and hydroxyl(OH−) ions as shown schematically in Fig. 3 and themembranes can operate at about 80% of the theoret-ical thermodynamic efficiency.33,34 This technologyadvance now enables the H+ to transport to the acidanion to form the free acid and the OH− ion to trans-port to the cation compartment to form the free base.Despite the recent advances in bipolar membranes,they have the fundamental problem of intoleranceto multivalent cations such as calcium and magne-sium that form insoluble hydroxides at the criticalinterface of the bipolar membrane where the ions sep-arate. Typically, the tolerance limit for these divalentcations is about 1 ppm. Fermentation broths containmuch higher concentrations, often in the region of1000 ppm. Hence a successful process with bipolarmembranes requires critical integration of key processsteps that would work efficiently and economically.

+

H++

OH-

H2O

H+

OH-A - Anion permselective layerC - Cation permselective layerI - Interface layer

A C

-

I

Figure 3. Bipolar electrodialysis membrane schematic and operation.

One particular process configuration, termed the‘double ED’ process, (Fig. 4), has been developed andpiloted at Michigan Biotechnology Institute (MBI)and at Argonne National Laboratory (ANL) and hasgiven very promising results.35,36 This process uses adesalting ED unit to remove the multivalent cationsand concentrate the lactate salt, followed by a ‘water-splitting’ ED unit with bipolar membranes to produceconcentrated lactic acid and alkali for recycle.

The desalting ED (shown schematically in Fig. 5)is a critical step that enables the process to operateefficiently and economically. This step:

• Concentrates the lactate salt by 2-fold or higher,from a feed broth concentration of 8–10 to about20 wt%.

• Purifies the product (10–20 fold purification onproteins, peptides, sugars and other non-ionicimpurities).

• Rejects divalent ions by 98–99% (using monovalentcation selective membranes).

Fermentation

MicroporousFiltration

DesaltingElectrodialysis

Chelation

Water-SplittingElectrodialysis

PolishingIon Exchange

Evaporation

Esterification

Distillation/Hydrolysis

Purified Lactic Acid

Dextrose

Ammonium Lactate Broth

AmmoniaRecycle

Lactic Acid

Ethanol Makeup

Ethanol,Recycle

Ammonia Makeup

Figure 4. Double-ED process schematic.


R Datta, M Henry

CCCC AA A

X-

M+

OM++

Concentrated Product(Ammonium Lactate)

Desalted Broth (Recycle)

AN

OD

E

Anolyte

CA

TH

OD

E

Catholyte

A - Anion exchange membraneC - Cation exchange membraneM+X-

- Lactate salt (M+ = NH4+, X- = CH3CHOHCOO-)

M++ - Divalent/Multivalent Cations

O - Non-ionized or weakly ionized components

+ -

Feed Broth (Ammonium Lactate)

M+X-

OM++

X- X-

X-- X--

M+ M+

M+X-

OM++

M+X-

OM++

OM++

OM++

Figure 5. Desalting ED operation schematic.

CCCC B

OH-

M+

X-

M+X-

Alkali(Ammonium Hydroxide)

Lactic Acid

AN

OD

E

Anolyte

CA

TH

OD

E

Catholyte

C - Cation exchange membraneB - Bipolar membraneM+X- - Lactate salt (M+ = NH4

+, X- = CH3CHOHCOO-)H+ - Hydrogen ionsOH- - Hydroxide ions

-+

Concentrated Product Feed(Ammonium Lactate)

M+X- M+X-

H+

OH-

M+

X-H+

OH-

M+

X-H+

H+X-

B B

Figure 6. Water-splitting ED operation schematic.

• Has a high recovery yield (>95% yield of lactate tothe product from the feed).

• Moreover, the power consumption to do all of thisis low, approximately 0.33 kWh kg−1 (0.15 kWhlb−1) of lactate and allows a high current density tobe maintained.

All of these benefits make the overall processefficiency and economics attractive. The increase inconcentration decreases the subsequent evaporationenergy load by half, the purification decreases thecosts of downstream purification steps, the divalent ionremoval is particularly important because it reducesthe Ca2+ and M2+ concentrations in the product

stream to the range of 5–10 ppm and reduces theneed for chelation by >95%.

The water-splitting ED step using the two-compartment ‘cation-bilpolar’ configuration (shownschematically in Fig. 6) also permits efficient andeconomic operation. This step can achieve:

• Low power consumption [0.55 kWh kg−1 (0.25kWh lb−1) of lactic acid].

• High current density (1000 A m−2).• High (99%) acidification of the lactate salt.• Reduced fouling and long membrane life because

organic foulants are exposed to the cation mem-branes only, which have much lower fouling ten-dency than anion membranes.


Lactic acid

• The alkali stream containing the aqueous ammoniacan be readily stripped and the concentratedaqueous ammonia recycled.

The feasibility of the ‘double ED’ process hasbeen shown at the pilot scale using a slip streamof lactate broth from an industrial fermentationprocess. The process has been shown to provide theperformance parameters that have been summarizedabove. Moreover, successful resolution of some criticallong-term stability issues has also been demonstrated.The desalting ED process has been operated forover 700 h with recycle. Over 350 clean-in-place(CIP) cycles have been conducted with no significantdecrease in membrane integrity or performance. Thewater-splitting ED unit has been operated on thedesalting ED product for over 1000 h with recycleproducing a steady stream of the lactic acid and alkali.During these operations, a great deal of performancedata and analysis of the membrane materials werecollected and showed no evidence of membranedeterioration or loss of function. Hence the advancesin electrodialysis technology and using the particularconfiguration of the ‘double ED’ process describedhere have a strong potential to provide an efficientand economic process for recovery and purificationof fermentation-derived lactic acid without generatingsalt waste.

Other technologies for recovery and saltelimination (non-ED)Other schemes without using electrodialysis have alsobeen attempted.

Ecochem Inc., a Du Pont–Conagra partnership,had developed a recovery and purification processthat produced a by-product ammonium salt instead ofinsoluble gypsum cake and the company intended tosell this as a low-cost fertilizer. A demonstration-scaleplant based on whey feedstock had been completed toprove the process but the process was not successfulowing to several major separation problems and theenterprise was abandoned.

Cargill Dow, the primary developer of lactic poly-mer technology and products, had been developing analternative process based on tertiary amine/carbonatetechnology.37 In this process, sodium lactate is pro-duced by fermentation and the broth is concentratedand extracted with a tertiary amine solvent mixtureunder CO2 pressure to produce and precipitate asodium bicarbonate salt and an amine lactic acidextract. This is back-extracted with hot water at 140 ◦Cand 100 psig to produce a lactic acid solution and aregenerated amine solvent mixture that is recycled.The lactic acid can be further purified and convertedto the dilactide for polymer manufacture. The sodiumbicarbonate is further heated to produce sodium car-bonate and CO2, which are recycled into the process.Several years ago, Cargill Dow built a manufacturingplant for lactic polymers with a carbohydrate front end,but how much of this alternative lactic acid productiontechnology is being used has not been divulged.

Purification technologiesEfficient purification technologies that give high yieldand purity for the key intermediates such as dilactideand lactate esters are also very important and tworecent advances are highlighted.

For the production of polymers or other derivatives,the technology to produce dilactide (the internaldiester) is critically important. Several advances incatalysis and process improvements have occurred andproprietary technologies have been developed. In themany patents issued to Cargill Inc., the development ofcontinuous processes for the manufacture of dilactidepolymers with controlled optical purity from purifiedlactic acid is described.10 The processes uses aconfiguration of multistage evaporation followed bypolymerization to a low molecular weight prepolymer,which is then catalytically converted to dilactide withthe purified dilactide being recovered in a distillationsystem by partial condensation and recycling. Thedilactide can be used to make high molecular weightpolymers and copolymers. The process has beenable to use fermentation-derived lactic acid andthe claimed ability to recycle and reuse the acidand prepolymers could make such a process veryefficient and economic.10 In a patent issued to DuPont,35 a process to make cyclic esters, dilactide andglycolide from their corresponding acid or prepolymeris described. This process uses an inert gas suchas nitrogen to sweep away the cyclic esters fromthe reaction mass and then recovers and purifiesthe volatilized cyclic ester by scrubbing with anappropriate organic liquid and separates the cyclicester from the liquid by precipitation or crystallizationand filtration of the solids. High-purity dilactide withminimal losses, due to racemization, has been claimedas an advantage for this process. Recycling and reuseof the lactic moiety in the various process streams havebeen claimed to be feasible.38 Currently, NatureworksLLC is the leader in the lactic polymer technology andmarkets and the development and implementationof their dilactide technology has contributed to theirsuccess.

In a recent patent, a process based on pervaporation-assisted esterification of ammonium lactate to ethyllactate is described. This process is being furtherdeveloped with membranes that selectively permeatewater vapor and ammonia over ethanol and the esterand thus provide good selectivity and yield.39 Theaqueous ammonia can be recycled to the fermenter forneutralization of the acid produced and the ester canbe further purified by distillation. If successful, thistechnology could lead to an efficient and economicprocess to make purified lactate esters such as ethyllactate that are useful as solvents or in solvent blendsand can also be used to make purified lactic acid.

Technologies for other derivatives and chemicalsHydrogenolysis reaction technology designed toproduce alcohols from organic acids or estershas also advanced recently; new catalysts and


R Datta, M Henry

processes give high selectivity and rates and operateat moderate pressures.21,22 This technology hasbeen commercialized to produce 1,4-butanediol,tetrahydrofuran and other four-carbon chemicalintermediates from maleic anhydride. In the future,such technologies could be integrated with low-costlactic acid production processes to make propyleneglycol and other intermediate chemicals.21,22

Further advances in catalytic dehydration and pro-cess technologies are needed for efficient conversionof lactate to acrylate or propylene glycol to propyleneoxide, even though some of the early patents show thetechnical feasibility of such conversions.23–26

CONCLUSIONSLactic acid is an enigmatic chemical. It was discovereda long time ago and has been produced as a specialtychemical for decades. Its use in food preservation andprocessing has grown over the years. Its potential asa major chemical feedstock, derived from renewablecarbohydrates by sustainable technologies, to makeplastics, fibers, solvents, oxygenated chemicals, etc.,had also been recognized.1,2,18

Only recently, however, have new technologiesemerged that can overcome major barriers in sep-arations and purification and processing. Advancesin membrane-based separation and purification tech-nologies, particularly in micro- and ultrafiltration andelectrodialysis and bipolar membranes (ED), have ledto the inception of new processes for lactic acid pro-duction. One particular process configuration, termedthe ‘double ED’ process, which is a specific combi-nation of desalting ED followed by ‘water-splitting’ED with bipolar membranes, has given very promisingresults and has a strong potential to provide an efficientand economic process for the recovery and purificationof fermentation-derived lactic acid without generatingsalt waste. For the production of polymers or otherderivatives, the technology to produce the dilactideinternal diester is critically important. Several advancesin catalysts and process improvements have occurredand, in the many patents issued to Cargill Inc., thedevelopment of continuous processes for the manu-facture of dilactide polymers with controlled opticalpurity from purified lactic acid is described. The pro-cesses use a configuration of multistage evaporationfollowed by polymerization to low molecular weightprepolymer, which is then catalytically converted todilactide and the purified dilactide is recovered ina distillation system with partial condensation andrecycling. The dilactide can be used to make highmolecular weight polymers and copolymers. The pro-cess has been shown to use fermentation-derived lacticacid and the claimed ability to recycle and reuse theacid and prepolymers could make such a process veryefficient and economic. Currently, Natureworks LLCis the leader in the lactic polymer technology andmarkets and the development and implementationof their dilactide technology has contributed to their

success. Other advances in esterification technologywith pervaporation and development of biosolventblends also have a high potential for use as ‘green’solvents in many applications.

Hence, from a technology viewpoint, majoradvances and integration of bioprocessing, biochem-ical engineering, advanced membrane-based separa-tions technologies, chemical catalysis and polymerprocessing have developed to bring out the poten-tial of lactic acid. Recently, a considerable amountof pioneering effort in technology, product develop-ment and commercialization has been expended byseveral companies and considerably more is needed.Furthermore, real support from consumer, regula-tory and government organizations is also neededto overcome the inertia and barriers to change thatare so inherent in bringing out sustainable productsfrom renewable resources to replace long-establishedpetroleum-derived products.

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25 Weitz HM, Hartig J and Platz R, Manufacture of propyleneoxide. US Patent 4158008 (1979).

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lactic acid: recent advances in products, processes and technologies — a review

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