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Separation and Purification Technology 52 (2006) 117

Review

Comparative assessment of downstream processing options for lactic acid

H.G. Joglekar , Imran Rahman, Suresh Babu, B.D. Kulkarni, Ajit Joshi

Chemical Engineering and Process Development Division, National Chemical Laboratory (NCL), Pune-411008, India

Received 14 October 2005; received in revised form 20 March 2006; accepted 20 March 2006

Abstract

The possibility of manufacturing a biodegradable polymer from lactic acid has led to extensive research in recovery of lactic acid produced

by fermentation, by different downstream processing routes. This paper assesses the suitability of different downstream processing options suchas reactive extraction, adsorption, electrodialysis, esterification and reactive distillation. It compares the costs of different process routes. The

assessment indicates that the conventional precipitation of calcium lactate, followed by acidification, esterification and hydrolysis will be the most

economical route although it generates large quantity of gypsum sludge.

2006 Elsevier B.V. All rights reserved.

Keywords: Lactic acid; Reactive extraction; Adsorption; Electrodialysis; Esterification; Reactive distillation

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

1.1. Objective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

1.2. Global scenario . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21.3. Polylactic acid/bio-degradable plastics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

1.4. Lactic acid production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

1.5. Source of carbohydrates for fermentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

1.6. Fermentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

1.7. Downstream processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

2. Reactive extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

2.1. Extractant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

2.2. Diluents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

2.2.1. Choice of diluents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

2.3. Effect of extractants, diluents and pH on distribution coefficient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

2.4. Third phase formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

2.5. Complex formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

2.6. Re-extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

2.6.1. Using NaOH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

2.6.2. Using HCl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

2.6.3. Temperature-swing regeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

2.6.4. Using trimethyl amine (TMA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

2.6.5. Diluent swing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

2.7. Choice of extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

3. Adsorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

3.1. Reported research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

3.2. Choice of adsorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Corresponding author. Tel.: +91 20 25902420; fax: +91 20 25902675.

E-mail address: [email protected] (H.G. Joglekar).

1383-5866/$ see front matter 2006 Elsevier B.V. All rights reserved.

doi:10.1016/j.seppur.2006.03.015


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2 H.G. Joglekar et al. / Separation and Purification Technology 52 (2006) 117

4. Electrodialysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

4.1. Reported research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

4.2. Choice of electrodialysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

5. Esterification and reactive distillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

5.1. Reported research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

5.2. Choice for esterification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146. Possible downstream process routes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

7. Future direction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

8. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

1. Introduction

1.1. Objective

Lactic acid is a simple compound containing both the

hydroxyl and carboxylic acid groups, which permit it to par-ticipate in many interesting and valuable chemical reactions.

Among the known reactions of lactic acid the dehydration to

acrylic acid, the polymerization to poly(lactic acid) and conden-

sation to 2,3-pentanedione are potentially the most profitable

pathways. The viability of making an inexpensive biodegradable

polymer poly(lactic acid) from lactic acid has sparked exten-

sive interest andresearch in the area of producing andrecovering

relatively pure lactic acid. This paper is to assess various down-

stream processing options studied by researchers and identify

affordable process route for manufacturing lactic acid, which is

sufficiently pure for polymerization.

1.2. Global scenario

Lactic acid is currently being produced by number of compa-

nies around the world, but it is only used in limited applications

in the food, flavor as preservative, in cosmetics, leather process-

ing, and pharmaceuticals industries. Lactic acid of higher purity

or without certain impurities is required for polymerization.

The possibility of producing a high volume of inexpensive

lactic acid also has lead to research using lactic acid as an

alternative feedstock for the production of many speciality and

commodity chemicals such as acrylic acid, propionic acid, 2,3-

pentanedione, pyruvic acid and propylene glycol.

The world market of lactic acid is growing every year. Thelevel of production is around 350 millions kg per year [1] and the

worldwide growth is believed by some observers to be 1215%

per year [2].

1.3. Polylactic acid/bio-degradable plastics

The main application field of lactic acid polymer has been

medical applications, fibres, packaging materials and as sol-

vents. These medical applications include its usage utilizing

different properties in terms of tensile strength, viscosity, purity

etc. l-Lactic acid polymer exist in three different forms that can

be used for filling the gaps in bones, solid with tensile strengthto produce sutures (stitching material), and the glue form that

is mainly applied in joining membranes or thin skins in humans

[3]. Another important property of poly lactic acid is its high

strength against ultraviolet (UV) radiation [4].

Polylactic acid has a potential to provide a new product plat-

form to compete with hydrocarbon-based thermoplastic. Poly-

lactic acid polymers have barrier properties similar to polyethy-

lene terephthalate (PET) and gloss, clarity and processabilitysimilar to polystyrene (PS). In addition, they provide heat stabil-

ity at lower temperatures than polyolefins and can be processed

by most melt fabrication techniques, including fiber spinning.

The research on lactic acid related materials have attracted

several universities and institutes in Europe, Asia and USA.

There are a number of small-scale production facilities of poly-

lactic acid. Dow Chemicals and Cargill have the largest poly-

lactide (PLA) producing company with an annual capacity of

140,000 tonnes located in Blair, USA [5].

The future of the polylactic acid depends upon the technol-

ogy efforts of lactic acid manufacturers to develop Polylactic

acid modified with other co-monomers, so as to compete with

polymers such as PETand PS,both on cost andapplicationbasis.

1.4. Lactic acid production

Lactic acid can be manufactured by either chemical synthe-

sis or by fermentation of renewable carbohydrates. Both these

methods are used for commercial production. While chemical

synthesis route produces only a racemic mixture of lactic acid, a

fermentation process can produce a stereoisomer of lactic acid.

Therefore, fermentation process is preferred for the production

of lactic acid and about 90% of lactic acid is produced by fer-

mentation route. Currently the fermentation is carried out in

the batch mode. A large number of carbohydrate materials havebeen used, tested or proposed for manufacture of lactic acid by

fermentation.

1.5. Source of carbohydrates for fermentation

Sucrose from cane and beet, glucose, and whey contain-

ing lactose, maltose and dextrose from hydrolyzed starch are

presently used commercially. Molasses and whey are gener-

ally low-priced sources of sugars for fermentation. Sulfite waste

liquor and Jerusalem artichokes are potential sources of lactic

acid.

Sugar (or dextrose) is the most pure source, but is very costly.Molasses and other wastes are cheap but contain large number

of impurities in larger quantities, which affect downstream pro-


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H.G. Joglekar et al. / Separation and Purification Technology 52 (2006) 117 3

cesses. Sugar cane juice can be a compromise between quality

and cost. Fermentation conditions also determine the quality of

broth and suitability of downstream processing options.

1.6. Fermentation

Carbohydrates are fermented to l-lactic acid by a number of

microorganisms. As lactic acid is formed and accumulated, pH

of the fermentor broth goes on lowering. This affects the produc-

tivity of microorganisms. Considerable research is being carried

out to develop strains, which canproduce lactic acid at lowerpH.

However it is still not a commercially viable preposition. In con-

ventional process pH of fermentor is continuously maintained

by addition of lime and thus converting lactic acid (partly) to

calcium lactate. Downstream processing of this broth includes

precipitation and acidification of calcium lactate to lactic acid.

This generates huge quantity of calcium sulphate, which poses

an environmental problem. Alternatively lactic acid can be con-tinuously removed from the fermentor by adsorption, extraction

or membrane separation. This is possible if fermentation is in

continuous mode. Alkalis other than calcium, such as ammo-

nium hydroxide, or sodium hydroxide (or carbonate) can also

be used. In that case alkalis need to be recovered and recycled

back.

1.7. Downstream processing

Conventionally two routes are followed: (i) the clarified fer-

mented liquor is concentrated to 32% well above crystallization

point and acidified with sulphuric acid to get the crude lactic

acid. (ii) The crude calcium salt which precipitates from the con-

centrated fermented liquor is crystallized, filtered, dissolved and

subsequently acidified with sulphuric acid according to process

described by Inskeep et al. [6] and Peckham [7]. In this route the

precipitated calcium lactate is separated from dissolved impu-

rities by filtration and washing. However, some impurities are

retained in the cake. There is a loss of calcium lactate along

with the washes. The conventional route generates huge quan-

tities of calcium sulphate cake. The cake with retained organic

impurities is difficult to dispose of.

Filtered fermented broth mainly contains impurities such as

residual sugar compounds, colour andother organic acids.These

impurities can be removed by reactive extraction, adsorption,electro dialysis and esterificationhydrolysis with distillation.

Research work done by various researchers on these purification

steps is reviewed and assessed here.

2. Reactive extraction

Lactic acid is poorly extractable by common organic solvent

due to their hydrophilic nature. Therefore, reactive extraction

has been considered for its recovery from aqueous solutions.

Reactive extraction of the lactic acid by a suitable extractant

has been found to be a promising alternative to the conventional

processes.Reactive extraction uses reaction between the extractant and

the material being extracted. The extractant in the organic phase

reacts with a material in aqueous phase and reaction complex is

solubilized into the organic phase. The lactic acid is recovered

from the organic layer by stripping. The prerequisite of an eco-

nomic recovery by extraction is a high distribution coefficient.

Reactive liquidliquid extraction has the advantage that lactic

acid can be removed easily from the fermentation broth (extrac-

tive fermentation), preventing the lowering of pH. Further, the

lactic acid can be re-extracted and the extractant and diluent

recycled to the fermentation process. However this implies that

extractant and diluent must not be toxic to the microorganism

used in fermentation. This can ideally be done for continuous

fermentation. Wasewar et al. [8], have reviewed and critically

analyzed the fermentation of glucose to lactic acid coupled with

reactive extraction.

Membrane extraction overcomes many drawbacks of the

extractive fermentation which have plagued us for long, and

offers other numerous advantages, such as (i) no fear of

back mixing, (ii) no direct exposure of microbes to extractionreagents, thereby ensuring biocompatibility, (iii) no need for

agitation, (iv) potentially high efficiency, etc. For the above rea-

sons, membrane extraction can be considered a very promising

alternative to the conventional solvent extraction for separation

and purification of lactic acid [9].

Huang et al. [10] and Tong et al. [11] successfully developed

an energy-efficient hollow-fiber membrane extraction process to

separate and recover lactic acid produced in fermentation.

2.1. Extractant

The extractant should have low water solubility, a high dis-tribution coefficient for the lactic acid and low distribution coef-

ficient for the impurities such as residual sugars [12].

The distribution coefficient is defined, as ratio of the concen-

tration of lactic acid in solvent phase to concentration of lactic

acid is aqueous phase. Organic bases or amine extractant can

provide much higher equilibrium distribution coefficient (Kd)

for the extraction of carboxylic acids than conventional solvents.

Kd =Cs

Cw, (1)

Cs is the total concentration of acid in solvent phase at equi-

librium, expressed as milliequivalent per milliliter; Cw the total

concentration of acid in water phase at equilibrium, expressedas milliequivalent per milliliter.

On account of its highly hydrophilic character, lactic acid

purification with solvent extraction by carbon bonded oxygen

donor extractants is not practical. Phosphorus-bonded, oxygen-

donor extractants contain a phosphoryl group which is a stronger

Lewis base than the carbon-bonded oxygen group. Further-

more, extractants belonging to this group coextract less water

and are less soluble in water than the extractants of the carbon-

bonded oxygen group.

It has been reported that long chain tertiary amines are suit-

able for the recovery of carboxylic acid from aqueous solution

[13]. Due to physical properties of aliphatic amines they mustalways be used in theform of solutionsin organic diluents.These

organic diluents affect the basicity of amines thereby, extraction


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behaviorof amineis significantly varied [14]. Recently, the influ-

ence of the chain length of tertiary amine on extractability has

been investigated in polar diluent and nonpolar diluent, respec-

tively [15]. In polar diluent such as 1-butanol, 1-hexanol, and

1-octanol, the extractability of tertiary amines increases with the

chain length of amines. However, the extractability of tertiary

amines decreases with the chain length of amines in nonpolar

diluent such as n-heptane [15].

Tertiary amines seem to be more suitable extractants for

organic acid removal compared to primary and secondary

amines [16].

2.2. Diluents

Long chain aliphatic amines are effective extractant for sep-

aration of carboxylic acid from dilute aqueous solution. Gen-

erally, the amine extractants are dissolved in diluent [17], an

organic solvent that dilutes the extractants to the desired concen-tration and controls the viscosity and density of solvent phase.

Solvents that contain functional group that interact strongly with

complex arecalled as theActive Diluent e.g. 1-octanoland that

of which interact inertly with complex are called Inert Diluent

e.g. n-hexane.

Diluents are classified as active diluents and inert diluents

depending on the interaction with the complex [18,19].

2.2.1. Choice of diluents

The choice of suitable diluents [20] for amine is not easy.

Polar diluents are more favorable than the nonpolar solvents

as shown in the extraction of lactic acid [12,18,21]. There areseveral important parameters, which must be taken into consid-

eration.

2.2.1.1. Distribution coefficient. The distribution coefficient

value in the extraction step should be greater than 1 at room

temperature and below 0.1 in the stripping step in order to obtain

a high concentration in the stripping raffinate.

2.2.1.2. Toxicity. Toxicity of the organic solvent and extractant

to microbes is the critical problem in extractive fermentation.

The degree of toxicity depends on the microbe and extractant

solution used [8]. Brink and Tramper [22] reported that theleast toxicity is expected from solvents of low polarity and high

molecular weight.

Toxic effect of extractants and diluents on microorganisms

can also be avoided by immobilization of cells. Yabannavar et

al. [23], reported that addition of soybean oil in immobilized

cells protects cells from toxic effects of extractants and diluents.

Tik et al. [24] obtained a maximum total lactic acid concen-

tration (2.5 times that without extraction) when 15% Alamine

336 in oleyl alcohol together with immobilized cell with 15%

sunflower oil was used.

Wasewar [8] concluded the Alamine 336 in oleyl alcohol,

which has the highest distribution coefficient, would serve as anideal extraction system unless the higher phase level toxicity of

octanol is reduced by using an immobilized enzyme system.

2.2.1.3. Solubility in water. This is important for several rea-

sons. One is economy and the diluents have to be recovered

from the raffinate phase by stripping. The physical properties

of fermentation broth make it desirable to avoid raffinate strip-

ping. A low concentration of some cheap hydrocarbon can be

acceptable for this consideration.

2.2.1.4. Viscosities and density. Low viscosity and low density

promote phase separation. These properties are best achieved

with paraffinic hydrocarbons.

2.2.1.5. Stability. Hydrocarbons are preferable to alcohol and

halogenated hydrocarbons as they are more stable.

2.3. Effect of extractants, diluents and pH on distribution

coefficient

Table 1 summarizes the reported results for various extractantin diluents and the Kd values. In general, the extraction power of

extractant is dictated by the basicity of the amine. The diluents

also affect the basicity of the amine and thus the stability of the

ion pair formed and its solvation power.

The use of tertiary amines including tri-n-octylamine (TOA),

triisooctylamine, and Alamine 336 for the extraction of

lactic acid from aqueous streams has been often reported

[12,1719,21,2527]. Tertiary amine extractants are effective,

with Kd strongly dependent upon the nature of the diluent [13].

The lactic acid extracted had to be stripped for the final

production of lactic acid. The reaction of amine and acid is

exothermic reaction, so the extraction efficiency of lactic acid

decreases with increasing temperature for active diluents where

as it shows little effect for inert diluents [16,18,19,27,28]. The

stripping efficiency does not change with the variation of inac-

tive diluent except for polar chlorobenzene [19,29].

The pH of the aqueous phase is an important parameter for

the reactive extraction of organic acids. Yang et al. [30], reported

that lower pH values result in good separation of lactic acid by

long chain tertiary amines. In the intermediate pH range (35),

Kd decreased with increasing equilibrium pH of the aqueous

phase. However, in the extremely high and low pH ranges, Kdremained insensitive to pH values. Similarly, Choudhury et al.

[32], reported that the distribution coefficient of lactic acid was

high at pH 2.0. In addition, these authors pointed out that theamount of amine in diluents affects the reactive extraction of

organic acids. Kd increased with increasing amount of aliquat

336, in their studies. They reported that increasing amine con-

centration might have a toxic effect on microorganisms in the in

situ extractive fermentation.

Temperature and initial organic acid concentration are also

important parameters for the extraction of organic acids. Yaban-

navar and Wang [33] investigatedthe extraction of aqueous lactic

acid by trioctylphosphineoxide in dodecane and Alamine 336

in oleyl alcohol. In their study, Kd decreased with increasing

initial lactic acid concentration and increased with increasing

concentration of Alamine 336 in oleyl alcohol. Martin et al.[21] studied the extraction of lactic acid from aqueous solu-

tions by Alamine 336 dissolved in toluene. They observed


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Table 1

Kd values reported in literature

Serial number Initial concentration Extractant Diluent Kd Reference

1 20% w/w TOAtripropylamine (TPA) (2:8w/w) 1 mol/kg 1-Octanol/ n-heptane

(3:7 w/w)

0.8 [15]

10% w/w TOATPA (2:8 w/w) 1 mol/kg 1.2

7.5% w/w TOATPA (2:8 w/w) 1 mol/kg 4

5% w/w TOATPA (2:8 w/w) 1 mol/kg 90

2 20% L.A. Tri-n-butyl phosphate (TBP) 0.95 [34]

TOA (0.8 M) Chloroform 9.44

TOA (0.8 M) Tributyl phosphate 7.42

Tributyl amine (TBA) Methylisobutylketone

(MIBK)

0.21

TOAmethylene chloride (0.6 M) Hexane 2.52

Chlorobenzene 0.2

Heptane 2.14

3 Model media

containing 90% l+

lactic acid

Cynex 923 (0.85 mol/l) Kerosene 2 [35]

Hostarex-327 (60% w/v) Xylene 4.44

Trioctylphosphine oxide (TOPO) Xylene 2.2

4 L.A. (2.3mol/l) TOA (1 M) Chlorobutane 1.4 [36]

L.A (2.6 mol/l) TOA (1.2 M) Methylene

chloriden-hexane

1.45

5 1.3 mol/l L.A. MIBK 0.13 [17]

Alamine 336 (0.3 mol/l) MIBK 8.3

Alamine 336 (0.3 mol/l) Chloroform 5.3

Trilauryl amine (1 mol/l) Xylene 8.3

6 0.0051.5 mol/l Alamine 336 940% MIBK decanol,

octanol

4.24 [37]

24.0

26.0

7 10 g/l L.A. 50% Alamine 336 Oleyl alcohol 13 [38]100 g/l L.A. 50% Alamine 336 Oleyl alcohol 4

8 1.6 mol/l L.A. Alamine 336 (40% v/v) MIBK 4.24 [39]

9 Calcium lactate Alamine (48%v/v) Octanol (30% v/v)

Isopar K Exxon

(22%) CO2 (300psig)

0.62 [40]

10 79 g/l lactate TOPO (30 wt.%) MIBK (70 wt.%) 1.05 [41]

Alamine 336 (82 wt.%) 10% Octanol 8%

isopar K

3.35

Alamine (100%) 0.36/5.9

Alamine 336 (89 wt.%) 9% Dodecanol 2%

isopar K

2.6

that the extraction of lactic acid decreased with increasing

temperature.

2.4. Third phase formation

In extraction of lactic acid with long chain tertiary amines

dissolved in organic diluents a third phase may form between

aqueous and organic phase. This phase is not broken by cen-

trifugation at high rpm. The third phase represents limiting

conditions for extraction, which must be avoided [42]. For best

separation of the emulsion that results from the third phase, a

phase modifier is being added to the organic solvent, represent-ing a long chain aliphatic alcohol, a component assuring a higher

solubility of the acid complex in the extract phase. Sometimes

mixed tertiary amine of short chain amine and long chain can

overcome the third phase formation. No cloudy, bubbly looking

phase was observed in this study. The prevention of third phase

makes the phase separation easy, thereby, the settling time gets

shortened.

2.5. Complex formation

Long-chain aliphatic amines are effective extractants for the

separation of carboxylic acids from dilute aqueous solution. The

specific chemical interactions between the amines and the acid

molecules to form acidamine complexesin the extractant phaseallow more acid to be extracted from the aqueous phase. Gen-

erally, the amine extractants are dissolved in a diluent such as


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a ketone, an alcohol, chloroform, etc., that is, an organic sol-

vent that dilutes the extractant to the desired concentration and

controls the viscosity and density of the solvent phase.

Many factors have been found to influence the equilibrium

extraction characteristicsof these systems. Three important vari-

ables are the nature of the acid extracted, the concentration of

the extractant, and the type of diluent. These factors have been

extensively studied for the extractions by tertiary amines of sev-

eral carboxylic acids, including lactic acid [31,43].

Eyal et al. [44], summarized the extraction of acid by amines

and proposed thatfour majormechanisms determine acid extrac-

tion by amine-based extractants: anion exchange, ion-pair for-

mation, H-bond formation, and solvation. These four mecha-

nisms depend on the strength of the amine-based extractant. For

amines of basicity similar to or higher than that of the anion

of the extracted acid, extraction is governed by ion-pair forma-

tion. H-bonding of undissociated acid becomes important only

for extractions of weak bases. Also, the specific basicity of theextractant (pKa,B), defined as follows, is suggested to express

the nature of extractant

R3NH+Ka,BR3N+H

+, (2)

Ka,B =[R3N][H

+]

[R3NH+]

, (3)

where R3N represents TOA. The species in the organic phase

are marked with an overbar, and all of the concentrations are

expressed in molar terms. pKa,B

depends on the amine concen-

tration and diluent type, representing the structure of the amine,

multiplied by coefficients for diluent solvation properties and

the properties of the anion of the extracted acid (hydrophobic

properties and steric hindrance).

The reactive extraction equilibrium for polar dilute solu-

tions of organic solutes can be described by the mass action

law in which the equilibrium behavior is modeled by postulat-

ing the formation of various stoichiometric complexes of acid

and amine. In addition, it is assumed that the carboxylic acid

is dissociated in water and extracted into the extractant phase

through the physical solubility of the solute in the diluent of

the extractant phase and the formation of 1:1, 2:1, 3:1, and

1:2 acidamine complexes, where the 2:1 and 3:1 complexesresult from the dimer and trimer, respectively, of the acid in the

extractant phase and the 1:2 complex results from hydrogen-

bond association between TOA and the hydroxyl and aldehyde

group on carboxylic acid. The physical extraction with diluent

and reactive extraction with TOA fit the simple additive model.

Although the stoichiometry of lactic acidamine extraction

systems has been studied there is no general agreement. The

formation of (1:1) acidamine complex has been commonly

suggested. Prochazka et al. [45] have indicated the forma-

tion of (1:1), (2:1) and (2:2) complexes for the extraction

of lactic acid by trialkylamine in mixtures of 1-octanol-n-

hexane. The quantitative description of the effect of amine andacid concentration on the change in complex composition is

unclear.

2.6. Re-extraction

In reactive extraction, the amine extractant recovers the acid

by reacting with it to form an acidamine complex that is sol-

ubilized into the extractant phase. A Second step, referred to

as regeneration, reverses this reaction to recover the acid into a

product phase and the acid free extractant, available for recycle.

The reported regeneration methods for lactic acid from a

loaded organic phase are described individually in the following:

Tamada and King [17] considered two approaches for regen-

eration through backextraction into an aqueous phase. These

involve changes in the equilibrium relationship through a swing

of temperature and a swing of diluent composition. Yabannavar

and Wang [23,33] suggested two methods for recovery of lactic

acid from a loaded solvent phase: using NaOH and using HCl.

2.6.1. Using NaOH

In the first recovery method, Yabannavar and Wang [23] sug-gested the backextraction of lactic acid from a loaded organic

phase (lactic acid + Alamine 336 + oleyl alcohol) with small vol-

ume of a sodium hydroxide solution [1:10 (v/v) NaOH-solvent].

NaOH in excess of stoichiometric amounts can be used to

ensure complete lactic acid recovery. Yabannavar and Wang [23]

obtained 100% recovery of lactate. The resultant high product

concentration is certainly desirable from the point of economic

product recovery.

However, the acid is then recovered as sodium lactate. One

must add an appropriate acid (e.g., sulfuric acid) to return it to

the free acid form. This approach has the same drawbacks as the

classical calcium precipitation process for direct recovery from

the aqueous feed. Both sulfuric acid and NaOH are consumed,

and a waste salt is formed, which requires disposal. The degree

of reextraction of lactate with 0.1 N NaOH is high (90%). The

degree of reextraction with water amounts to only 55%.

2.6.2. Using HCl

In the another recovery method suggested by Yabannavar and

Wang [33], concentrated HCl is used to essentially displace the

lactic acid from the loaded organic phase (lactic acid + Alamine

336 + oleyl alcohol). More than stoichiometric amounts of HCl

were necessary to recover most of the product from the solvent.

The lactic acid recovered through backextraction with HCl is in

the undissociated form. It is possible to regenerate the solvent bydistilling diluent in thedispersed organic phase. This methodhas

the drawbacks that aqueous HCl is highly corrosive and requires

special material of construction (glass lined/graphite).

Yabannavar and Wang [33], recommended the reextraction

of the free acid from Alamine 336/oleyl alcohol solution with

cone. HCI. The obtained yield was fairly high (83%), however,

the emulsion formed during the reextraction was very stable.

2.6.3. Temperature-swing regeneration

In a temperature-swing extraction/regeneration scheme [46],

the extraction is carried out at relatively low temperature, pro-

ducing an acid-loaded organic extract and an aqueous raffinatewaste stream containing the unwanted feed components. Dur-

ing regeneration, the extract is contacted with a fresh aqueous


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stream at a higher temperature to produce an acid-laden aqueous

product stream and an acid-free organic phase. The concentra-

tion of the acid achievable in this stream depends on the amount

of change in the extraction equilibrium between temperatures

and can be higher than that in the original aqueous feed stream

[46].

At low acid concentrations, a strong diluent effect can be

recognized. The Kd value is a function of the polarity of the

diluent and its ability to form hydrogen bonds. At higher acid

concentrations, however, this diluent effect diminishes consid-

erably. For highly complexed amines, the Kd value depends only

slightly on the acid concentration. The Kd value is considerably

reduced with increasingtemperature. This behavior ofKd is used

to reextract the citric acid into the aqueous phase by temperature

increase. Because of the lower enthalpy change, the extraction

efficiency of lactic acid by temperature-swing regeneration is

low [47].

2.6.4. Using trimethyl amine (TMA)

Lactic acid extracted in the organic phase can be back

extracted with a stronger volatile amine like TMA in aqueous

phase. It avoids consumption of chemicals and creation of salt

byproduct. The aqueous base, which is volatile, enables thermal

decomposition of the acidbase complex in the aqueous back-

extract. The decomposition forms lactic acid as a product and

freebase as a vapor that can be reabsorbed in water and recycled

for reuse in backextraction. The most obvious water-soluble,

volatile base is ammonia. However, ammonia and both primary

and secondary aminesform amides when they are heated in mix-

tures with carboxylic acids [4850]. The amides are sufficiently

stable so that it is difficult to reverse the process and recover the

amine.

The theory of extraction accompanied by chemical reaction

has been used to obtain the kinetics of back extraction of lactic

acid by aqueous TMA. In thermal regeneration of TMA, 99%

of TMA was removed at 200 mmHg from trimethylammonium

lactate aqueous solution.

An approach for regeneration and product recovery from

organic extracts (alamine, TPATOA in diluents) is to back

extract lactic acid with a water soluble, volatile tertiary

amine such as trimethyl amine. Equilibrium data presented by

researchers shows near stoichiometric recovery of lactic acid

from amine extract.The organic phase, which is recycled to the fermentor, may

contain residual dissolvedTMA,whichcan affect the bioactivity

of the enzyme.

2.6.5. Diluent swing

This is based on a shift of the equilibrium distribution of acid

from the aqueous phase to the organic phase between forward

and back extraction caused by a change in composition of the

diluent with which the extractant is mixed. This diluent compo-

sition swing facilitates back extraction of acid into an aqueous

product phase. The composition of the acid laden organic phase

leaving the extractor is altered, by either removal of the diluentor addition of another diluent, to produce a solvent system that

promotes distribution of the acid to the aqueous phase.

This altered organic phase is contacted with a fresh aque-

ous stream in the regenerator to produce the acid laden aqueous

product andthe acid-freesolvent for recycle to theextractor [47].

Adjustment of the diluent composition can also occur before

this solvent reenters the extractor. This approach involving more

than one diluent appears to be more complicated than the TMA

approach, where an easily removable volatile amine (TMA) is

the only externally introduced component. This process has the

disadvantage of diluting the extract stream and requiring dis-

tillation of large amounts of solvent (after the regeneration) to

obtain the same shift in the active/inert diluent ratio.

Tamada and King [47], suggested the diluent-swing regen-

eration process for lactic acid. Baniel et al. [40], also described

regeneration by back extraction following a changein thediluent

composition. In the diluent-swing process, extraction is carried

out in a solvent composed of the amine and a diluent that pro-

motes distribution of the acid in the organic phase.

To date, diluent systems have been composed of organic sol-vents that are liquids at room temperature. A drawback of such

systems is that changes in extractant-phase composition gen-

erally involve a distillation step to separate the active and inert

diluents.To avoid this energyexpense, a new process is proposed

that will replace the inert liquid diluent with a gas anti solvent.

Here, anti solvent is used to connote a substance that has a low

capacity to solubilize the extracted acid. In this process, the dilu-

ent composition change will be effected by pressurizing it with

a gaseous antisolvent (e.g., propane).

For carboxylic acids that exist as solids at room temperature,

this composition change might induce precipitation of the acid

product from the extractant phase. Alternatively, for acids that

are not solids at room temperature, this composition change will

be carried out while the extractant is in contact with an aqueous

product phase. Here, the antisolvent will shift the equilibrium

distribution of the acid to favor the aqueous product phase.

The idea for this process stems from previous work [51] on

extraction of carboxylic acids with amine extractants that indi-

cated that the chain length of liquid-phase aliphatic hydrocarbon

diluents (C7C12) has little effect on extractant loading. This

result is not surprising, since such diluents provide essentially no

stabilization of the acidamine complex. It is therefore expected

that gaseous aliphatic hydrocarbons (e.g., propane) will behave

similarly as inert diluents. Acid extraction power is expected

to decrease with increasing concentrations (i.e., higher partialpressures) of propane in the organic extractant phase. Thus,

a diluent-swing regeneration process will be devised whereby

pressurizing the system with propane gas will effect changes in

extractant composition. A benefit of this process over conven-

tional recovery techniques is that the diluent components can be

easily separated (e.g., by a flash operation) without involving a

distillation step.

2.7. Choice of extraction

The main parameters for selection of a diluent-extractant

system for extraction of lactic acid are distribution coefficient,toxicity, complexation constant and feasibility for back extrac-

tion. From the literature it is noted that Alamine 336 in proper


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diluent is the best single extractant in terms of distribution coef-

ficient, toxicity and feasibility for back extraction. The oleyl

alcohol is a better diluent than octanol. However this system

forms a third layer, which is undesirable.

In reactive extraction by using mixed diluents such as 1-

octanol/n-heptane, the third layer formation is avoided, as well

as optimum extractability can be obtained by proper ratio of

short chain amine and long chain amine. Extraction efficiency

increases with decreasing initial lactic acid concentration in

aqueous phase. For 5 wt.% lactic acid concentration, the maxi-

mum extraction efficiency was obtained for TPA/TOA ratio in

the range of 6:48:2.

Regeneration of lactic acid-laden amine extractants by addi-

tion of a gas antisolvent appears to have advantages over more

traditional diluent swing or temperature swing methods. A

potential secondary benefit of regeneration by gas antisolvents

might be the ability to fractionate a mixture of carboxylic acids.

However this needs to be evaluated.Thus the best results can be obtained by employing reactive

extraction using a mixture of TPA and TOA as extractant, 1-

octanol and n-heptane as diluent and gas-antisolvent-induced

regeneration for reextraction. It is to be used advantageously

with continuous or semi continuous fermentation. Reactive

extraction does not totally separate other organic acids from

lactic acid and further purification is necessary.

3. Adsorption

Recovery of carboxylic acids from fermentation broths

presents a challenging separation problem, because of the dilute,

complex natureof fermentation broths. Methods of recovery that

utilize separatingagents, such as solidsorbents, that are selective

for carboxylic acids are attractive and reported by researchers

such as King [52], Tung and King [53]. Important characteristics

of extractants and solid sorbents are a high capacity for the acid,

a high selectivity for the acid as opposed to water and substrate

(e.g., glucose), regenerability, and, depending upon the process

configuration, the biocompatibility with microorganisms. Many

fermentations, such as that for lactic acid production, are subject

to end-product inhibition [23,54]. If a solid sorbent can be used

in situ or in an external recycle loop, higher overall yields can

be achieved.

3.1. Reported research

Many fermentations to produce carboxylicacids operate most

effectively at pH abovepKa of theacid product. Forexample, lac-

tic acid (pKa = 3.86) is typicallyproducedat pH 56[55,56].One

approach for recovering carboxylic acids from such solutions

is to use agents that are sufficiently basic to retain a substan-

tial capacity several pH units above the pKa of the carboxylic

acid. Tung and King [53] investigated extraction and sorption

of lactic and succinic acids using different basic extractants and

polymeric sorbents. The results showed that the uptake in the

pH range 56 varied substantially from one agent to another andwas strongly dependent upon the basicity and capacity of the

agent. Agents to be used in fermentation processes should pro-

vide high selectivity between the product carboxylic acid and

substrate sugars. In addition to conservation of substrate, one

reason why very high selectivitys are often sought is the ten-

dency for small amounts of sugars in a product such as lactic

acid to cause discoloration. Reported measurements of uptake

capacities for sugars and for selectivity achieved between car-

boxylic acids and sugars with extractants and/or solid sorbents

are few and fragmentary.

Kaufman et al. [57], screened a series of solid sorbents

preliminarily for possible utilization in biparticle fluidized-bed

fermentation to produce lactic acid from immobilized Lacto-

bacillus delbreuckii, measuring selectivity between acid and

sugar as well as other properties. Kaufman et al. [58], presented

selectivities between lactic acid and glucose obtained with a

fixed bed of the sorbent Amberlite IRA-35 under a particu-

lar set of operating conditions. Evangelista et al. [59], reported

breakthrough curves for lactic acid and glucose during fixed-bed

adsorption with actual fermentation broths.For typical lactic acid fermentations, the sorbent should

demonstrate substantial uptake in the pH 56 range [53,60].

Ion exchange technique is widely used in bio-separation

[61,62] and several different ion exchangers such as poly(4-

vinylpyridine) resin (PVP) [63], IRA-420 [64], IRA-400 [65,66]

have been studied on the recovery of lactic acid in the past

few years. However, little systematic research has been done

on the effect of different operating conditions on the separa-

tion efficiency of lactic acid and especially on the purification

performances of lactic acid.

Karl-Heinz et al. [67], discloses the separation of lactic acid

from a fermentation medium with an adsorbent comprising a

polymer with tertiary amino groups as described in US Patent

4,552,905 [68].

Kawabata et al. [69], separated carboxylic acid by using a

polymer adsorbent of pyridine skeletal structure and a cross-

linked structure.The polymer adsorbentshowed goodselectivity

and high adsorption capacity for carboxylic acids even in the

presence of inorganic salts. The selected eluants were aliphatic

alcohol, aliphatic ketone, and carboxylic ester.

Evangelista and Nikolov [70], recovered lactic acid from

fermentation broth by weak base polymer adsorbents MWA-

1, IRA-35, and VI-15. The pH for the adsorption of lactic acid

was below its pKa and fermentation broth was acidified by using

cation exchange resin instead of using inorganic acid to elim-inate possible competition between inorganic acid and lactate

in the subsequent adsorption steps. Methanol and 5% NH4OH

were used as elutants. Though 1.5 times of bed volume of 5%

NH4OH could recover all the adsorbed lactic acid from MWA-1

column, product purity was not high. However, 6.8 times of bed

volume of methanol could completely desorb lactic acid from

VI to 15 anion exchange resin with higher purity.

Simulated moving bed (SMB) chromatography is a continu-

ous separation process that has many important industrial appli-

cations [71]. An SMB consists of a circle of chromatographic

columns. The circle is typically divided into four zones by two

inlet ports and two outlet ports. The four ports move periodicallyby one column length along the mobile phase flow direction to

follow themigrating solute bands.The port movement maintains


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product purity and yield, while achieving simulated counter-

current movement between the adsorbent and the fluid [72].

In comparison to batch chromatography, SMB processes have

higher yield and product purity as well as lower solvent con-

sumption. SMB has been used, for instance, for hydrocarbon

and high fructose corn syrup purification [71]. Recently, SMB

has been developed for the separation of racemic mixtures or

isomers [73,74].

Lee et al. [75], explored the feasibility of developing a SMB

process for the separation of lactic acid from other organic

acids present in a fermentation broth. Poly(4-vinylpyridine)

resin (PVP), which was found to have a high capacity and selec-

tivity for organic acids in a previous study [76], was chosen as

the adsorbent. A systematic design method, which is based on

the standing wave analysis for Langmuir isotherm systems, was

tested for this separation [74]. Adsorption isotherms and mass

transfer parameters for the two organic acids were determined

from frontal chromatograms. These parameters were first vali-dated by comparing the single-column frontal chromatograms

with simulations based on a rate model [77]. The validated

parameters were applied in the standing wave design to find the

four zone flow rates and step time for a laboratory SMB unit.

High product purity (99.9%) and relatively high yield (>93%)

were achieved in the SMB experiments. SMB column profiles

and effluent histories can be better explained if the adsorption

isotherm of lactic acid is represented by a modified Lang-

muir equation. The standing wave design method was extended

to nonlinear systems with modified Langmuir isotherms. Rate

model simulations show that this method can achieve higher

purity and higher yield for this separation than the design based

on the Langmuir isotherms.

Chen et al. [78], examined polyvinyl pyridine (PVP) and

activated carbon for the adsorption characteristics pertinent to

their application in lactic acid fermentation. For PVP the lin-

ear adsorption constant, Kad, was between 0.7 and 1.0 for an

equilibrium pH range of 39. The pH was adjusted by acid/base

addition,similar to pH control in fermentation. Thevalues ofKadin the pH-adjusted systems were much lower than that reported

for pure lactic acid solutions, i.e., about 9.7. Furthermore, no

clear effect of pH was observed. These are attributed mainly to

the competition of anions (Cland lactate) for the adsorption

sites of protonated pyridinal N. Its adsorption capacity was also

found to decrease with the base regeneration (by about 14%

each time) after being contacted with the culture broth. These

factors limit its potential application in lactic acid fermentation.

Activated carbon was much more effective in lactic acid/lactate

adsorption than PVP. The adsorption further favored lower pH

under acid (HCI) addition. Activated carbon has been reported

to adsorb glucose. However, the presence of glucose in 070 g/l

was found in this study to have an insignificant effect on lac-

tate adsorption. Cells ofL. delbrueckii also adsorbed rapidly on

activated carbon. This cell adsorption had a negative effect on

lactate adsorption.

Kulprathipanja et al. [79], studied the separation of lactic acid

from a fermentation broth by using an adsorbent comprising

a water-insoluble macro-reticular gel or weakly basic anionic-

exchange resin possessing tertiary amine or pyridine functional

groups or a strongly basic anionic exchange resin possessing

quaternary functional groups. The resins are in sulphate form

and have a cross-linked acrylic or styrene resin matrix. Theadsorption mechanism is shown Fig. 1. For tertiary amine and

pyridine-function-containing ion exchange resins, the lone elec-

tron pair of the nitrogen atom enables nitrogen atom to form

hydrogen bond with sulfate ion. IRA-400, strongly basic qua-

ternary ammonium ion exchange resin has positive charge and

can form ionic bond with sulfate ion. The sulfate form of qua-

ternary ammonium of anion exchange resin has a weakly basic

property and can adsorb lactic acid through acidbase interac-

tion. Consequently, the adsorption of lactic acid is not affected

by inorganic salt in fermentation broth. Lactic acid is desorbed

with water or dilute inorganic acid. The pH of the feed is main-

tained below the ionization constant (pKa

) of the lactic acid to

obtain high selectivity.

Several different ion exchangers such as IRA-400, PVP,

and IRA-92, Amberlite were tested. IRA-92, a weakly basic

exchanger, is selected as the ion exchanger for the purification

of lactic acid because of its fair purity and recovery yield of

lactic acid comparable with other resins results.

Tong et al. [80], examined the capacity of IRA-92 to lactic

acid in the fermentation broth, and then, optimized the operating

conditions, and finally gained a fair product of lactic acid with a

higher purity, recovery yield and productivity with only one-step

chromatographic procedure from the supernatant of the fermen-

tation broth. The experimental results demonstrate that when the

Fig. 1. The mechanism of adsorption of lactic acid on the anion exchange resin.


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pH of the fermentation broth is 6.0, the recovery yield, purity

and productivity in the lactic acid purification are the highest.

With the decrease of the sample volume loaded and of flow rate,

the recovery yield and the purity are improved but the productiv-

ity apparently reduced. In the experimental scale, the scale-up

of purification process exhibits little influence on the recovery

yield and the purity. Under the preliminary optimal conditions,

the yield, purity and specific productivity are 82.6%, 96.2% and

1.16 g LA/(g-resin day), respectively.

Raya-Tonetti et al. [81], studied the use of strong anionic

exchange resin (IRA-400) to recover lactic acid directly from

fermentation in an upflow fluidized bed column, resulting in

0.18 g lactic acid/g resin bound with a subsequent elution of

94%. When the culture broth was heated and adjusted pH to 8.0,

0.4 g lactic acid was bound per gram of resin, with a subsequent

elution of 90%. l (+) and d () lactic acid isomers distribution

was analyzed in the elution product resulting in an increase of

l (+) isomer concentration. The resin did not alter its bindingcapacity even after 23 cycles. The lactic acid recovery attained

was not dependent on the increase of the resin poured to the

columns but due to the increase in the hydraulic residence time

and back mixing which resulted in a high contact time between

lactate ions and resin particles.

Srivastava et al. [64], separated lactic acid by using IRA-

400 column coupled with fermentor. This study was focused on

improving fermentation yield, and the separation performance

of IRA-400 was not studied. The Amberlite IRA-400 resin has

proper pore size and high adsorption capacity for recovery of

lactic acid and it can adsorb lactic acid in wide pH range.

Cao, et al. [65], studied the application of Amberlite IRA-

400 anion exchange resin for the recovery ofl-(+)-lactic acid

from fermentation broth. Adsorption isotherm and breakthrough

curves for the separation of (l+)-lactic acid were obtained at pH

5.0 and 2.0, respectively. Recovery experiment coupled with

fermentor was carried out successfully by using a column with-

out autoclaving. Different types of adsorption isotherms were

found at pH above and below the pKa (3.86) of lactic acid. The

isotherm was found to be a Langmuir type at pH 5.0, whereas the

isotherm was type II (multilayer adsorption) at pH 2.0. At pH 5.0,

the maximum adsorption capacity of the resin, and dissociation

constant, were 222.46 mg/g wet resin and 60.7 mg/ml, respec-

tively. Breakthrough curve for the separation of lactic acid from

fermentation broth was also obtained. The maximum adsorptioncapacity (197.09 mg/g wet resin) at pH 5.0 was much higher

than that at pH 2.0 (106 mg/g wet resin). Proper elution and

washing conditions were sought by using H2SO4, methanol,

ammonia or their mixtures as eluant. When column separa-

tion was performed at pH 5.0 by using 50% (v/v) methanol

as washing solvent and 1.0 M H2SO4 as eluant, the total yield

was 86.21%. However, the total yield was 92.11% when the col-

umn separation was performed at pH 2.0 and water was used as

eluant.

IRA-400 was successfully applied for the separation of (l+)-

lactic acid from fermentation broth at pH above and below the

pKa (3.86). It shows different adsorption mechanisms in the sep-aration of lactic acid at pH above and below pKa. 1.0 M H2SO4could be used for the elution of lactic acid at pH 5.0 with high

recovery. Product loss in column washing step could be reduced

using methanol. The process is simple and feasible in lactic acid

industry and could be coupled with fermentation.

Salts ions in fermentation broth and inorganic acids used for

adjustment of pH did not affect the adsorption performance of

resin for lactic acid at pH 2.0. The elution of the IRA-400 anion

exchange resin could be easily performed using water as eluant.

Ionic exchange resins have been utilized by Vaccari, et al.

[82], Senthuran et al. [83] and Kaufman [84], obtaining 0.1, 0.18

and 0.2 g lactic acid/g resin, respectively. All purification tech-

niques mentioned earlier, need prior cell removal by filtration

or by centrifugation. Those steps mean increase in equipment

and energy costs, increase in total process time, and reduction

in total yield.

Lactic acid was recovered and purified by using a fluidized

bed column refilled with a strong anionic exchange resin:

Amberlite IRA-400 achieving 0.126 g LA/g resin [85]. This

methodology is more useful considering the fact that only con-trolling the ascensional velocity is sufficient to washout the

biological solids and to bind the lactate to the resin in only

one step. A very important advantage that this technique counts

with is the use of simple equipment, such as a glass column,

an anionic exchange resin, a peristaltic pump, and commercial

grade reagents, to carry out the early recovery process of lactic

acid from the culture [86].

Sosa, et al. [87], studied the influence of two design parame-

ters, bed-diameter (D) and bed-height (H), on lactic acid binding

capacity utilizing fluidized bed columns refilled with anionic

exchange resin. The binding capacity of the resin was constant

during the lactic acid downstream process when the columns

were scaled-up on diameter, keeping constant the bed height.

Substantial increase (50%) in lactic acid adsorption to Amberlite

IRA-400 was achieved in the case of scaling up the H parameter

maintaining the diameter of the columns constant.

The same ratio of grams of lactic acid to grams of resin was

fed to both columns in all experiments. Thus, the lactic acid

recovery attained was not dependent on the increase of the resin

poured to the columns but due to the increase in the hydraulic

residence time and back mixing which resulted in a high contact

time between lactate ions and resin particles. By changing the

settled bed height from 2.5 to 5cm for each diameter of column

analyzed, it was possible to obtain 50% increase in the binding

capacity of the resin in all experiments. This fact was attributedto a higher contact time between theculture broth andthe anionic

resin produced by the increase in back mixing and lactic acid

residence time.

There is a further need to study the effect of other parameters

on the performance of lactic acid purification process utilizing

fluidized bed columns, taking into account the developing of this

procedure on larger scale.

The uptake data for lactic acid with all three sorbents (Dowex

MWA-1, Reillex 425, Amberlite IRA-35) are well described by

1:1 complexation [88], which gives a functional form equivalent

to the Langmuir equation.

Qca

Qm=

KCa,f

(1+KCa,f), (4)


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where Qca is thecomposite uptake of lacticacid (g of lacticacid/g

of sorbent); Qm the maximum value of sorbed lactic acid at high

concentration (g of lactic acid/g of sorbent); Ca,f the weight

fraction of lactic acid in the final solution; K the complexation

constant for sorption (g of resin/g of lactic acid).

Daietal. [89], has found that the uptakeof lacticacidfor sorp-

tion by Dowex MWA-1 is much higher than that for extraction

by Alamine 336. This advantage is more significant in the higher

pH range. On the other hand, the uptake capacity for water is

much higher for sorption than for extraction, and this results in a

substantially higher uptake of glucose onto the sorbent. Marked

swelling of the sorbent in the solution reduces the selectivities

for acid over water and glucose.

Sun et al. [90] demonstrated that the in situ product removal

process using the OH-form anion-exchange resin can be suc-

cessfully carried out for lactic acid fermentation. Both in the

shaking flasks and in the airlift bioreactor (ALB), the broth pH

was controlled at values higher than 6, and over 90% of the lacticacid produced by the bioconversion was recovered by the anion

exchanger. In addition, the mathematical model developed for

the in situ product removal (ISPR) process agreed well with the

experimental results.

3.2. Choice of adsorption

Adsorption or theion exchangeis a reliable technology. How-

ever, the process requires regeneration of an ion exchange resin

and adjustment of the feed pH to increase the sorption efficiency,

requiring large amounts of chemicals and needs to treat and dis-

pose of large quantities of salts/effluents.

Adsorption on ion exchange resin has the advantage that it

can be coupled with fermentation process. For lactic acid fer-

mentations, the sorbent should demonstrate substantial uptake

in the pH range of 56.

The uptake of lactic acid for sorption by Dowex MWA-

1 is much higher than that for extraction by Alamine 336.

This advantage is more significant in the higher pH range.

The capacity of IRA-92 to sorb lactic acid in the fermenta-

tion broth, at optimized operation conditions, is high with a

higher purity and recovery yield with only one-step chromato-

graphic procedure from the supernatant of the fermentation

broth.

The isotherm was found to be a Langmuir type at pH 5.0,whereas the isotherm was type II (multilayer adsorption) at pH

2.0. At pH 5.0, the maximum adsorption capacity of the resin,

qm and dissociation constant, Kd were 222.46 mg/g wet resin

and 60.7 mg/ml, respectively for recovery of l (+)-lactic acid

from fermentation broth using Amberlite IRA-400. The maxi-

mum adsorption capacity (197.09mg/g wet resin) at pH 5.0 was

much higher than that at pH 2.0 (106 mg/g wet resin). Proper

elution and washing conditions were sought by using H2SO4,

methanol, ammonia or their mixtures as eluant. When column

separation was performedat pH 5.0by using 50%(v/v) methanol

as washing solvent and 1.0 M H2SO4 as eluant, the total yield

was 86.21%. However, the total yield was 92.11% when the col-umn separation was performed at pH 2.0 and water was used as

eluant.

The Amberlite IRA-400 resin has proper pore size and high

adsorption capacity for recovery of lactic acid and it can adsorb

lactic acid in wide pH range.

To recover lactic acid from fermentation broth the most suit-

able adsorbent is found to be Amberlite IRA-400 resin with

methanol and 1.0 M H2SO4 as eluant. It has high adsorption

capacity to adsorb lactic acid in wide pH range. The elution

by methanol and 1.0 M H2SO4 is also advantageous to directly

esterify the recovered lactic acid in methanol. Thereby avoiding

the addition of alcohol and acid catalyst during esterification

to purify the lactic acid. Further purification by esterification

is necessary after adsorption, as it does not remove all other

organic acids.

4. Electrodialysis

Electrodialysis is one of very promising and perspective

methods provided by rapid development of the membrane pro-cesses, especially the membranes in the 80s and 90s [91].

Electrodialysis fermentation EDF is also studied by several

authors [9295]. Electrodialysis fermentation (EDF) is promis-

ing because it can remove product lactic acid continuously from

the fermentation and maintain the pH of the broth.

Most of the literature [9599], shows the feasible produc-

tion of lactic acid from lactate salts in two steps: conven-

tional electrodialysis (ED) for concentration and purification

and bipolar electrodialysis for conversion of lactate salts into

lactic acids with recovery of alkali. Bipolar membrane elec-

trodialysis also referred to as water splitting electrodialysis,

can convert aqueous salt solutions into acids. A water split-

ting stack is similar to a conventional (mono-polar) electro-

dialysis stack but incorporates a third type of membrane, the

bi-polar membrane, which is composed of a cation and anion

membrane layers laminated together. To meet the feed require-

ments of EDBM, clarification of the fermentation broth is first

performed by microfiltration. After the conversion of sodium

lactate into lactic acid, the product is purified by ion exchange

resins.


Hongo et al. [91], proposed to use electrodialysis for in

situ lactate recovery to reduce the product inhibition. The mainobservation was fouling of anion exchange membranes by cells

in the electrodialysis fermentation(EDF). To solve this problem,

Nomura et al. [100], used immobilized growing cells entrapped

in calcium alginate. Theamount of lactic acid produced by semi-

continuous electrodialysis fermentation using immobilized cells

was eight-times higher than that produced by non-pH controlled

fermentation, but some free cells were found in the solution.

Czytko et al. [93], found that the electrodialysis unit could only

be operated with cell free solutions in order to prevent deposi-

tion of bacteria on the membranes. To increase the productivity

of the lactic acid fermentation and to reduce the amounts of

effluents, Boyaval et al. [94] combined the cell recycle systemwith electrodialysis and obtained a lactic acid concentration of

85 g l h and a productivity of 22g l h. Siebold et al. [95], showed


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that lactic acid production with in situ electrodialysis without

ultrafiltratioon is also possible.

The two-stage electrodialysis method was described by

Glassner et al. [101]. Madzingaidzo et al. [96], presented a pro-

cess for sodium lactate purification by mono-polar electrodialy-

sis and recoveryof lactic acidby bi-polar electrodialysis. Sodium

lactate of feed concentration 125 g/l was concentrated by mono-

polar electrodialysis to a maximum of 150 g/l. A low incidence

of impurities was observed in the concentrated solutions with

less than 2 g/l glucose and 1.5g/l acetate detected. Bipolar elec-

trodialysis unit yielded 160 g/l free lactic acid while color and

otherchemicalimpuritieswere significantly reduced. The lactate

solution is passed through the bipolar electrodialysis unit to get

free lactic acid. Additional bleaching and de-ionization process

steps are followed to polish the free lactic acid for high-grade

applications.

Rathin Datta et al. [97], studied the various advantages of

bipolar electrodialysis to eliminate the salt or gypsum wasteproduced in the conventional processes in large scale lactic acid

production processes.

M. Bailly, et al. [102] suggested a complete production

scheme, targeted around membrane operations for clarification,

concentration and conversion. The fermentation broth is first

clarified by cross flow microfiltration. Divalent cations, that con-

stitute a poison in the configuration used, are then removed from

the clarified broth. Conventional electrodialysis (ED) is further

used prior to EDBM in order to increase the concentration of

ionic species, comprising the organic acid salt. In this manner,

the area of bipolar membrane required for the conversion is low-

ered so that the economical profitability of the EDBM step is

improved.

As described by Mathieu Bailly [98], electrodialysis with

bipolar membranes (EDBM) is used to prepare polymer grade

lactic acid. The process has to be simultaneously economically

attractive and have a low impact on the environment. In this con-

text, this article details the performance and cost related to an

industrial EDBM plant operated for the production of organic

acids. Over the past 15 years, not more than 12 commercial

plants totaling about 2400 m2 of Aqualytics and Tokuyamas

bipolar membranes have been installed throughout the world

for different chemicals. A complete downstream (from the fer-

mentation) process based on combined electrodialysis steps for

purification/concentrationand conversion is proposed in the caseof lactic acid.

Finally Bailly describes performances of a plant with a pro-

duction capacity 5000 tonnesof lactic acid peryear which makes

use of a two-stage electrodialysis process. An electricity con-

sumption of 1.8 kW/kg of produced acid is reported.

Habova et al. [99], confirmed that the two-stage electrodial-

ysis is a suitable and efficient technique for recovery of lactate

ions from the pretreated fermentation broth and subsequent

conversion into lactic acid. The pretreament consisted of ultra-

filtration, decolourisation and removing of multivalent metal

ions.

Several authors have carried out studies to improve the eletro-dialysis fermentation (EDF) method. [103105]. But commer-

cialization of EDF process has not been reported.

Kang, et al. [106] described nanofiltration (NF) as an alter-

native to desalting electrodialysis (ED) and ion exchange for the

recovery of ammonium lactate from fermentation broth.

Li et al. [107], developed a laboratory scale bioreactor com-

bining conventional electrodialysis and bipolar membrane elec-

trodialysis for in situ product removal and pH control in lactic

acid fermentation. The electrokinetic process enabled removal

of the biocatalytic product (lactic acid) directly from the biore-

actor system, in a concentrated form, as well as enabling good

pH control without generation of troublesome salts.

4.2. Choice of electrodialysis

Electrodialysis has been reported for sodium or ammo-

nium lactate broth. Ammonium lactate is preferred as it uses a

cheaper alkali. An electrodialysis fermentation(EDF) is promis-

ing because it can remove produced lactic acid continuously

from the fermentation and maintain the pH of the broth [103].Commercial exploitation of electrodialysis with bipolar

membranes (EDBM) is reported by Mathieu Bailly [98]. Broth

needs to be micro filtered prior to electrodialysis. Monopolar

electrodialysis is used to concentrate and purify the broth. How-

ever the output is in the form of ammonium lactate. Further

bipolar electrodialyis can convert ammonium lactate to lactic

acid. Recovered ammonium hydroxide can be reused in fer-

mentation. Addition of ammonium hydroxide in fermentation

is advantageous as it improves productivity of microorganisms.

Thus downstream process route will involve microfiltration,

monopolar electrodialysis and bipolar electrodialysis. However

this process also does not separate out other organic acids from

lactic acid.

5. Esterification and reactive distillation

High purity lactic acid can be prepared by esterification of

crude lactic acid with alcohols, distillation of ester, hydroly-

sis of the distillated lactate ester to yield the alcohol and lactic

acid. Esterification is the only downstream process, which sep-

arates other organic acids from lactic acid. Esterification gives

esters of lactic acid and further hydrolysis of esters is neces-

sary to get the product as lactic acid. Simultaneous distillation

with esterificationhydrolysis is called reactive distillation. Fer-

mented broth containing lactic acid needs to be pretreated toremove some impurities before reactive distillation using resin

beds as catalyst as well as bed for distillation column.


Smith and Claborn [108], described methods for the prepara-

tion of purified lactic esters from crude lactic acid obtained from

fermentation. To obtain high yields of the pure lactic esters with

alcohol containing less than four carbons, it is necessary to use

a large excess of alcohol during esterification and then rapidly

remove water with excess alcohol from the ester at low temper-

ature, preferably in vacuum with aid of an efficient fractionatingcolumn. Calcium lactate is dissolved in methanol and equiva-

lent amount of sulphuric acid is added to liberate the lactic acid


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to precipitate and separate calcium sulphate. Lactic acid solu-

tion is heated for 48 h at refluxing temperature to complete the

esterification. Similarly method for preparation of lactic esters

insoluble in water was also presented.

Filachione and Fisher [109], described a method for purifi-

cation of lactic acid by preparation of methyl lactate from crude

aqueous lactic acid. The method comprises of passing methanol

vapor through aqueous lactic acid and condensing the efflu-

ent vapors. The condensate, a mixture of methanol, water and

methyl lactate, can be distilled to recover the methyl lactate and

hydrolyzed to obtain purified lactic acid.

Schopmeyer et al. [110], suggested heating an esterification

mixture of lactic acid (4060 wt.%), a relatively low boiling

aliphatic alcohol, and an acidic catalyst (sulphuricacid) for ester-

ifiation in a jacketed kettle. The vapors from the esterification

kettle are continuously fed to a fractionating column, which may

contain alcohol, ester and water. Continuous hydrolysis of ester

in a fractionating column is done at atmospheric pressure. Alco-hol produced by hydrolysis is removed fromthe top and returned

to esterification kettle, and lactic acid along with water is drawn

from the bottom.

Recently reactive distillation has drawn considerable atten-

tion because of its striking advantages, especially for

equilibrium-limited reactions. Purification of lactic acid through

reactive batch distillation was investigated by several investi-

gators [111113]. The experimental setup used by the authors

consisted of two columns for separation of reactants from the

product and two reboilers for esterification reaction and hydrol-

ysis reaction. The feed consisted of only 1020% lactic acid by

weight.

Choi et al. [114], studied batch distillation of lactic acid with

simultaneous reactions. Lactic acid was reacted with methanol,

and methyl lactate was produced by the esterification reaction in

presence of cation exchange resin (Dowex 50W). The volatile

methyl lactate was distilledsimultaneouslywith hydrolysisreac-

tion forming lactic acid. To recover pure lactic acid through two

reactions and distillation, batch distillation system consisting of

two condensers, feed vessel, and reboiler was used. The yield of

recovered lactic acid was as high as 95%. When impure lactic

acid solution obtained from bacterial fermentation was used as

feed, highly pure lactic solution was obtained with yield of 92%

in reboiler.

Seo et al. [111], studied the feasibility of recovery of lacticacid by two batch reactive distillations using cation exchange

resin (Dowex 50 W) as a catalyst and glass packed column.

For the recovery of lactic acid, two reactions, esterification and

hydrolysis, are involved and hence, an apparatus with two dis-

tillation columns was developed and operated in a batch mode

to ensure enough residence time in the reboiler and column. The

effects of operating variables such as catalyst loading, mole ratio

of lactic acid to methanol, feed concentration, type of alcohols

and partial condenser temperature on yield were studied. The

reaction products of the esterification (methyl lactate and water)

were distilled to the hydrolysis part to recover into pure lactic

acid. The yield of lactic acid increased as catalyst loading in theesterification part was increased. The decrease in mole ratio of

lactic acid to methanol, and lactic acid feed also improved the

yield of lactic acid. Methanol as a reactant gave higher yield

than any other alcohol. The yield of lactic acid was as high as

90%.

Kim et al. [112], also carried out similar studies using Old-

ershaw columns and reboilers for fractionation and reactions.

Concentration and temperature profiles in the reboilers and on

each stage were investigated throughout the operation. Six hour

operating time was required for getting high purity lactic acid.

The effect of columns on the recovery yield was investigated.

The column improved the fractionation of the boilups from the

reboilers. More effective fractionation in columns allowed vapor

streamin columns to contain more methanol and liquid streamto

contain less methanol. Thereby, methanol-concentrated recycle

flow was obtained more effectively and methanol was prevented

to remain in hydrolysis part. That resulted in the more effective

reaction in both reboilers and improved the yield.

Kim et al. [113], studied reactive batch distillation similar to

Kim et al. [112]. Methanol recycle and feeding method wereinvestigated as the factors, which could control the component

boilup rate of each species and rate of esterification reaction.

The temperature of partial condenser controlled the flow rate

and composition of methanol recycle stream. Semi batch oper-

ation was compared with batch operation. Continuous feeding

of methanol enhanced the recovery system performance while

continuous feeding of lactic acid aqueous solution, deteriorated

the recovery compared with batch operation.

In continuous esterification, the mixture of an aqueous solu-

tion of lactic acid to be purified, a relatively low boiling aliphatic

alcohol, and an acidic catalyst of esterification is heated to pro-

duce mixture of vapors. Use of sulphuric acid as catalyst may

result in traces of acid in the product. In presence of impurities

with cation exchange resin catalyst it may be difficult to main-

tain the operation at steady state. Therefore it may be necessary

to purify the crude lactic acid from impurities like residual sugar

and protein before hand.

The two column reactive distillation scheme studied by Seo

et al. [111], Kim et al. [112], Kim et al. [113], is for upto 30%

crude lactic acid feed. And the catalyst used for the studies for

both esterification and hydrolysis is cation exchange resin i.e.

DOWEX 50W. This scheme with feed of 5060% lactic acid

concentration may reduce the size of equipment.

The reported yield of the ester vary from about 60 to 100%,

depending largely upon the method used for removing the wateras it is formed during the esterification reaction. It is more dif-

ficult to obtain a high yield of ester with methyl or isopropyl

alcohol than with a long chain alcohol such as butyl, amyl,

acetyl, lauryl, and stearyl, because the lower alcohols and the

corresponding lactic esters are soluble in water. It is necessary,

therefore, to resort to other methods for removing this water or

reducing the ratio of water to alcohol in the reacting mixture by

using a large excess of alcohol.

Recently, Sun at al.[115], studied conversion of LA or ammo-

nium lactate (NH4LA) into esters and subsequent hydrolysis

of the purified ester into LA to obtain highly pure LA. In this

study, using two reactors with a rectifying column were used torecover LA from the fermentation broth. NH4LA obtained by

fermentation was used directly to produce butyl lactate by react-


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