REVIEWS

Fermentation of Glucose to Lactic Acid Coupled with ReactiveExtraction: A Review

Kailas L. Wasewar, Archis A. Yawalkar, Jacob A. Moulijn, andVishwas G. Pangarkar*,

Mumbai University Institute of Chemical Technology, Matunga, Mumbai 400019, India, andReactor and Catalysis Engineering, Delft Chem Tech, Delft University of Technology,Julianalaan 136, 2628 BL Delft, The Netherlands

Growing demand for biodegradable polymer substitutes for both conventional plastic materialsand new materials of specific uses such as controlled drug delivery or artificial prostheses drawsattention to the need for improvement of conventional processes for lactic acid production.Reactive extraction with a specified extractant giving a higher distribution coefficient has beenproposed as a promising technique for the recovery of lactic acid. A critical analysis of theavailable literature data has been made, and some general conclusions have been drawn. Asuitable extractant-diluent system for lactic acid extraction on the basis of distributioncoefficient, toxicity, and feasibility for backextraction is suggested. Also, methods for back-extraction and recovery are suggested.

1. Introduction

For the last 2-3 decades, because of the sharpincrease in petroleum costs, there has been a resurgenceof interest in large-volume production of fermentationchemicals, and the potential role of a new energy-efficient fermentation technology is receiving growingattention.

The current economic impact of fermentation chemi-cals, however, is still limited, in large part because ofdifficulties of product recovery. Thus, for fermentationproducts to penetrate the organic chemicals industry,substantial improvements in the existing recoverytechnology are needed.

Lactic acid is a commodity chemical produced byfermentation and utilized in the food, chemical, andpharmaceutical fields. Lactic acid is an importantchemical that can be converted to propylene glycol,acrylic polymers, and polyesters. Lactate esters derivedfrom biolactic acid are being considered as alternativebenign solvents.1 In particular, an interesting applica-tion is the use of lactic acid as a monomer for thesynthesis of biodegradable homopolymers and copoly-mers.2,3 Lactic acid is a raw material for the productionof biodegradable poly(lactic acid). A growing demand forbiodegradable polymers, substitutes for both conven-tional plastic materials and new materials of specificuses such as controlled drug delivery or artificialprostheses, draws attention the need for improvementof conventional processes for lactic acid production.4

The world market of lactic acid is growing every year.The level of production is around 350 millions kgyear-1,5 and the worldwide growth is believed by someobservers to be 12-15% year-1.6

In December 1994, market prices in the U.S. for bothfermentation and synthetic food-grade 50 and 88% lacticacid were $0.71 and $1.15 lb-1 ($1.56-2.53 kg-1),respectively. Technical-grade 88% lactic acid was quotedat $1.12 lb-1 ($2.47 kg-1).7

In April 2003, market prices in the U.S. for 88% food-grade and technical-grade lactic acid were $0.77 and$0.7 lb-1, respectively. The 50% solution for grade lacticacid was $0.59 lb-1.8 These prices were 50% lower thanthe prices of year 1994, illustrating the economics ofscale based on the increasing use of lactic acid.

Recovery of lactic acid from aqueous solutions is agrowing requirement in fermentation-based industriesand so is recovery from waste streams. Lactic acid canbe produced by the fermentation of biomass. For theproduction of lactic acid, the pH is very important andmust be maintained between 5.5 and 6.5. However,during fermentation, the accumulation of lactic aciddecreases the pH of the fermentation broth and theactivity of the lactic acid producing bacteria decreases.Hence, the lactic acid accumulation inhibits the productformation. Also, if levels of free lactic acid reach 1-2wt % of total combined lactic acid, then the bacteria arelikely to die.9,10 The traditional recovery process of lacticacid from fermentation broth is quite complicated.Isolation of this acid from dilute solution or fermentationbroths is an economic problem because the vaporizationof water consumes much energy and a direct upgradingof the dilute solution by evaporation is inefficient. Lacticacid is nonvolatile, and hence distillation is not useful.In conventional processes, lactic acid has been recoveredfrom the fermentation broth by precipitation of calcium

* To whom correspondence should be addressed. Tel.:+91-22-24145616. Fax: +91-22-24145614. E-mail: vgp@udct.org, v_pangarkar@hotmail.com.

Mumbai University Institute of Chemical Technology. Delft University of Technology.

5969Ind. Eng. Chem. Res. 2004, 43, 5969-5982

10.1021/ie049963n CCC: $27.50 2004 American Chemical SocietyPublished on Web 07/31/2004

lactate with calcium hydroxide. In this recovery scheme,calcium lactate is precipitated, recovered by filtration,and converted to lactic acid by the addition of sulfuricacid. The dilute lactic acid product is then sequentiallypurified using activated carbon, evaporation, and crys-tallization. These separation and final purificationstages account for up to 50% of the production costs.11,12Thus, this method of recovery is expensive and un-friendly to the environment because it consumes limeand sulfuric acid and also produces a large quantity ofcalcium sulfate sludge as solid waste.13 Because of thedetrimental effect of low pH, reactor productivities arelow and the products are obtained in a dilute form. Theeffects of end-product inhibition can be reduced by insitu removal of lactic acid from fermentation broth byseveral methods.

A number of processes for lactic acid recovery fromfermentation broth without precipitation have beenstudied and reported in the literature: solvent extrac-tion,14-30 membrane bioreactor,31-33 liquid surfactantmembrane extraction,34 adsorption,35-39 direct distilla-tion,40 electrodialysis,41-46 reverse osmosis,47 anionexchange,48-50 etc.

Electrodialysis and dialysis have the problem ofmembrane fouling, which requires frequent cleaning ofthe dialyzer. Moreover, large-volume dialysis units, evengreater than the volume of the fermentor vessel, wouldbe required in a commercial-scale unit.9 Electrodialysisgives a higher extent of lactic acid separation but withincreased power and energy consumption.9 Also, largeamounts of byproduct salts from the ion-exchangeregeneration are formed. Adsorption or the ion-exchangeprocess requires regeneration of an ion-exchange resinand adjustment of the feed pH to increase the sorptionefficiency, requiring large amounts of chemicals.46 Dur-ing direct distillation, high-boiling internal esters asdimers and polymers can be formed.40 In the extractionof lactic acid from fermentation broth with microporoushollow fiber membranes, there is a tendency to form anemulsion.33 Liquid surfactant membrane extractionexhibits a high complexity of operation due to swellingof the membranes in liquid surfactants.50 Supportedliquid membranes often suffer from membrane instabil-ity.50

Reactive extraction with a specified extractant givinga higher distribution coefficient has been proposed as apromising technique for the recovery of carboxylic andhydroxycarboxylic acids.14,51,52 Reactive liquid-liquidextraction has the advantage that lactic acid can beremoved easily from the fermentation broth, preventinglowering of the pH. Further, lactic acid can be re-extracted and the extractant recycled to the fermenta-tion process.53,54

A large number of literature studies are available onthe reactive extraction of lactic acid. Reactive extractionstrongly depends on various parameters such as thedistribution coefficient, degree of extraction, loadingratio, complexation equilibrium constant, types of com-plexes (1:1, 2:1, etc.), rate constant of lactic acid-aminereaction, properties of the solvent (extractant anddiluent), type of solvent, temperature, pH, acid concen-tration, salt present in the acid, water coextraction,toxicity, feasibility of backextraction, and solvent forbackextraction. The results of these studies of the aboveparameters are available in a scattered form. In thepresent work, an attempt is made to combine the

available data on the reactive extraction of lactic acidand to discuss the same in a concise manner.

A critical analysis of the available literature data hasbeen made, and some general conclusions concerningthe above-mentioned parameters have been drawn.

2. Types of Extractants

A good starting point for developing a new extractiverecovery process for lactic acid should be the identifica-tion of novel, more powerful extractants. In the reactiveextraction of lactic acid, the extraction system mustfulfill two basic requirements: a high distributioncoefficient (KD)

and a high selectivity for lactic acid.Further requirements of an extractant or a system

of extractants are55 (i) low viscosity, (ii) higher densitydifference between the extractant and raffinate, (iii) amedium interfacial tension, (iv) thermal stability, (v) lowenthalpy of vaporization, (vi) low melting points, (vii)no reaction between the extractant and raffinate, (viii)low solubility of the extractant in the raffinate, (ix) lowtoxicity and good biological degradability, and (x) lowprice and good availability.

Kertes and King17 categorized the extractant intothree major types: (I) conventional oxygen-bearinghydrocarbon extractants [methyl isobutyl ketone (MIBK),octanol, decanol, etc.], (II) phosphorus-bonded oxygen-bearing extractants (tributyl phosphate, etc.), and (III)high molecular weight aliphatic amines (Aliquat,Alamine, etc.).

The first two categories are nonreactive extractantsand involve the solvation of the acid by donor bonds,which are to be distinguished from strong covalentbonds and from ionic interactions. In category III, achemical reaction is involved. The distinction betweenthe first two categories is based on the strength of thesolvation bonds and the specificity of solvation.17

The conventional extractants, such as ketones, ethers,and alcohols, are not able to fulfill the basic require-ments often because of their low distribution coef-ficients. The values of KD of lactic acid in variousextractants are given in Table 1. It can be seen thatthe distribution coefficient of lactic acid is low (

affinity of the organic base for the acid gives selectivityfor the acid over nonacidic components in the mixture.62

Primary amines yield a high mutual solubility withwater. Secondary amines can give quite high values ofKD but are subject to amide formation during regenera-tion by distillation. Primary alkylammonium lactateseither are excessively water-soluble at room tempera-ture or exhibit surface-active properties or both. Lac-tates of secondary aliphatic amines are more stable andorganic solvent soluble, although gel formation inter-feres with phase separation. This trend of the extractionpower is, of course, dictated by the basicity of theamine.17 KD for secondary amines is much more de-pendent upon the amine structure than is the case fortertiary amines.63

Table 1 shows that the values of KD for tertiaryamines alone are slightly higher than those of otherextractants. However, as discussed later, a propercombination of conventional tertiary amine and con-ventional extractant (diluent) gives significantly highervalues of the distribution coefficient.

For tertiary amine extractants, KD for lactic acidtypically exhibits a maximum value at an intermediatesolvent composition. This behavior apparently reflectsthe combined effects of mass action for the chemicalreaction, on the one hand, and the activity coefficientof the reaction complex in the solvent mixture, on theother hand.63

The proton association constant is highest for tertiaryamines and increases with the number of carbon atoms,although the nature of the diluent also has a markedeffect on the magnitude of the proton associationconstant.17 Also, tertiary amine extractants are effectivewith KD strongly dependent upon the nature of thediluent used and the concentration of amine in thatdiluent.63 The extractive capacity of tertiary aminesexceeds that of the primary and secondary ones signifi-cantly.

The diluent affects the basicity of the amine and thusthe stability of the ion pair formed and its solvation.The stability of the complex governs the equilibrium

conditions of acid extraction, especially at low loadingratios, where the equilibrium aqueous acid concentra-tion is very low. Under such conditions, polar diluentsare more favorable than the zero-polarity, low dielectricconstant, aliphatic and aromatic hydrocarbons.17,66 Junget al.55 found that the distribution coefficient wasinversely proportional to the molar weight of the alco-hols. More electronegative groups serve to decrease KDbecause a decrease in the electron-donating ability ofthe carbonyl oxygen diminishes its Lewis basicity.14 Thesolvation of the whole amine acid complex is based ondipole-dipole interaction and was found to play animportant role in the neutralization reaction betweenacid and amine, which is promoted by increasing thepolarity of the diluent.

Yang et al.62 and Choudhury et al.67 studied theinteraction of carboxylic acids with tertiary and qua-ternary amines. The quaternary amine Aliquat 336 waseffective in the extraction of both dissociated andundissociated forms of acids, whereas the tertiary amine[Alamine 336 and trioctylamine (TOA)] could extractonly the undissociated acid. The polar diluent, octanol,increased the extracting power of the tertiary amine byproviding more solvating capacity for the nonpolaramine. In contrast, neither the polar nor the nonpolardiluent was active when used with Aliquat 336.62Tertiary amines are capable only of extracting undis-sociated acid and cannot be used under basic conditions.In contrast, quaternary amines can extract acid underboth acidic and basic conditions. However, this maybecome disadvantageous because it makes Aliquat 336much more difficult to strip.62

From the above discussion, it can be concluded thattertiary amines in diluents are the best suitable extrac-tants for the extraction of lactic acid. One of the basiccriteria for the selection of the most effective system ofextractant is the distribution coefficient. Values ofdistribution coefficients of lactic acid in various amine-diluent compositions are given in Table 2. It is foundthat 30% Alamine 336 in octanol has the highest valueof KD. The data in Table 2 suggest that higher concen-trations of Alamine in diluent may give higher KD.Indeed, San-Martin et al.69 found that the degree ofextraction increased up to a concentration of 40%Alamine 336 in toluene and then remained constant asa maximum equilibrium concentration was reached.However, higher concentrations of Alamine 336 increasethe viscosity of the organic phase, which is not favorablefor extraction. Moreover, for extractions with highconcentrations (>25%) of amine in diluent, a thirdemulsion phase was observed at the interface betweenthe aqueous and organic phases.62 Hence, these authorssuggested the use of 10-20% Alamine 336 in diluent.

3. Lactic Acid-Amine (Tertiary) Complex

In the previous section, it was found that tertiaryamine, Alamine 336, is the best suitable extractant forreactive extraction of lactic acid, and hence in thissection only the lactic acid-amine complex is discussed.The fundamental difference between oxygen- and ni-trogen-bearing basic extractants in the extraction ofacids originates from the basic behavior of the acidproton during the transfer from an aqueous to anorganic solution. In the systems with oxygen-bearingsolvents, whether carbon, phosphorus, or sulfur isbound, the acid strength in the aqueous solution andthe hydrogen bond in the organic solution determine the

Table 1. Distribution Coefficients for Lactic Acid inVarious Solvent-Water Systems

solvent KD ref

diethyl ether 0.1 17diisopropyl ether 0.04 17MIBK 0.14 17MIBK 0.13 56MIBK 0.1 57octanol 0.32 17octanol 0.31 53decanol 0.29 58m-cresol 0.31 18chloroform 0.11 18hexane 0.0003 59chlorobenzene no extraction 601-chlorobutane no extraction 60chloroform no extraction 60methylene chloride 0.05 60MIBK 0.01 601-decanol 0.01 601-octanol 0.15 60tributyl phosphate 0.71 60tri-n-pentylamine 0.35 61tri-n-hexylamine 1.27 61tri-n-octylamine 0.63 61tri-n-decylamine 0.35 61Alamine 336 0.76 61Aliquat 336 2.17 62Alamine 336 0.55 62

Ind. Eng. Chem. Res., Vol. 43, No. 19, 2004 5971

extractability. On the other hand, the acid extracted intoan amine-containing organic phase is no longer to beregarded as an acid but as an ammonium salt. It is thusthe extent of ion-pair association between the alkyl-ammonium cation and the acid radical that determinesthe extractability or, more precisely, the stability of theorganic-phase species.17

Thus, the extraction process is based on an acid-base-type reaction between the amine B and the lactic acidHL

where KE is the equilibrium complexation constant.Generally, the simple stoichiometric reaction (eq 2)

is not suitable for describing the formation of a complexof acid and amine molecules because the organic phaseextracts more acid than would be expected on the basis

of a 1:1 complex.17,56,58,69,71 Though the exact nature ofthe chemistry involved in the uptake of extra acid isnot known and despite the obvious nonideality of theorganic phase under these conditions, distribution datacan be interpreted in terms of simple mass actionequations of the type17

The extent to which the organic phase (amine +diluent) can be loaded with the acid is expressed as theloading ratio, z.

The loading ratio, z, can be related with the equilibrium

Table 2. Distribution Coefficients for Lactic Acid in Various Solvent Mixtures-Water Systems

extractant diluent KD ref

15% Alamine 336 oleyl alcohol 3 6830% Alamine 336 oleyl alcohol 4.5 6850% Alamine 336 oleyl alcohol 6.5 6820% Alamine 336 MIBK 0.72 5630% Alamine 336 MIBK 2.68 5640% Alamine 336 MIBK 4.24 5620% Alamine 336 decanol 12.57 5830% Alamine 336 decanol 16.44 5840% Alamine 336 decanol 23.37 5810% Alamine 336 octanol 15.35 5320% Alamine 336 octanol 19.69 5330% Alamine 336 octanol 25.95 5350% Aliquat 336 kerosene 0.90 6225% Aliquat 336 kerosene 0.20 6250% Aliquat 336 2-octanol 0.78 6250% Alamine 2-octanol 2.50 62tri-n-hexylamine (12.2 alcohol-amine molar ratio) 1-butanol 22.1 55tri-n-hexylamine (12.2 alcohol-amine molar ratio) 2-butanol 12.5 55tri-n-hexylamine (12.2 alcohol-amine molar ratio) isobutyl alcohol 23.6 55diethylbutylamine (0.97 mol L-1) chloroform 1.8 66tributylamine (0.97 mol L-1) chloroform 1.4 66triamylamine (0.97 mol L-1) chloroform 2.7 66TOA (0.97 mol L-1) chloroform 4.5 66Alamine (0.4 mol L-1) toluene 0.83 69Alamine (0.8 mol L-1) toluene 2.06 6950% di-n-hexylamine oleyl alcohol 0.757 6150% di-n-octylamine oleyl alcohol 11.1 6150% di-n-decylamine oleyl alcohol 7.76 6150% tri-n-pentylamine oleyl alcohol 0.72 6150% tri-n-hexylamine oleyl alcohol 2.94 6150% tri-n-octylamine oleyl alcohol 1.90 6150% tri-n-decylamine oleyl alcohol 1.66 6150% Alamine 336 oleyl alcohol 2.62 6150% TOA MIBK 3.75 6730% TOA octanol 0.90 6790% TOA octanol 1.2 6790% TOA paraffin liquid 0.4 67TBP (3 mol dm-3) hexane 0.75 70TBP (3 mol dm-3) + n-octylamine (0.3 mol dm-3) hexane 0.17 70TBP (3 mol dm-3) + di-n-hexylamine (0.3 mol dm-3) hexane 0.51 70TBP (3 mol dm-3) + TOA (0.3 mol dm-3) hexane 3.4 70TBP (3 mol dm-3) + triisooctylamine (0.3 mol dm-3) hexane 1.5 70TBP (3 mol dm-3) + triethylhexylamine (0.3 mol dm-3) hexane 0.78 70TBP (3 mol dm-3) + TOA (0.2 mol dm-3) hexane 2.4 70TBP (3 mol/dm3) + TOA (0.3 mol dm-3) butyl acetate 2.8 70TBP (3 mol dm-3) + TOA (0.3 mol dm-3) toluene 2.8 70TBP (3 mol dm-3) + TOA (0.3 mol dm-3) chlorobenzene 3.0 70TBP (3 mol dm-3) + TOA (0.3 mol dm-3) 1-decanol 2.9 70

HLaq + Borg 798KE1

BHLorg (2)

KE )[BHL]org

[B]org[HL]aq(3)

nHLaq + BHLorg 798KEn

BHL(HL)n,org (4)

KEn )[BHL(HL)n]org

[BHL]org[HL]aqn

(5)

z )[HL]org[B]T,org

)[HL]org

[B]org + [BHL(HL)n]org(6)

5972 Ind. Eng. Chem. Res., Vol. 43, No. 19, 2004

complexation constant for a n:1 lactic acid-aminecomplex by the following equation:

For very dilute, slightly loaded organic solutions,when z e 1, a 1:1 lactic acid-amine complex is formed.Formation of a 1:1 lactic acid-amine complex is com-mon, and its structure is shown in Figure 1a. Theformation of 2:1 and 3:1 lactic acid-amine complexesdepends on the lactic acid concentration in the aqueousphase, and the ratio of 1:1 to 2:1 complex formation isdiluent dependent.18 At higher concentrations of lacticacid, the 2:2 and 3:1 complexes can be formed.22,56,58 Thisoverloading phenomenon results from a second lacticacid molecule hydrogen bonding to the lactic acid thatis already involved in the 1:1 complex (Figure 1b). Athird lactic acid molecule can then hydrogen bond to thesecond one in the same way, enabling loadings abovetwo, and the 3:1 complex is shown in Figure 1c.

Different diluents solvate the various complexes andthe amine to different extents, thereby changing theactivity coefficients. Generally, the greater the ionizingacidity of the acid, as measured by pKa, the more it isextracted. The strength of solvation of the complex bythe diluent decreases in the following order:18 alcohol(e.g., 2-ethyl-1-hexanol) > nitrobenzene > proton-donat-ing halogenated hydrocarbon (e.g., methylene chloride,chloroform, and 1,2-dichloroethane) > ketone (e.g.,MIBK, diisobutyl ketone, and 2-heptanone) > halo-genated aromatic (e.g., dichlorobenzene and chloro-benzene) > benzene > alkyl aromatic (e.g., toluene andxylene) > aliphatic hydrocarbon (e.g., hexane, heptane,and octane).

Juang and Huang27 also observed the formation ofthree complexes of lactic acid with TOA. The values of

the equilibrium complexation constants of a lactic acid-amine complex in various diluents are shown in Table3. In many studies, the complex 3:1 is not favoredbecause the concentration of lactic acid in the organicphase is not high enough. This situation (because thereis low concentration,

effect is relatively small in the extraction with tributylphosphate only.

It is found that the effect of the temperature on theextraction of lactic acid depends on the diluent andextractant. Generally, the effect of the temperature onthe extraction of lactic acid with diluents only is verylow. However, extraction decreases with an increase intemperature when an amine-diluent system is used.

5. Thermodynamics of the Lactic Acid-AmineComplex

As discussed in section 4, because of the exothermicnature of the complexation reaction and the decreasein entropy in the same, the amount of lactic acidextracted decreases with an increase in the extractiontemperature.

If the enthalpy and entropy of reaction are assumedto be constant over the short temperature range ofrelevance to industrial practice, the expression

predicts that a plot of ln K vs 1/T gives a straight line.The slope is proportional to the enthalpy change of thereaction, and the intercept is proportional to the entropychange.

The values of H and S for the formation of 1:1, 2:1,and 3:1 lactic acid-Alamine 336 complex in MIBK andchloroform are shown in Table 6.74 The enthalpies ofthe lactic acid-Alamine 336 complex are more exo-

thermic in chloroform than in MIBK. The entropydecrease is greater in chloroform than in MIBK.

Tamada and King74 found that the 1:1 lactic acid-Alamine 336 complexation is much more exothermic andinvolves a much greater loss of entropy than theformation of 2:1 or 3:1 lactic acid-Alamine 336 com-plexes. They concluded that the 1:1 lactic acid-Alamine336 complexation involves the formation of an ion pair,but higher complexes involve hydrogen-bond formation.

A comparison of the thermodynamic parameters for2:1 complex formation of lactic acid with the amine inchloroform and MIBK reveals a contrast to the 1:1behavior. In chloroform, H21 is a small, positivequantity, indicating an increase in the system entropyupon the addition of the second acid molecule to the 1,1complex. This is consistent with the hypothesis thatchloroform orders itself around the 1:1 complex. Theaddition of the second molecule disrupts the chloroform-complex interaction, which requires energy and in-creases the overall randomness of the system.74 Tamadaand King74 compared the values of the heat of mixingin an aqueous phase, heat transfer from the organic toaqueous phase, and enthalpy and entropy of complexesof lactic acid with those of succinic acid and found thatit is possible to relate the heat of mixing of the acid indiluent with the heat of mixing of the complex in thesolvent.

6. Effect of the pH on Extraction

There has been increasing interest in using anaerobicbacteria for organic acid production from biomass.However, the use of these bacteria for acid productionis usually limited by the low acid concentration (

336 in kerosene.62 The KD value increased with adecrease in the pH except at extremely high or low pHs,where KD does not change significantly with the pH.62

Because literature reports indicate that the optimumpH values for the fermentation and extraction of lacticacid are different, Choudhury et al.67 studied the effectsof the initial pH (pH ) 2, 4, and 6) on the extraction oflactic acid by TOA and Aliquat 336 in MIBK, octanol,and paraffin liquid. They concluded that a lower pHfavors the extraction of lactic acid for both of theextractants. Because the formation of a quaternaryammonium salt is the first step in the extraction of lacticacid by TOA, the extraction will be greater at acidic pH.However, in the case of Aliquat 336, because of itsquaternary amine nature, the extraction of lactic acidwas less influenced by the pH of the aqueous phase incomparison with the tertiary amine, TOA.

pH is directly related with lactic acid concentration.The distribution coefficients are higher at lower acidconcentrations when aqueous acid concentrations arebelow 10 g L-1.52,63 Generally, the distribution coefficientis constant for a low concentration of lactic acid anddecreases for higher concentration.56,58 Hence, it isbeneficial to carry out reactive extraction at a lowerlactic acid concentration for a high distribution coef-ficient, which requires a smaller amount of extractantand also avoids the product inhibition of microorganismsdue to the acid. The situation may, however, change ifmicrobial strains that can tolerate higher lactic acidconcentrations are developed and made available forindustrial use.

7. Water Coextraction

The mutual solubility between an aqueous solutionand a given solvent at a fixed temperature is affectedby the nature of the acid and its concentration. Withweak organic acids, mutual solubilities cause substan-tial volume change.17 The extent of the volume changeis, of course, related to the coextraction of water alongwith that of the acid. The organic-phase volume in-creased about 10% with corresponding decreases in theaqueous phase when Aliquat 336 was used.62 On theother hand, Yang et al.62 observed no significant volumechange when Alamine 336 was used. For extractionswith high concentrations (>25%) of amine in diluent, athird emulsion phase was also observed at the surfacebetween the aqueous and organic phases.62 Volumechange depends on the type of diluent and the type andconcentration of extractant as well as temperature.

The volume change in the extraction is related withthe coextraction of water. Water coextraction, i.e., waterthat enters the organic phase with the solute, may also

affect process economics. For example, it may be neces-sary to recover pure acid from an aqueous solutionproduced from the extract during regeneration.

Starr and King80 found that water removal from theorganic phase could decrease the solubility of carboxylicacid. This phenomenon was applied for the strippingmethod of carboxylic acid by the removal of water fromthe organic phase. The amounts of coextracted waterand lactic acid extracted are increased with an increasein the number of moles of TOA. However, the type ofactive diluent is a more important factor than thenumber of moles of TOA for extraction of lactic acid.60

Han and Hong60 introduced the sensitivity index,which represents the amount of lactic acid extractedwith the variation of the water content in the organicphase. This was defined as the inverse of the slope ofthe amount of lactic acid extracted versus the watercontent in the organic phase. The sensitivity indices invarious diluents for three types of active diluentscontaining chlorine atoms, carbon-bonded oxygen donoractive diluents, and phosphorus-bonded oxygen donoractive diluents are given in Table 7. The sensitivityindex decreases in the order active diluents containingchlorine atoms > carbon-bonded oxygen donor activediluents > phosphorus-bonded oxygen donor activediluents.

Tamada and King74 performed studies to compare thecoextraction of water, which accompanies the extractionof various other acids by Alamine 336 in chloroform,MIBK, and various alcohols. Monocarboxylic acids carryless water with them than dicarboxylic acids, which mayreflect the tendency of coextracted water molecules toassociate with the carboxylate group.74 Tamada andKing74 found that, for the extraction of lactic acid byAlamine 336 in chloroform and MIBK, water coextrac-tion increases with increasing temperature.

In general, selectivity of the acid over water in theextraction by amine extractants is high relative to theresults with conventional solvents. The water carriedinto the extract would be minimal compared to theamount of water used in an aqueous backextraction, andtherefore it has little effect upon process viability.18

8. Effect of Lactose and Salt on Extraction

To study the influence of salt (NaCl) and lactose onthe extraction of lactic acid, San-Martin et al.69 carriedout several experiments to determine the distributionequilibrium of lactic acid. Their results indicated thatthe extraction of lactic acid with Alamine 336 dissolvedin toluene is not affected by lactose. Variations of the

Figure 2. Effect of the pH on the distribution coefficient for lacticacid extraction with 50% Aliquat 336 in kerosene. Reproduced withpermission from Yang et al.62 Copyright 1990 American ChemicalSociety.

Table 7. Sensitive Indexes of Lactic Acid in VariousDiluentsa

type of diluent diluentsensitivity

index

averagesensitivity

index

diluent containing methyl chloride 1.87 2.62chlorine atoms 1-chlorobutane 2.04

chlorobenzene 2.28chloroform 4.27

carbon-bonded MIBK 0.61 0.68oxygen donor 1-octanol 0.68diluent 1-decanol 0.74

phosphorus-bondedoxygen donordiluent

tributyl phosphate 0.48 0.48

a Adapted from Han and Hong.60 Copyright 1998 MarcelDekker.

Ind. Eng. Chem. Res., Vol. 43, No. 19, 2004 5975

distribution coefficient of lactic acid for various sodiumchloride concentrations in the aqueous phase are givenin Table 8. It can be seen that if sodium chloride ispresent, less lactic acid is extracted by the organicphase. This was explained by San-Martin et al.69 byassuming that chlorine from sodium chloride and H+ion from lactic acid yield hydrochloric acid, which isextracted by the amine. This may be due to a strongeracid like HCl competing for the reaction with the amine.They also found that the chloride extraction does nottake place in the absence of lactic acid.

9. Kinetics

Wasewar et al.53,56,58 studied the kinetics of reactiveextraction of lactic acid using Alamine 336 in variousdiluents (MIBK, decanol, and octanol). They used thetheory of extraction accompanied by a chemical reaction.Doraiswamy and Sharma81 have given an exhaustivediscussion on the theory of extraction accompanied bya chemical reaction. Four regimes of extraction ac-companied by reaction (very slow, slow, fast, andinstantaneous) have been identified depending upon thephysicochemical and hydrodynamic parameters. Whenthe reaction is reversible, the solute has a finite equi-librium concentration in the bulk and the driving forceneeds to be modified by incorporating the equilibriumconcentration. The extraction involves partitioning ofthe solute available in the aqueous phase to the organicphase.

The solute A partitioned in the organic phase com-bines with the organic reactant (amine), B, accordingto

Using the guidelines given by Doraiswamy and Shar-ma,81 Wasewar et al.53,56,58 found that in a stirred cellthe system belongs to regime 3, extraction accompaniedby a fast general order chemical reaction occurring inthe diffusion film; the expression for regime 3 is

The reaction was found to be zero-order in Alamine336 and first-order in lactic acid. The rate constants forthe lactic acid-Alamine reaction in various diluents aregiven in Table 9. Table 9 indicates that octanol is abetter solvent than the other two solvents based onkinetic considerations.

Wasewar et al.54 studied the kinetics for the back-extraction of lactic acid from a loaded organic phase(lactic acid + Alamine + octanol) using aqueous tri-methylamine (TMA). The theory of extraction accom-

panied by chemical reaction was used to obtain thekinetics. The reaction between lactic acid and aqueousTMA in a stirred cell falls in regime 3, extractionaccompanied by a fast chemical reaction occurring inthe diffusion film. The reaction was found to be zero-order in TMA and first-order in lactic acid with a rateconstant of 16.67 s-1.

10. Toxicity

The presence of an organic solvent can give rise to aseries of physical microbial and biochemical effects onthe catalytic activity of the microorganisms. Toxicity ofthe organic solvent and extractant to microbes is thecritical problem in extractive fermentation. The degreeof toxicity depends on the combination of microbe andextractant solution used. Bar and Gainer78 attemptedto develop extractive fermentations for lactic, citric, andacetic acids and encountered problems of solvent toxicityand poor extraction. Brink and Tramper82 reported thatthe least toxicity is expected from solvents of lowpolarity in combination with high solvent molecularweight. Avoidance of direct contact of the organism withthe organic, amine-bearing phase can substantiallyreduce toxic effects.

To reduce the solvent toxicity, several investigatorshave used membranes to prevent direct contact of thesolvent with the cell containing broth.83-85 Immobiliza-tion is another method to protect the cells by reducingthe contact of the immiscible solvent with the microbes.

Matsumura and Markl83 attempted to make a Pora-pack Q barrier to solvent molecules beneath the surfaceof gel beads as a protection against octanol dissolved inthe medium. A calcium alginate immobilized gel system,with entrapped vegetable oil, has been reported toprovide protection from octanol, benzene, phenol, andtoluene.86

With regard to solvent toxicity, Bar and Gainer78 havedifferentiated the toxicity of the solvent due to thesoluble portion of the solvent (molecular level toxicity)from that due to the presence of two phases (phase leveltoxicity). They have observed that the diluents n-dodecanol and methyl oleate were only toxic at thephase level whereas paraffin oil was totally nontoxic toLactobacillus delbrueckii. They had also observed thatthe extractant tri-n-dodecylamine exhibited both phaselevel and molecular level toxicities.

The toxicity effect of extractants, TOA67 and Alamine336,19 and diluents, MIBK, octanol, paraffin liquid,67and oleyl alcohol,19 at molecular and phase levels aregiven in Tables 10 and 11, respectively. It is observedthat TOA exhibited symptoms of molecular level toxicityat 5% saturation level. In the case of phase level toxicity,they observed that TOA is highly toxic even at a lowphase ratio of 100:1 (aqueous-organic).67 At the phaselevel, paraffinic liquid was toxic and both octanol andMIBK were highly toxic. While the phase level toxicityof octanol was very high and its molecular level toxicitywas low. It can be revealed that paraffin liquid is themost suitable diluent for the simultaneous extractionof lactic acid during fermentation. However, paraffin

Table 8. Effect of NaCl on the Extraction of Lactic Acidwith Alamine 336 (20%, v/v) in Toluene at 25 Ca

lactic acid,g L-1

NaCl,g L-1 KD

lactic acid,g L-1

NaCl,g L-1 KD

40 0 0.71 40 5.0 0.5340 3.5 0.61

a Reproduced with permission from San-Martin et al.69 Copy-right 1992 John Wiley & Sons Ltd. on behalf of Society of ChemicalIndustry (SCI).

Aaq f Aorg

A + zB S Complexorg

RA ) [A*]x 2m + 1DAkmn[A*]m-1[B0]n (10)

Table 9. Rate Constants of the Lactic Acid-Alamine 336Reaction in Various Diluents

diluentrate

constant, s-1 diluentrate

constant, s-1

MIBK56 1.4 octanol53 24decanol58 0.2

5976 Ind. Eng. Chem. Res., Vol. 43, No. 19, 2004

liquid has a lower distribution coefficient than octanol;hence, octanol can be used for the reactive extractionof lactic acid from fermentation broth provided that thephase level toxicity is avoided by an immobilized cellsystem.67

It can be seen that adding soybean oil in immobilizedcells significantly reduces the toxicity.20 The solventaffected the cells through both the water-soluble portionand the immiscible portion of the solvent. While im-mobilization significantly protected the cells from theimmiscible solvent phase, the water-soluble part of thesolvent still caused toxicity to the microorganisms dueto diffusion of the solvent into the matrix. Addingsoybean oil to the -carrageenan matrix could trap thediffusing solvent molecules and therefore reduce thetoxic effect from the water-soluble portion of the sol-vent.20

Tik et al.25 obtained a maximum total lactic acidconcentration (2.5 times that without extraction) when15% Alamine 336 in oleyl alcohol together with im-mobilized cells with 15% sunflower oil was used. Co-immobilization with sunflower oil probably affected themetabolism of the microorganism. Fats and oils are usedas carbon sources, and they are broken down to glyceroland fatty acids. Fatty acids are used as the source ofadenosine triphosphate, while glycerol is converted topyruvate via glycolysis. Then, lactate is formed frompyruvate under anaerobic conditions.87 Therefore, lacticacid production increased with an increase in thesunflower oil concentration. The sunflower oil can alsoextract Alamine 336 that diffused into the gels andprevent the toxic effect of the solvent. These are the

reasons why sunflower oil was used in the extractivefermentation experiments.25

From the above discussion, it can be seen that, forlactic acid extraction, Alamine 336 in oleyl alcohol,which has the highest KD value, would serve as an idealextraction system unless the higher phase level toxicityof octanol is reduced by using an immobilized enzymesystem.

11. Process

Yabannavar and Wang21 suggested an efficient ex-tractive fermentation process for the production of lacticacid. To extract the lactic acid during fermentation, themedium from the fermentor was passed through amixer-settler and the aqueous phase was recycled. Themedium from the fermentor was mixed with the solvent(15% Alamine 336 in oleyl alcohol) in the mixer, andthe mixture was later separated into two phases in thesettler. The extractive fermentation was controlledthrough a pH controller. The controller monitored thepH decrease in the fermentor due to lactic acid forma-tion and, accordingly, activated (through on/off control)the inlet solvent and exit fluid pumps to initiate theextraction operation. Thus, by removal of the productduring fermentation, the pH and the product concentra-tion were maintained constant.21 Yabannavar andWang21 have given two processes for the regenerationof lactic acid from a loaded organic phase. Details ofthese are given later under the Backextraction of LacticAcid section.

Wasewar et al.53 studied reactive extraction of lacticacid in batch and semibatch modes using Alamine 336in diluents (MIBK, decanol, and octanol) and suggestedan efficient extractive fermentation process for theproduction of lactic acid. They extended the equilibriumand kinetics data for the in situ reactive extraction fromthe fermentation broth and developed a mathematicalmodel for the slurry phase reactor with glucose in thecontinuous aqueous phase, the amine dissolved in adiluent in the dispersed organic phase, and the im-mobilized cells as the solid phase. Comparison of semi-batch, batch, and plain fermentation without recoveryoperation clearly indicated the superiority of semibatchoperation. Comparison of the various modes showedthat the productivity of the semibatch mode yields anorder of magnitude higher productivity than the batchmode, and therefore this scheme fits in perfectly withthe definition of process intensification.88 A similarapproach was used by Gaidhani et al.89,90 for thehydrolysis of Penicillin G. Lactic acid extracted in theorganic phase can be backextracted with a strongervolatile amine like TMA in the aqueous phase. The TMAcan be stripped and recovered by absorption in waterand recycled to obtain a closed-loop system as shownby Wasewar et al.53 The process suggested is a sustain-able process because it does not consume any extrareagent and also does not produce a large waste streamlike in the conventional process.53 The various processesavailable in the literature have the following commoncomponents: (1) fermenter with reactive extraction, (2)regeneration and recycle of the reactive extractant bydifferent techniques, and (3) recovery of lactic acid.Inasmuch as the main difference is only in step 2 above,all of the processes can be depicted by a single flowsheetas shown in Figure 3. Step 2 is discussed individuallyfor the different techniques suggested in section 12.

Table 10. Molecular-Level Toxicity

diluent-extractant% cell growth

compared to control ref

saturated TOA 11.4 6775% saturated TOA 11.1 6720% saturated TOA 14.2 6710% saturated TOA 28.1 675% saturated TOA 72.6 672% saturated TOA 100 67100% MIBK 61.7 6750% MIBK 86.7 67100% octanol 83.4 67saturated with 15% Alamine 336 68.8 19saturated with 50% Alamine 336 55.6 19saturated with 100% Alamine 336 8.3 1950% Alamine 336 (immobilized cells) 55.6 1950% Alamine 336 (immobilized cells,

using soybean oil)72.2 19

100% Alamine 336 (immobilized cells) 2.8 19100% Alamine 336 (immobilized cells,

using soybean oil)66.7 19

Table 11. Phase-Level Toxicity

diluent-extractant% cell growth

compared to control ref

25:1 (Aq.-TOA) 6.7 6750:1 (Aq.-TOA) 6.5 67100:1 (Aq.-TOA) 5.6 671:1 (Aq.-paraffin liquid) 96.45 671:1 (Aq.-MIBK) 3.74 671:1 (Aq.-octanol) 12.46 67oleyl alcohol 96.7 1915% Alamine 336 in oleyl alcohol 41.7 1930% Alamine 336 in oleyl alcohol 0 1915% Alamine 336 in oleyl alcohol

(immobilized cells)73.3 19

30% Alamine 336 in oleyl alcohol(immobilized cells)

41.2 19

Ind. Eng. Chem. Res., Vol. 43, No. 19, 2004 5977

12. Backextraction of Lactic Acid

Tamada and King74 considered two approaches forregeneration through backextraction into an aqueousphase. These involve changes in the equilibrium rela-tionship through a swing of temperature and a swingof diluent composition. Yabannavar and Wang21 sug-gested two methods for recovery of lactic acid from aloaded solvent phase: using NaOH and using HCl. Theavailable regeneration methods for lactic acid from aloaded organic phase are described individually in thefollowing:

Using NaOH. In the first recovery method, Yaban-navar and Wang21 suggested the backextraction of lacticacid from a loaded organic phase (lactic acid + Alamine336 + oleyl alcohol) (Figure 3) with small volume of asodium hydroxide solution [1:10 (v/v) NaOH-solvent].NaOH in excess of stoichiometric amounts can be usedto ensure complete lactic acid recovery. Yabannavar andWang21 obtained 100% recovery of lactate. The resultanthigh product concentration is certainly desirable fromthe point of economic product recovery.

However, the acid is then present as sodium lactate.One must add an appropriate acid (e.g., sulfuric acid)to return it to the free acid form. This approach has thesame drawbacks as the classical calcium precipitationprocess for direct recovery from the aqueous feed. Bothsulfuric acid and NaOH are consumed, and a waste saltsludge is formed, which requires disposal.

Using HCl. In the second recovery method (Figure3) suggested by Yabannavar and Wang,21 concentratedHCl is used to essentially displace the lactic acid fromthe loaded organic phase (lactic acid + Alamine 336 +oleyl alcohol). In this method, undissociated lactic acidis obtained instead of lactic acid. More than stoichio-metric amounts of HCl were necessary to recover mostof the product from the solvent. The lactic acid recoveredthrough backextraction with HCl is in the undissociatedform. It is possible to regenerate the solvent by distillingoff the volatile HCl. Ricker et al.64 have detailed asimilar regeneration process where acetic acid wasremoved from the solvent by distillation. This methodhas the drawbacks that aqueous HCl is highly corrosiveand requires special material of construction (glasslined-graphite).

Using Distillation and Ammonia. Jung et al.55suggested the process (Figure 3) for extraction of lacticacid using tri-n-hexylamine in various solvents.The regeneration of the accumulated extract consistingof butanol-water-tri-n-hexylamine-lactic acid wasachieved by distillation of the light components butanoland water, followed by reextraction of the acid with aconcentrated solution of ammonia.55 As the end product,a highly concentrated solution of ammonium lactate isobtained. The lactic acid can be isolated from lactate,for instance, as a hydroxycarboxylic acid or as an esterby ion exchange91 or in situ esterification,57 respectively.

The salt solution is concentrated by evaporation andheated so as to decompose ammonium lactate, formingproduct lactic acid along with ammonia for recycle.However, ammonia lactate forms amides when heated.

Using TMA. Poole and King92 suggested a reactiveextraction process (Figure 3) in which a high molecularweight, organic-soluble amine in an appropriate organicdiluent is used as the forward extractant and anaqueous solution of a low molecular weight amine isused for backextraction.

To avoid consumption of chemicals and creation of asalt byproduct, the aqueous base, which is volatile,enables thermal decomposition of the acid-base com-plex in the aqueous backextract. The decompositionforms carboxylic acid as a product and free base as avapor that can be reabsorbed in water and recycled forreuse in backextraction.

The most obvious water-soluble, volatile base isammonia. However, ammonia and both primary andsecondary amines form amides when they are heatedin mixtures with carboxylic acids.93-95 The amides aresufficiently stable so that it is difficult to reverse theprocess and recover the amine. Hence, Poole and King92and Wasewar et al.54 employed TMA for backextractionof lactic acid from the loaded organic phase (lactic acid+ MIBK-octanol + Alamine 336). They found thatessentially 100% of the acid is backextracted into theaqueous phase at conditions in which there is at least1 mol of TMA for every equivalent weight of acid.

The studies on the thermal regeneration of TMAshowed that practically 100% of the TMA can beregenerated by employing a low pressure (200 mmHg)

Figure 3. Generalized flow sheet for fermentation of glucose to lactic acid coupled with semibatch reactive extraction and recovery oflactic acid-extractant.

5978 Ind. Eng. Chem. Res., Vol. 43, No. 19, 2004

coupled with heating to 100-120 C.54,95 In an actualindustrial unit, the thermal regeneration of off-gasescontaining water vapor and TMA can be first cooled ina falling-film type of condenser where most of the TMAwill be absorbed by the condensing water vapor.54 It iswell-known that when the direction of heat and masstransfer is the same (such as in this case), relativelyhigh mass-transfer coefficients are realized.96 Thus, afalling-film condenser cum absorber can yield goodrecovery of TMA-water vapors. Final polishing of theexhaust can be done in an additional falling-filmabsorber in order to maintain a low pressure drop. TMAis highly soluble in water under proper operatingconditions and a well-designed absorber; hence, negli-gible quantities of TMA are expected to escape.54

The organic phase, which is recycled to the fermentor,may contain residual dissolved TMA, which should beremoved in a stripper before the recycle because TMAcan affect the bioactivity of the enzyme.

Temperature-Swing Regeneration. In a temper-ature-swing extraction/regeneration scheme,74 the ex-traction is carried out at relatively low temperature,producing an acid-loaded organic extract and an aque-ous raffinate waste stream containing the unwantedfeed components. During regeneration, the extract iscontacted with a fresh aqueous stream at a highertemperature to produce an acid-laden aqueous productstream and an acid-free organic phase. The concentra-tion of the acid achievable in this stream depends onthe amount of change in the extraction equilibriumbetween temperatures and can be higher than that inthe original aqueous feed stream.18

Because of the lower enthalpy change, the extractionof lactic acid by Alamine 336 in MIBK and chloroformdoes not show as large a temperature effect.97 Hence,temperature-swing regeneration would be less effectivefor lactic acid.

Diluent-Swing Regeneration. Tamada and King97suggested the diluent-swing regeneration process (Fig-ure 3) for lactic acid. Baniel et al.15 also describedregeneration by backextraction following a change inthe diluent composition. In the diluent-swing process,extraction is carried out in a solvent composed of theamine and a diluent that promotes distribution of theacid in the organic phase. The composition of the acid-laden organic phase leaving the extractor is thenaltered, by either removal of the diluent or addition ofanother diluent, to produce a solvent system thatpromotes distribution of the acid to the aqueous phase.This altered organic phase is contacted with a freshaqueous stream in the regenerator to produce the acid-laden aqueous product and the acid-free solvent forrecycle to the extractor.97 Adjustment of the diluentcomposition can also occur before this solvent reentersthe extractor. This approach involving more than onediluent appears to be more complicated than the TMAapproach, where an easily removable volatile amine(TMA) is the only externally introduced component. Thisprocess has the disadvantage of diluting the extractstream and requiring distillation of large amounts ofsolvent (after the regeneration) to obtain the same shiftin the active/inert diluent ratio.

Gas-Antisolvent-Induced Regeneration. A draw-back to the diluent-swing regeneration15,74 is thatchanges in the extractant-phase composition generallyinvolve a distillation step to separate the active andinert diluents. To avoid this energy expense, a new

process is proposed by McMorris and Husson98 (Figure3) that will replace the inert liquid diluent with a gasantisolvent. Here, antisolvent is used to denote asubstance that has a low capacity to solubilize theextracted acid. In this process, the diluent compositionchange will be effected by pressurizing it with a gasantisolvent (e.g., propane). A benefit of this process overconventional recovery techniques is that the diluentcomponents can be easily separated (e.g., by a flashdistillation) without using a distillation step.98 Esti-mated energy requirements for a diluent-swing processinvolving the gaseous diluent, propane, were lower byat least a factor of 14 than those for a diluent-swingprocess involving the inert liquid diluent, dodecane.98

From the above discussion, it can be seen thatregeneration of lactic acid from the loaded organic phaseby a gas-antisolvent-induced method is the best suitablemethod because this process does not require any toxicmaterial like TMA and also the energy requirement islow because of the lack of a distillation step comparedto other processes.

13. Process Economics

The cost of the fermentation product depends on thefermentation process and recovery of the product. Inconventional processes, 50% of the cost of production iscontributed by the fermentation process and the other50% by the recovery and purification stages. Productioncosts of lactic acid can be reduced by increasing theproductivity and using the proper recovery method.There are a number of in situ recovery methods for lacticacid recovery (as mentioned earlier in the Introductionsec-tion). The advantages/disadvantages of various recoverymethods for lactic acid are summarized in Table 12.

It can be seen from Table 12 that reactive extractionis attractive for the recovery of lactic acid. Reactiveliquid-liquid extraction has the advantage that lacticacid can be removed easily from the fermentation broth.The extraction process if operated properly is self-adjusting, and therefore the expensive pH controlsystem used in the conventional process can be dis-pensed. Further, lactic acid can be reextracted and theextractant recycled to the fermentation process. Inaddition, as mentioned earlier, fermentation coupledwith reactive extraction has a relatively very highproductivity (approximately 25 times) compared to theplain fermentation, which reduces the fixed plant costfor a given production capacity. However, consideringenzyme stability and extractant toxicity, a biomembranereactor with enzyme immobilized in the pores of ahydrophilic membrane appears to be more attractive.This theme needs urgent attention.

14. Conclusion

It is important to have an efficient and sustainableprocess for the separation of lactic acid from thefermentation broth. Although commercial processes forlactic acid recovery are based on the classical methodof separation, the result of work on reactive extractionof lactic acid is promising. Extensive literature availableon the reactive extraction of lactic acid with respect toequilibria, kinetics, solvent toxicity, recovery, etc., isanalyzed. The effects of various parameters on thereactive extraction of lactic acid are given.

The main parameters for the selection of a diluent-extractant system for extraction are the distribution

Ind. Eng. Chem. Res., Vol. 43, No. 19, 2004 5979

coefficient and complexation constant, toxicity, andfeasibility for backextraction.

From the available study, it can be seen that Alamine336 in proper diluent (octanol and oleyl alcohol) is thebest extractant in terms of the distribution coefficient,toxicity, and feasibility for backextraction. For thediluent selection, oleyl alcohol is a better diluent thanoctanol. The solvent toxicity versus the microorganismcan be prevented by immobilization of cells with 15%sunflower oil.25

For the forward extraction process suggested byYabannavar and Wang,21 Wasewar et al.s work53 canbe used because, by removal of the product duringfermentation, the pH and the product concentrationwere maintained constant. For backextraction, the gas-antisolvent-induced method is the most suitable methodbecause this process does not require any toxic materiallike TMA and also the energy requirement is lowbecause of the lack of a distillation step compared toother processes. The process suggested is a sustainableprocess because it does not consume any extra reagentand also does not produce a large waste stream as inthe conventional process.

15. Scope and Directions for Future WorkAs discussed earlier most extractants have a very

good extraction capacity at lower pH of the media. Onthe other hand, most microbial strains available forconversion of glucose to lactic acid afford high activityat higher pH. This is the classical dilemma faced by theprocess developers. In view of this, there is an urgentneed to either develop extractants, which work at higherpH or strains and which yield good conversion to lacticacid at lower pH. In view of the rapid advances beingmade in developing tailor-made strains, the latter option

is likely to be more appropriate. Thus, future workshould focus on the development of new strains suitablefor operation at lower pH.

The growing demand of lactic acid draws attentionto the improvement of a conventional recovery processfor lactic acid production. Reactive extraction usingamine is an emerging prospective method for therecovery of lactic acid from fermentation broth. Eco-nomical evaluation data of various processes of lacticacid production and its recovery are not available.Therefore, it is necessary to focus on the economicalevaluation of various processes of lactic acid productionand its recovery for the economical comparison.

Nomenclature[A] ) lactic acid concentration (kmol m-3)[B] ) amine concentration in the organic phase (kmol m-3)[BHL] ) 1:1 lactic acid-Alamine complex concentration in

the organic phase (kmol m-3)DA ) diffusivity of solute A (lactic acid) in solvent (m2 s-1)[HL] ) lactic acid concentration (kmol m-3)KE1 ) 1:1 lactic acid-Alamine equilibrium complexation

constant (m3 kmol-1)KE2 ) 2:1 lactic acid-Alamine equilibrium complexation

constant [(m3 kmol-1)2]KE3 ) 3:1 lactic acid-Alamine equilibrium complexation

constant [(m3 kmol-1)3]KEn ) n:1 lactic acid-Alamine equilibrium complexation

constant [(m3 kmol-1)n]k1 ) first-order rate constant (s-1)KD ) distribution coefficientkmn ) rate constant for a reaction that is mth order in

species A and nth order in species B [kmol m-3 s-1 (m3kmol-1)m+n]

R ) gas constant in eq 12 (kJ mol-1 K-1)RA ) specific rate of extraction of lactic acid (kmol m-2 s-1)

Table 12. Advantages/Disadvantages of Various Recovery Methods for Lactic Acid

recovery method advantages/disadvantages

calcium hydroxide precipitation advantage: simple and reliable processdrawbacks: consumption of large quantities of reagents (H2SO4 and lime); huge amount

(ca. 2.5 tons) of waste per ton of lactic acid; disposal problem of waste;very poor sustainability

dialysis advantage: good potentialdrawbacks: membrane fouling; frequent cleaning is required; large dialysis unit as

compared to fermenter is required; technology is not mature enough forapplication on a large scale for bulk chemicals

electrodialysis advantage: simultaneous separation and concentration of lactic aciddrawbacks: higher power consumption; small amount of byproduct salt;

need for substantially more information for commercial useion exchange advantage: reliable technology

drawbacks: regeneration of ion-exchange resin and adjustment of feed pH to increasethe sorption efficiency requires a large amount of chemicals; waste streamgenerated creates treatment/disposal problem

distillation advantage: well-established/reliable technologydrawbacks: formation of high-boiling internal esters, dimers, and polymers of

lactic acid during distillationhollow fiber membrane extraction advantage: large interfacial area for mass transfer can be obtained in a compact unit

drawback: tendency to form emulsionliquid surfactant membrane extraction (LEM) advantage: large interfacial area for mass transfers in a compact unit

drawback: complexity of operation and swelling/instability of the LEMsupported liquid membranes advantage: large interfacial area for mass transfers in a compact unit

drawback: often suffers from membrane instabilitymembrane bioreactor advantage: continuous separation of products enhances the process

productivity; avoids toxicity due to extractant byimmobilization of biocatalyst in membrane

drawback: difficult cleaning and sterilizationreactive extraction advantage: closed-loop process; proper combination of extractant and diluent;

proper choice of backextractant yields high productivity;practically all data needed for commercial design are available

drawbacks: most extractants work efficiently at low pH, while most microbial strainsgive higher productivity at higher pH; toxicity of extractant toward the microbialstrain needs to be eliminated; development of new strains, which are robustand work at low pH, is required

5980 Ind. Eng. Chem. Res., Vol. 43, No. 19, 2004

RO ) initial rate of extraction of lactic acid (kmol m-2 s-1)T ) temperature (K)z ) loading ratio [kmol of lactic acid (kmol of amine)-1]H ) enthalpy change of the reaction in eq 12 (kJ mol-1)S ) entropy change of the reaction in eq 12 (kJ mol-1

K-1)

Subscripts

aq ) aqueous phaseorg ) organic phaseT ) total0 ) initial

Superscript

* ) equilibrium

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Received for review January 9, 2004Revised manuscript received May 17, 2004

Accepted June 21, 2004

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