Fermentation of Glucose to Lactic Acid Coupled with Reactive

Thus, for fermentation products to penetrate the organic chemicals industry, substantial improvements in the existing recovery technology are needed. ...
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Ind. Eng. Chem. Res. 2004, 43, 5969-5982

5969

REVIEWS Fermentation of Glucose to Lactic Acid Coupled with Reactive Extraction: A Review Kailas L. Wasewar,† Archis A. Yawalkar,‡ Jacob A. Moulijn,‡ and Vishwas G. Pangarkar*,† Mumbai University Institute of Chemical Technology, Matunga, Mumbai 400019, India, and Reactor 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 materials and new materials of specific uses such as controlled drug delivery or artificial prostheses draws attention to the need for improvement of conventional processes for lactic acid production. Reactive extraction with a specified extractant giving a higher distribution coefficient has been proposed as a promising technique for the recovery of lactic acid. A critical analysis of the available literature data has been made, and some general conclusions have been drawn. A suitable extractant-diluent system for lactic acid extraction on the basis of distribution coefficient, toxicity, and feasibility for backextraction is suggested. Also, methods for backextraction and recovery are suggested. 1. Introduction For the last 2-3 decades, because of the sharp increase in petroleum costs, there has been a resurgence of interest in large-volume production of fermentation chemicals, and the potential role of a new energyefficient fermentation technology is receiving growing attention. The current economic impact of fermentation chemicals, however, is still limited, in large part because of difficulties of product recovery. Thus, for fermentation products to penetrate the organic chemicals industry, substantial improvements in the existing recovery technology are needed. Lactic acid is a commodity chemical produced by fermentation and utilized in the food, chemical, and pharmaceutical fields. Lactic acid is an important chemical that can be converted to propylene glycol, acrylic polymers, and polyesters. Lactate esters derived from biolactic acid are being considered as alternative benign solvents.1 In particular, an interesting application is the use of lactic acid as a monomer for the synthesis of biodegradable homopolymers and copolymers.2,3 Lactic acid is a raw material for the production of biodegradable poly(lactic acid). A growing demand for biodegradable polymers, substitutes for both conventional plastic materials and new materials of specific uses such as controlled drug delivery or artificial prostheses, draws attention the need for improvement of conventional processes for lactic acid production.4 * To whom correspondence should be addressed. Tel.: +91-22-24145616. Fax: +91-22-24145614. E-mail: vgp@ udct.org, [email protected]. † Mumbai University Institute of Chemical Technology. ‡ Delft University of Technology.

The world market of lactic acid is growing every year. The level of production is around 350 millions kg year-1,5 and the worldwide growth is believed by some observers to be 12-15% year-1.6 In December 1994, market prices in the U.S. for both fermentation and synthetic food-grade 50 and 88% lactic acid were $0.71 and $1.15 lb-1 ($1.56-2.53 kg-1), respectively. Technical-grade 88% lactic acid was quoted at $1.12 lb-1 ($2.47 kg-1).7 In April 2003, market prices in the U.S. for 88% foodgrade and technical-grade lactic acid were $0.77 and $0.7 lb-1, respectively. The 50% solution for grade lactic acid was $0.59 lb-1.8 These prices were 50% lower than the prices of year 1994, illustrating the economics of scale based on the increasing use of lactic acid. Recovery of lactic acid from aqueous solutions is a growing requirement in fermentation-based industries and so is recovery from waste streams. Lactic acid can be produced by the fermentation of biomass. For the production of lactic acid, the pH is very important and must be maintained between 5.5 and 6.5. However, during fermentation, the accumulation of lactic acid decreases the pH of the fermentation broth and the activity of the lactic acid producing bacteria decreases. Hence, the lactic acid accumulation inhibits the product formation. Also, if levels of free lactic acid reach 1-2 wt % of total combined lactic acid, then the bacteria are likely to die.9,10 The traditional recovery process of lactic acid from fermentation broth is quite complicated. Isolation of this acid from dilute solution or fermentation broths is an economic problem because the vaporization of water consumes much energy and a direct upgrading of the dilute solution by evaporation is inefficient. Lactic acid is nonvolatile, and hence distillation is not useful. In conventional processes, lactic acid has been recovered from the fermentation broth by precipitation of calcium

10.1021/ie049963n CCC: $27.50 © 2004 American Chemical Society Published on Web 07/31/2004

5970 Ind. Eng. Chem. Res., Vol. 43, No. 19, 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 sulfuric acid. The dilute lactic acid product is then sequentially purified using activated carbon, evaporation, and crystallization. These separation and final purification stages account for up to 50% of the production costs.11,12 Thus, this method of recovery is expensive and unfriendly to the environment because it consumes lime and sulfuric acid and also produces a large quantity of calcium sulfate sludge as solid waste.13 Because of the detrimental effect of low pH, reactor productivities are low and the products are obtained in a dilute form. The effects of end-product inhibition can be reduced by in situ removal of lactic acid from fermentation broth by several methods. A number of processes for lactic acid recovery from fermentation broth without precipitation have been studied and reported in the literature: solvent extraction,14-30 membrane bioreactor,31-33 liquid surfactant membrane extraction,34 adsorption,35-39 direct distillation,40 electrodialysis,41-46 reverse osmosis,47 anion exchange,48-50 etc. Electrodialysis and dialysis have the problem of membrane fouling, which requires frequent cleaning of the dialyzer. Moreover, large-volume dialysis units, even greater than the volume of the fermentor vessel, would be required in a commercial-scale unit.9 Electrodialysis gives a higher extent of lactic acid separation but with increased power and energy consumption.9 Also, large amounts of byproduct salts from the ion-exchange regeneration are formed. Adsorption or the ion-exchange process requires regeneration of an ion-exchange resin and adjustment of the feed pH to increase the sorption efficiency, requiring large amounts of chemicals.46 During direct distillation, high-boiling internal esters as dimers and polymers can be formed.40 In the extraction of lactic acid from fermentation broth with microporous hollow fiber membranes, there is a tendency to form an emulsion.33 Liquid surfactant membrane extraction exhibits a high complexity of operation due to swelling of the membranes in liquid surfactants.50 Supported liquid membranes often suffer from membrane instability.50 Reactive extraction with a specified extractant giving a higher distribution coefficient has been proposed as a promising technique for the recovery of carboxylic and hydroxycarboxylic acids.14,51,52 Reactive liquid-liquid extraction has the advantage that lactic acid can be removed easily from the fermentation broth, preventing lowering of the pH. Further, lactic acid can be reextracted and the extractant recycled to the fermentation process.53,54 A large number of literature studies are available on the reactive extraction of lactic acid. Reactive extraction strongly depends on various parameters such as the distribution coefficient, degree of extraction, loading ratio, complexation equilibrium constant, types of complexes (1:1, 2:1, etc.), rate constant of lactic acid-amine reaction, properties of the solvent (extractant and diluent), type of solvent, temperature, pH, acid concentration, salt present in the acid, water coextraction, toxicity, feasibility of backextraction, and solvent for backextraction. The results of these studies of the above parameters are available in a scattered form. In the present work, an attempt is made to combine the

available data on the reactive extraction of lactic acid and to discuss the same in a concise manner. A critical analysis of the available literature data has been made, and some general conclusions concerning the above-mentioned parameters have been drawn. 2. Types of Extractants A good starting point for developing a new extractive recovery process for lactic acid should be the identification of novel, more powerful extractants. In the reactive extraction of lactic acid, the extraction system must fulfill two basic requirements: a high distribution coefficient (KD)

KD ) [HL]org/[HL]aq

(1)

and a high selectivity for lactic acid. Further requirements of an extractant or a system of extractants are55 (i) low viscosity, (ii) higher density difference between the extractant and raffinate, (iii) a medium interfacial tension, (iv) thermal stability, (v) low enthalpy of vaporization, (vi) low melting points, (vii) no reaction between the extractant and raffinate, (viii) low solubility of the extractant in the raffinate, (ix) low toxicity and good biological degradability, and (x) low price and good availability. Kertes and King17 categorized the extractant into three major types: (I) conventional oxygen-bearing hydrocarbon extractants [methyl isobutyl ketone (MIBK), octanol, decanol, etc.], (II) phosphorus-bonded oxygenbearing extractants (tributyl phosphate, etc.), and (III) high molecular weight aliphatic amines (Aliquat, Alamine, etc.). The first two categories are nonreactive extractants and involve the solvation of the acid by donor bonds, which are to be distinguished from strong covalent bonds and from ionic interactions. In category III, a chemical reaction is involved. The distinction between the first two categories is based on the strength of the solvation bonds and the specificity of solvation.17 The conventional extractants, such as ketones, ethers, and alcohols, are not able to fulfill the basic requirements often because of their low distribution coefficients. The values of KD of lactic acid in various extractants are given in Table 1. It can be seen that the distribution coefficient of lactic acid is low (25%) of amine in diluent, a third emulsion phase was observed at the interface between the aqueous and organic phases.62 Hence, these authors suggested the use of 10-20% Alamine 336 in diluent. 3. Lactic Acid-Amine (Tertiary) Complex In the previous section, it was found that tertiary amine, Alamine 336, is the best suitable extractant for reactive extraction of lactic acid, and hence in this section only the lactic acid-amine complex is discussed. The fundamental difference between oxygen- and nitrogen-bearing basic extractants in the extraction of acids originates from the basic behavior of the acid proton during the transfer from an aqueous to an organic solution. In the systems with oxygen-bearing solvents, whether carbon, phosphorus, or sulfur is bound, the acid strength in the aqueous solution and the hydrogen bond in the organic solution determine the

5972 Ind. Eng. Chem. Res., Vol. 43, No. 19, 2004 Table 2. Distribution Coefficients for Lactic Acid in Various Solvent Mixtures-Water Systems extractant

diluent

KD

ref

15% Alamine 336 30% Alamine 336 50% Alamine 336 20% Alamine 336 30% Alamine 336 40% Alamine 336 20% Alamine 336 30% Alamine 336 40% Alamine 336 10% Alamine 336 20% Alamine 336 30% Alamine 336 50% Aliquat 336 25% Aliquat 336 50% Aliquat 336 50% Alamine tri-n-hexylamine (12.2 alcohol-amine molar ratio) tri-n-hexylamine (12.2 alcohol-amine molar ratio) tri-n-hexylamine (12.2 alcohol-amine molar ratio) diethylbutylamine (0.97 mol L-1) tributylamine (0.97 mol L-1) triamylamine (0.97 mol L-1) TOA (0.97 mol L-1) Alamine (0.4 mol L-1) Alamine (0.8 mol L-1) 50% di-n-hexylamine 50% di-n-octylamine 50% di-n-decylamine 50% tri-n-pentylamine 50% tri-n-hexylamine 50% tri-n-octylamine 50% tri-n-decylamine 50% Alamine 336 50% TOA 30% TOA 90% TOA 90% TOA TBP (3 mol dm-3) TBP (3 mol dm-3) + n-octylamine (0.3 mol dm-3) TBP (3 mol dm-3) + di-n-hexylamine (0.3 mol dm-3) TBP (3 mol dm-3) + TOA (0.3 mol dm-3) TBP (3 mol dm-3) + triisooctylamine (0.3 mol dm-3) TBP (3 mol dm-3) + triethylhexylamine (0.3 mol dm-3) TBP (3 mol dm-3) + TOA (0.2 mol dm-3) TBP (3 mol/dm3) + TOA (0.3 mol dm-3) TBP (3 mol dm-3) + TOA (0.3 mol dm-3) TBP (3 mol dm-3) + TOA (0.3 mol dm-3) TBP (3 mol dm-3) + TOA (0.3 mol dm-3)

oleyl alcohol oleyl alcohol oleyl alcohol MIBK MIBK MIBK decanol decanol decanol octanol octanol octanol kerosene kerosene 2-octanol 2-octanol 1-butanol 2-butanol isobutyl alcohol chloroform chloroform chloroform chloroform toluene toluene oleyl alcohol oleyl alcohol oleyl alcohol oleyl alcohol oleyl alcohol oleyl alcohol oleyl alcohol oleyl alcohol MIBK octanol octanol paraffin liquid hexane hexane hexane hexane hexane hexane hexane butyl acetate toluene chlorobenzene 1-decanol

3 4.5 6.5 0.72 2.68 4.24 12.57 16.44 23.37 15.35 19.69 25.95 0.90 0.20 0.78 2.50 22.1 12.5 23.6 1.8 1.4 2.7 4.5 0.83 2.06 0.757 11.1 7.76 0.72 2.94 1.90 1.66 2.62 3.75 0.90 1.2 0.4 0.75 0.17 0.51 3.4 1.5 0.78 2.4 2.8 2.8 3.0 2.9

68 68 68 56 56 56 58 58 58 53 53 53 62 62 62 62 55 55 55 66 66 66 66 69 69 61 61 61 61 61 61 61 61 67 67 67 67 70 70 70 70 70 70 70 70 70 70 70

extractability. On the other hand, the acid extracted into an amine-containing organic phase is no longer to be regarded as an acid but as an ammonium salt. It is thus the extent of ion-pair association between the alkylammonium cation and the acid radical that determines the extractability or, more precisely, the stability of the organic-phase species.17 Thus, the extraction process is based on an acid-basetype reaction between the amine B and the lactic acid HL KE1

HLaq + Borg 798 BHLorg KE )

[BHL]org [B]org[HL]aq

of a 1:1 complex.17,56,58,69,71 Though the exact nature of the chemistry involved in the uptake of extra acid is not known and despite the obvious nonideality of the organic phase under these conditions, distribution data can be interpreted in terms of simple mass action equations of the type17 KEn

nHLaq + BHLorg 798 BHL(HL)n,org KEn )

(2) (3)

where KE is the equilibrium complexation constant. Generally, the simple stoichiometric reaction (eq 2) is not suitable for describing the formation of a complex of acid and amine molecules because the organic phase extracts more acid than would be expected on the basis

[BHL(HL)n]org [BHL]org[HL]aqn

(4) (5)

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

z)

[HL]org [B]T,org

)

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

(6)

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

Ind. Eng. Chem. Res., Vol. 43, No. 19, 2004 5973 Table 3. Equilibrium Complexation Constants of Lactic Acid-Amine in Various Solvent Mixture-Water Systems

Figure 1. n:1 lactic acid-amine complex structure: (a) 1:1; (b) 2:1; (c) 3:1.

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

z ) KEn[HL]aqn n-z

(7)

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 common, and its structure is shown in Figure 1a. The formation of 2:1 and 3:1 lactic acid-amine complexes depends on the lactic acid concentration in the aqueous phase, and the ratio of 1:1 to 2:1 complex formation is diluent dependent.18 At higher concentrations of lactic acid, the 2:2 and 3:1 complexes can be formed.22,56,58 This overloading phenomenon results from a second lactic acid molecule hydrogen bonding to the lactic acid that is already involved in the 1:1 complex (Figure 1b). A third lactic acid molecule can then hydrogen bond to the second one in the same way, enabling loadings above two, and the 3:1 complex is shown in Figure 1c. Different diluents solvate the various complexes and the amine to different extents, thereby changing the activity coefficients. Generally, the greater the ionizing acidity of the acid, as measured by pKa, the more it is extracted. The strength of solvation of the complex by the diluent decreases in the following order:18 alcohol (e.g., 2-ethyl-1-hexanol) > nitrobenzene > proton-donating halogenated hydrocarbon (e.g., methylene chloride, chloroform, and 1,2-dichloroethane) > ketone (e.g., MIBK, diisobutyl ketone, and 2-heptanone) > halogenated aromatic (e.g., dichlorobenzene and chlorobenzene) > benzene > alkyl aromatic (e.g., toluene and xylene) > aliphatic hydrocarbon (e.g., hexane, heptane, and octane). Juang and Huang27 also observed the formation of three complexes of lactic acid with TOA. The values of

extractant

diluent

log KE1

log KE2

Alamine 336 Alamine 336 Alamine 336 Alamine 336 Alamine 336 Alamine 336 Alamine 336 TOA

chloroform xylene toluene toluene MIBK decanol octanol

2.57 -0.11 0.26 0.22 1.01 1.66 1.87 0.12

-0.45 -0.02 0.35 0.19 1.00 1.26 1.04 -1.09

log KE3 -1.29 -0.9 -1.01

-0.02

ref 18 72 71 69 56 58 53,73 27

the equilibrium complexation constants of a lactic acidamine complex in various diluents are shown in Table 3. In many studies, the complex 3:1 is not favored because the concentration of lactic acid in the organic phase is not high enough. This situation (because there is low concentration, carbon-bonded oxygen donor active diluents > phosphorus-bonded oxygen donor active diluents. Tamada and King74 performed studies to compare the coextraction of water, which accompanies the extraction of various other acids by Alamine 336 in chloroform, MIBK, and various alcohols. Monocarboxylic acids carry less water with them than dicarboxylic acids, which may reflect the tendency of coextracted water molecules to associate with the carboxylate group.74 Tamada and King74 found that, for the extraction of lactic acid by Alamine 336 in chloroform and MIBK, water coextraction increases with increasing temperature. In general, selectivity of the acid over water in the extraction by amine extractants is high relative to the results with conventional solvents. The water carried into the extract would be minimal compared to the amount of water used in an aqueous backextraction, and therefore 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 on the extraction of lactic acid, San-Martin et al.69 carried out several experiments to determine the distribution equilibrium of lactic acid. Their results indicated that the extraction of lactic acid with Alamine 336 dissolved in toluene is not affected by lactose. Variations of the

5976 Ind. Eng. Chem. Res., Vol. 43, No. 19, 2004 Table 8. Effect of NaCl on the Extraction of Lactic Acid with Alamine 336 (20%, v/v) in Toluene at 25 °Ca lactic acid, g L-1

NaCl, g L-1

KD

40 40

0 3.5

0.71 0.61

lactic acid, g L-1

NaCl, g L-1

KD

diluent

rate constant, s-1

40

5.0

0.53

MIBK56 decanol58

1.4 0.2

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

distribution coefficient of lactic acid for various sodium chloride concentrations in the aqueous phase are given in Table 8. It can be seen that if sodium chloride is present, less lactic acid is extracted by the organic phase. This was explained by San-Martin et al.69 by assuming that chlorine from sodium chloride and H+ ion from lactic acid yield hydrochloric acid, which is extracted by the amine. This may be due to a stronger acid like HCl competing for the reaction with the amine. They also found that the chloride extraction does not take place in the absence of lactic acid. 9. Kinetics Wasewar et al.53,56,58 studied the kinetics of reactive extraction of lactic acid using Alamine 336 in various diluents (MIBK, decanol, and octanol). They used the theory of extraction accompanied by a chemical reaction. Doraiswamy and Sharma81 have given an exhaustive discussion on the theory of extraction accompanied by a chemical reaction. Four regimes of extraction accompanied by reaction (very slow, slow, fast, and instantaneous) have been identified depending upon the physicochemical and hydrodynamic parameters. When the reaction is reversible, the solute has a finite equilibrium concentration in the bulk and the driving force needs to be modified by incorporating the equilibrium concentration. The extraction involves partitioning of the solute available in the aqueous phase to the organic phase.

Aaq f Aorg The solute A partitioned in the organic phase combines with the organic reactant (amine), B, according to

A + zB S Complexorg Using the guidelines given by Doraiswamy and Sharma,81 Wasewar et al.53,56,58 found that in a stirred cell the system belongs to regime 3, extraction accompanied by a fast general order chemical reaction occurring in the diffusion film; the expression for regime 3 is

xm 2+ 1D k

RA ) [A*]

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

m-1 [B0]n A mn[A*]

(10)

The reaction was found to be zero-order in Alamine 336 and first-order in lactic acid. The rate constants for the lactic acid-Alamine reaction in various diluents are given in Table 9. Table 9 indicates that octanol is a better solvent than the other two solvents based on kinetic considerations. Wasewar et al.54 studied the kinetics for the backextraction of lactic acid from a loaded organic phase (lactic acid + Alamine + octanol) using aqueous trimethylamine (TMA). The theory of extraction accom-

diluent

rate constant, s-1

octanol53

24

panied by chemical reaction was used to obtain the kinetics. The reaction between lactic acid and aqueous TMA in a stirred cell falls in regime 3, extraction accompanied by a fast chemical reaction occurring in the diffusion film. The reaction was found to be zeroorder in TMA and first-order in lactic acid with a rate constant of 16.67 s-1. 10. Toxicity The presence of an organic solvent can give rise to a series of physical microbial and biochemical effects on the catalytic activity of the microorganisms. Toxicity of the organic solvent and extractant to microbes is the critical problem in extractive fermentation. The degree of toxicity depends on the combination of microbe and extractant solution used. Bar and Gainer78 attempted to develop extractive fermentations for lactic, citric, and acetic acids and encountered problems of solvent toxicity and poor extraction. Brink and Tramper82 reported that the least toxicity is expected from solvents of low polarity in combination with high solvent molecular weight. Avoidance of direct contact of the organism with the organic, amine-bearing phase can substantially reduce toxic effects. To reduce the solvent toxicity, several investigators have used membranes to prevent direct contact of the solvent with the cell containing broth.83-85 Immobilization is another method to protect the cells by reducing the contact of the immiscible solvent with the microbes. Matsumura and Markl83 attempted to make a Porapack Q barrier to solvent molecules beneath the surface of gel beads as a protection against octanol dissolved in the medium. A calcium alginate immobilized gel system, with entrapped vegetable oil, has been reported to provide protection from octanol, benzene, phenol, and toluene.86 With regard to solvent toxicity, Bar and Gainer78 have differentiated the toxicity of the solvent due to the soluble portion of the solvent (molecular level toxicity) from that due to the presence of two phases (phase level toxicity). They have observed that the diluents ndodecanol and methyl oleate were only toxic at the phase level whereas paraffin oil was totally nontoxic to Lactobacillus delbrueckii. They had also observed that the extractant tri-n-dodecylamine exhibited both phase level and molecular level toxicities. The toxicity effect of extractants, TOA67 and Alamine 336,19 and diluents, MIBK, octanol, paraffin liquid,67 and oleyl alcohol,19 at molecular and phase levels are given in Tables 10 and 11, respectively. It is observed that TOA exhibited symptoms of molecular level toxicity at 5% saturation level. In the case of phase level toxicity, they observed that TOA is highly toxic even at a low phase ratio of 100:1 (aqueous-organic).67 At the phase level, paraffinic liquid was toxic and both octanol and MIBK were highly toxic. While the phase level toxicity of octanol was very high and its molecular level toxicity was low. It can be revealed that paraffin liquid is the most suitable diluent for the simultaneous extraction of lactic acid during fermentation. However, paraffin

Ind. Eng. Chem. Res., Vol. 43, No. 19, 2004 5977 Table 10. Molecular-Level Toxicity % cell growth compared to control ref

diluent-extractant saturated TOA 75% saturated TOA 20% saturated TOA 10% saturated TOA 5% saturated TOA 2% saturated TOA 100% MIBK 50% MIBK 100% octanol saturated with 15% Alamine 336 saturated with 50% Alamine 336 saturated with 100% Alamine 336 50% Alamine 336 (immobilized cells) 50% Alamine 336 (immobilized cells, using soybean oil) 100% Alamine 336 (immobilized cells) 100% Alamine 336 (immobilized cells, using soybean oil)

11.4 11.1 14.2 28.1 72.6 100 61.7 86.7 83.4 68.8 55.6 8.3 55.6 72.2

67 67 67 67 67 67 67 67 67 19 19 19 19 19

2.8 66.7

19 19

Table 11. Phase-Level Toxicity diluent-extractant 25:1 (Aq.-TOA) 50:1 (Aq.-TOA) 100:1 (Aq.-TOA) 1:1 (Aq.-paraffin liquid) 1:1 (Aq.-MIBK) 1:1 (Aq.-octanol) oleyl alcohol 15% Alamine 336 in oleyl alcohol 30% Alamine 336 in oleyl alcohol 15% Alamine 336 in oleyl alcohol (immobilized cells) 30% Alamine 336 in oleyl alcohol (immobilized cells)

% cell growth compared to control

ref

6.7 6.5 5.6 96.45 3.74 12.46 96.7 41.7 0 73.3

67 67 67 67 67 67 19 19 19 19

41.2

19

liquid has a lower distribution coefficient than octanol; hence, octanol can be used for the reactive extraction of lactic acid from fermentation broth provided that the phase level toxicity is avoided by an immobilized cell system.67 It can be seen that adding soybean oil in immobilized cells significantly reduces the toxicity.20 The solvent affected the cells through both the water-soluble portion and the immiscible portion of the solvent. While immobilization significantly protected the cells from the immiscible solvent phase, the water-soluble part of the solvent still caused toxicity to the microorganisms due to diffusion of the solvent into the matrix. Adding soybean oil to the κ-carrageenan matrix could trap the diffusing solvent molecules and therefore reduce the toxic effect from the water-soluble portion of the solvent.20 Tik et al.25 obtained a maximum total lactic acid concentration (2.5 times that without extraction) when 15% Alamine 336 in oleyl alcohol together with immobilized cells with 15% sunflower oil was used. Coimmobilization with sunflower oil probably affected the metabolism of the microorganism. Fats and oils are used as carbon sources, and they are broken down to glycerol and fatty acids. Fatty acids are used as the source of adenosine triphosphate, while glycerol is converted to pyruvate via glycolysis. Then, lactate is formed from pyruvate under anaerobic conditions.87 Therefore, lactic acid production increased with an increase in the sunflower oil concentration. The sunflower oil can also extract Alamine 336 that diffused into the gels and prevent the toxic effect of the solvent. These are the

reasons why sunflower oil was used in the extractive fermentation experiments.25 From the above discussion, it can be seen that, for lactic acid extraction, Alamine 336 in oleyl alcohol, which has the highest KD value, would serve as an ideal extraction system unless the higher phase level toxicity of octanol is reduced by using an immobilized enzyme system. 11. Process Yabannavar and Wang21 suggested an efficient extractive fermentation process for the production of lactic acid. To extract the lactic acid during fermentation, the medium from the fermentor was passed through a mixer-settler and the aqueous phase was recycled. The medium from the fermentor was mixed with the solvent (15% Alamine 336 in oleyl alcohol) in the mixer, and the mixture was later separated into two phases in the settler. The extractive fermentation was controlled through a pH controller. The controller monitored the pH decrease in the fermentor due to lactic acid formation and, accordingly, activated (through on/off control) the inlet solvent and exit fluid pumps to initiate the extraction operation. Thus, by removal of the product during fermentation, the pH and the product concentration were maintained constant.21 Yabannavar and Wang21 have given two processes for the regeneration of lactic acid from a loaded organic phase. Details of these are given later under the Backextraction of Lactic Acid section. Wasewar et al.53 studied reactive extraction of lactic acid in batch and semibatch modes using Alamine 336 in diluents (MIBK, decanol, and octanol) and suggested an efficient extractive fermentation process for the production of lactic acid. They extended the equilibrium and kinetics data for the in situ reactive extraction from the fermentation broth and developed a mathematical model for the slurry phase reactor with glucose in the continuous aqueous phase, the amine dissolved in a diluent in the dispersed organic phase, and the immobilized cells as the solid phase. Comparison of semibatch, batch, and plain fermentation without recovery operation clearly indicated the superiority of semibatch operation. Comparison of the various modes showed that the productivity of the semibatch mode yields an order of magnitude higher productivity than the batch mode, and therefore this scheme fits in perfectly with the definition of process intensification.88 A similar approach was used by Gaidhani et al.89,90 for the hydrolysis of Penicillin G. Lactic acid extracted in the organic phase can be backextracted with a stronger volatile amine like TMA in the aqueous phase. The TMA can be stripped and recovered by absorption in water and recycled to obtain a closed-loop system as shown by Wasewar et al.53 The process suggested is a sustainable process because it does not consume any extra reagent and also does not produce a large waste stream like in the conventional process.53 The various processes available in the literature have the following common components: (1) fermenter with reactive extraction, (2) regeneration and recycle of the reactive extractant by different 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 flowsheet as shown in Figure 3. Step 2 is discussed individually for the different techniques suggested in section 12.

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

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

12. Backextraction of Lactic Acid Tamada and King74 considered two approaches for regeneration 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 Wang21 suggested two methods for recovery of lactic acid from a loaded solvent phase: using NaOH and using HCl. The available regeneration methods for lactic acid from a loaded organic phase are described individually in the following: Using NaOH. In the first recovery method, Yabannavar and Wang21 suggested the backextraction of lactic acid from a loaded organic phase (lactic acid + Alamine 336 + oleyl alcohol) (Figure 3) with small volume 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 Wang21 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 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 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 sludge is formed, which requires disposal. Using HCl. In the second recovery method (Figure 3) suggested by Yabannavar and Wang,21 concentrated HCl is used to essentially displace the lactic acid from the loaded organic phase (lactic acid + Alamine 336 + oleyl alcohol). In this method, undissociated lactic acid is obtained instead of lactic acid. 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 by distilling off the volatile HCl. Ricker et al.64 have detailed a similar regeneration process where acetic acid was removed from the solvent by distillation. This method has the drawbacks that aqueous HCl is highly corrosive and requires special material of construction (glass lined-graphite).

Using Distillation and Ammonia. Jung et al.55 suggested the process (Figure 3) for extraction of lactic acid using tri-n-hexylamine in various solvents. The regeneration of the accumulated extract consisting of butanol-water-tri-n-hexylamine-lactic acid was achieved by distillation of the light components butanol and water, followed by reextraction of the acid with a concentrated solution of ammonia.55 As the end product, a highly concentrated solution of ammonium lactate is obtained. The lactic acid can be isolated from lactate, for instance, as a hydroxycarboxylic acid or as an ester by ion exchange91 or in situ esterification,57 respectively. The salt solution is concentrated by evaporation and heated so as to decompose ammonium lactate, forming product lactic acid along with ammonia for recycle. However, ammonia lactate forms amides when heated. Using TMA. Poole and King92 suggested a reactive extraction process (Figure 3) in which a high molecular weight, organic-soluble amine in an appropriate organic diluent is used as the forward extractant and an aqueous solution of a low molecular weight amine is used for backextraction. To avoid consumption of chemicals and creation of a salt byproduct, the aqueous base, which is volatile, enables thermal decomposition of the acid-base complex in the aqueous backextract. The decomposition forms carboxylic acid as a product and free base 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 amines form amides when they are heated in mixtures with carboxylic acids.93-95 The amides are sufficiently stable so that it is difficult to reverse the process and recover the amine. Hence, Poole and King92 and Wasewar et al.54 employed TMA for backextraction of lactic acid from the loaded organic phase (lactic acid + MIBK-octanol + Alamine 336). They found that essentially 100% of the acid is backextracted into the aqueous phase at conditions in which there is at least 1 mol of TMA for every equivalent weight of acid. The studies on the thermal regeneration of TMA showed that practically 100% of the TMA can be regenerated by employing a low pressure (200 mmHg)

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

coupled with heating to 100-120 °C.54,95 In an actual industrial unit, the thermal regeneration of off-gases containing water vapor and TMA can be first cooled in a falling-film type of condenser where most of the TMA will be absorbed by the condensing water vapor.54 It is well-known that when the direction of heat and mass transfer is the same (such as in this case), relatively high mass-transfer coefficients are realized.96 Thus, a falling-film condenser cum absorber can yield good recovery of TMA-water vapors. Final polishing of the exhaust can be done in an additional falling-film absorber in order to maintain a low pressure drop. TMA is highly soluble in water under proper operating conditions and a well-designed absorber; hence, negligible quantities of TMA are expected to escape.54 The organic phase, which is recycled to the fermentor, may contain residual dissolved TMA, which should be removed in a stripper before the recycle because TMA can affect the bioactivity of the enzyme. Temperature-Swing Regeneration. In a temperature-swing extraction/regeneration scheme,74 the extraction is carried out at relatively low temperature, producing an acid-loaded organic extract and an aqueous raffinate waste stream containing the unwanted feed components. During regeneration, the extract is contacted with a fresh aqueous stream at a higher temperature to produce an acid-laden aqueous product stream and an acid-free organic phase. The concentration 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.18 Because of the lower enthalpy change, the extraction of lactic acid by Alamine 336 in MIBK and chloroform does not show as large a temperature effect.97 Hence, temperature-swing regeneration would be less effective for lactic acid. Diluent-Swing Regeneration. Tamada and King97 suggested the diluent-swing regeneration process (Figure 3) for lactic acid. Baniel et al.15 also described regeneration by backextraction following a change in the diluent composition. In the diluent-swing process, extraction is carried out in a solvent composed of the amine and a diluent that promotes distribution of the acid in the organic phase. The composition of the acidladen organic phase leaving the extractor is then altered, by either removal of the diluent or 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 aqueous stream in the regenerator to produce the acidladen aqueous product and the acid-free solvent for recycle to the extractor.97 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 distillation of large amounts of solvent (after the regeneration) to obtain the same shift in the active/inert diluent ratio. Gas-Antisolvent-Induced Regeneration. A drawback to the diluent-swing regeneration15,74 is that changes in the extractant-phase composition generally involve a distillation step to separate the active and inert diluents. To avoid this energy expense, a new

process is proposed by McMorris and Husson98 (Figure 3) that will replace the inert liquid diluent with a gas antisolvent. Here, antisolvent is used to denote a substance that has a low capacity to solubilize the extracted acid. In this process, the diluent composition change will be effected by pressurizing it with a gas antisolvent (e.g., propane). A benefit of this process over conventional recovery techniques is that the diluent components can be easily separated (e.g., by a flash distillation) without using a distillation step.98 Estimated energy requirements for a diluent-swing process involving the gaseous diluent, propane, were lower by at least a factor of 14 than those for a diluent-swing process involving the inert liquid diluent, dodecane.98 From the above discussion, it can be seen that regeneration of lactic acid from the loaded organic phase by a gas-antisolvent-induced method is the best suitable method because this process does not require any toxic material like TMA and also the energy requirement is low because of the lack of a distillation step compared to other processes. 13. Process Economics The cost of the fermentation product depends on the fermentation process and recovery of the product. In conventional processes, 50% of the cost of production is contributed by the fermentation process and the other 50% by the recovery and purification stages. Production costs of lactic acid can be reduced by increasing the productivity and using the proper recovery method. There are a number of in situ recovery methods for lactic acid recovery (as mentioned earlier in the Introduction section). The advantages/disadvantages of various recovery methods for lactic acid are summarized in Table 12. It can be seen from Table 12 that reactive extraction is attractive for the recovery of lactic acid. Reactive liquid-liquid extraction has the advantage that lactic acid can be removed easily from the fermentation broth. The extraction process if operated properly is selfadjusting, and therefore the expensive pH control system used in the conventional process can be dispensed. Further, lactic acid can be reextracted and the extractant recycled to the fermentation process. In addition, as mentioned earlier, fermentation coupled with reactive extraction has a relatively very high productivity (approximately 25 times) compared to the plain fermentation, which reduces the fixed plant cost for a given production capacity. However, considering enzyme stability and extractant toxicity, a biomembrane reactor with enzyme immobilized in the pores of a hydrophilic membrane appears to be more attractive. This theme needs urgent attention. 14. Conclusion It is important to have an efficient and sustainable process for the separation of lactic acid from the fermentation broth. Although commercial processes for lactic acid recovery are based on the classical method of separation, the result of work on reactive extraction of lactic acid is promising. Extensive literature available on the reactive extraction of lactic acid with respect to equilibria, kinetics, solvent toxicity, recovery, etc., is analyzed. The effects of various parameters on the reactive extraction of lactic acid are given. The main parameters for the selection of a diluentextractant system for extraction are the distribution

5980 Ind. Eng. Chem. Res., Vol. 43, No. 19, 2004 Table 12. Advantages/Disadvantages of Various Recovery Methods for Lactic Acid recovery method calcium hydroxide precipitation

dialysis

electrodialysis ion exchange

distillation hollow fiber membrane extraction liquid surfactant membrane extraction (LEM) supported liquid membranes membrane bioreactor

reactive extraction

advantages/disadvantages advantage: simple and reliable process drawbacks: 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 advantage: good potential drawbacks: membrane fouling; frequent cleaning is required; large dialysis unit as compared to fermenter is required; technology is not mature enough for application on a large scale for bulk chemicals advantage: simultaneous separation and concentration of lactic acid drawbacks: higher power consumption; small amount of byproduct salt; need for substantially more information for commercial use advantage: reliable technology drawbacks: regeneration of ion-exchange resin and adjustment of feed pH to increase the sorption efficiency requires a large amount of chemicals; waste stream generated creates treatment/disposal problem advantage: well-established/reliable technology drawbacks: formation of high-boiling internal esters, dimers, and polymers of lactic acid during distillation advantage: large interfacial area for mass transfer can be obtained in a compact unit drawback: tendency to form emulsion advantage: large interfacial area for mass transfers in a compact unit drawback: complexity of operation and swelling/instability of the LEM advantage: large interfacial area for mass transfers in a compact unit drawback: often suffers from membrane instability advantage: continuous separation of products enhances the process productivity; avoids toxicity due to extractant by immobilization of biocatalyst in membrane drawback: difficult cleaning and sterilization 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 strains give higher productivity at higher pH; toxicity of extractant toward the microbial strain needs to be eliminated; development of new strains, which are robust and work at low pH, is required

coefficient and complexation constant, toxicity, and feasibility for backextraction. From the available study, it can be seen that Alamine 336 in proper diluent (octanol and oleyl alcohol) is the best extractant in terms of the distribution coefficient, toxicity, and feasibility for backextraction. For the diluent selection, oleyl alcohol is a better diluent than octanol. The solvent toxicity versus the microorganism can be prevented by immobilization of cells with 15% sunflower oil.25 For the forward extraction process suggested by Yabannavar and Wang,21 Wasewar et al.’s work53 can be used because, by removal of the product during fermentation, the pH and the product concentration were maintained constant. For backextraction, the gasantisolvent-induced method is the most suitable method because this process does not require any toxic material like TMA and also the energy requirement is low because of the lack of a distillation step compared to other processes. The process suggested is a sustainable process because it does not consume any extra reagent and also does not produce a large waste stream as in the conventional process. 15. Scope and Directions for Future Work As discussed earlier most extractants have a very good extraction capacity at lower pH of the media. On the other hand, most microbial strains available for conversion of glucose to lactic acid afford high activity at higher pH. This is the classical dilemma faced by the process developers. In view of this, there is an urgent need to either develop extractants, which work at higher pH or strains and which yield good conversion to lactic acid at lower pH. In view of the rapid advances being made in developing tailor-made strains, the latter option

is likely to be more appropriate. Thus, future work should focus on the development of new strains suitable for operation at lower pH. The growing demand of lactic acid draws attention to the improvement of a conventional recovery process for lactic acid production. Reactive extraction using amine is an emerging prospective method for the recovery of lactic acid from fermentation broth. Economical evaluation data of various processes of lactic acid production and its recovery are not available. Therefore, it is necessary to focus on the economical evaluation of various processes of lactic acid production and 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 coefficient kmn ) rate constant for a reaction that is mth order in species A and nth order in species B [kmol m-3 s-1 (m3 kmol-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)

Ind. Eng. Chem. Res., Vol. 43, No. 19, 2004 5981 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 phase org ) organic phase T ) total 0 ) initial Superscript * ) equilibrium

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Received for review January 9, 2004 Revised manuscript received May 17, 2004 Accepted June 21, 2004 IE049963N