Document Type : Review Article


Chemical Engineering Department, Faculty of Engineering, Ahmadu Bello University, Zaria, Nigeria


This article reviews the potential application of deep eutectic solvents (DESs) for lactic acid production from lignocellulosic materials where DESs could be used as both preatreatment and extraction solvents as an alternative to the conventional organic solvents and ionic liquids. From literature survey, conventional methods currently explored for lactic acid (LA) production have several drawbacks of low yield, impure LA, low distribution coefficient, high cost of solvents, and non-recyclability of the solvents. Deep eutectic solvents (DESs) is paramount in LA production as  could enhance biotechnological development in obtaining higher yield of LA through better recovery as compared with the conventional extraction methods. The prospects of using DESs for LA production is huge in that, their unfavorable properties can be overcome by tailoring them through changing the nature of the molar ratio of hydrogen bond acceptor (HBA) to hydrogen bond donors (HBD), by adding appropriate amount of water if the DESs is highly viscous, by changing temperature or pressure and formation of ternary deep eutectic solvent through combinations of more components. DESs differs from the conventional organic solvent and ionic liquids as it offers several advantages  of recyclability, biodegradability, less volatile, non-toxic, non-flammability, high tuneability, high dissolution capability, ease, short time of preparation, and low costs as both pre-treatment and extraction solvents, but its feasibility for LA production has not been tested yet.

Graphical Abstract

Prospect of Deep Eutectic Solvents in Lactic Acid Production Process: A Review


Main Subjects

  1. Introduction

The increasing demand of lactic acid (LA) is due to its wide applications in production of polylactic acid, cosmetics, pharmaceutical, food and beverages as well as the increasing adoption for eco-friendly packaging materials. Numerous challenges and limitations have been identified during production and purification of lactic acid from fermentation broth using the conventional methods. Thus, to increase yield and purity of lactic acid, green solvents as substitutes for volatile organic solvents (VOCs) and ionic liquids (ILs) should be sought for and the need for shift towards green solvent should be the central focus of researchers supplemented with the novel efficient pre-treatment methods as well as solvents with minimal or without generation of hazardous by-products and innovative lactic acid bacteria (LAB) strains have to be developed to assure efficient lactic acid  production [1].

Lactic acid is a water soluble organic compound produced via breakdown of carbohydrates [2]. It has a general molecular formula of CH3CH (OH) COOH, white in solid state, colorless in liquid state and miscible with water [3]. Lactic acid is chemically known as 2-hydroxypropanoic acid, additionally called milk acid and the majorly occurring carboxylic acid in nature that found applications in many industries [1]. Lactic acids is one of the most essential platform chemical for production of diverse  products in food, pharmaceutical, textile, chemical, and cosmetics industries, and also used for production of poly lactic acids which is also a platform material in polymer industry [4]. According to Battula et al. [5], lactic acid is a basic chemical used as feedstocks for producing different products via fermentation process. It was reported initially that lactic acid was observed to be found in milky by Scheele when he initially discovered it in 1780. By 1789, it was named as Acide lactique by Lavoisier, while Charles. E Avery was the first to commercially produce lactic acid in 1981 in Littleton, Massachusetts, the USA [1]. It is an organic acid containing a dual functional group: hydroxyl and a carboxylic acid, as displayed in Figure 1.

Due to its versatile applications in biotechnology, the demand of lactic acid is on the increase globally. However, the increasing adoption for eco-friendly packaging and the expanding scope of lactic acid utilization in end-user industries are two reasons that will provide a large market opportunity. However, raw material processing price fluctuation is a key stumbling block to market expansion [6]. 

Figure 1. Structure of Lactic acid

  1. Lactic Acid Market

According to USA based research website,, from 2015 to 2022, the market is expected to increase at a compound annual growth rate (CAGR) of 16.9%, from USD 1,275.00 million in 2014 to USD 4,129.19 million in 2022. The worldwide lactic acid market was 750.00 kilotons in 2014 and is expected to reach 1,844.56 kilo tons by 2022, increasing at a CAGR of 12.9 percent from 2015 to 2022. They also reported that food and beverage applications had the biggest piece of the market pie in 2014, preceded by industrial applications. In 2014, the food and beverage category accounted for more than 40 percent of the total pie. Industrial applications, on the other hand, are expected to grow the fastest. From 2015 to 2022, it was expected to expand at a CAGR of 18.3%. By 2028, the worldwide lactic acid market is estimated to be worth USD 5.02 billion, while from 2021 to 2028, it is anticipated to grow at an annual rate of 8.0 percent [GVR, 2020]. The rising demand for lactic acid in different end-use sectors, such as industrial, food and beverages, and pharmaceuticals, may be linked to the market's expansion, particularly in emerging nations such as India, China, and Indonesia [GVR, 2020]. Furthermore, demand for this product as a feedstock in the manufacturing of polylactic acid (PLA) is expected to boost the global market. PLA became the most popularly applied material of industrial importance in terms of volume and income in 2020, mainly to its increasing use in the production of biodegradable and biocompatible goods [1].

GVR, [7] reported that polylactic acid is becoming a major applications accounting for about 30% of LA as of 2018 as a results of its wide applications in packaging, agriculture, 3D printing, textiles and filaments with packaging expected to continue to be the largest application because of its thermal and mechanical properties display by PLA, and thus makes it suitable material for packaging. The quest for renewable material has become the focus of researchers in an effort to shift a fossil-based society towards a sustainable and carbon-neutral society [8]. Hence, lactic acid (LA), a biodegradable raw materials derived from renewable resources, represent a promising substitute to replace the standard petroleum-based polymeric materials as it is used for production of polyester, a major material for production of polymeric materials [9]. Food industry is the second largest user of LA with 26% followed by pharmaceutical industry of 20% while cosmetics and chemical industries accounts for about 14 % and 10% of the total LA produced annually. Table 1 presents the summary of application of lactic acids in various industries.

Table 1. Summary of application of lactic acids in various industries

Lactic acid has a huge industrial applications, and as a result, demand is expected to grow in the future. From history, lactic acid is manufactured from materials such as diary waste (whey, skim milk, and paneer whey), starch, glucose, molasses, and lactose [10]. These substrates provide the benefit of generating pure LA without the requirement for pretreatment, as well as lower recovery costs [11]. However, the uses of traditional feedstocks contend emulously with the supply of foods and feeds hence making production cost very high. Therefore, producing lactic acid via cheap carbon sources and huge agricultural waste has now become alternative sources for lactic acid production [12]. Feedstocks like refined sugar such as glucose or sucrose sources used in the production of lactic acid required high amount of expensive nitrogen (yeast) so as to produce LA which is not economically suitable [12]. Thus, the need to consider lignocellulosic materials as a substitute for refined sugar.  According to Coelho et al. [13], raw materials account for about 68% of total cost of lactic acid production. As a result, research is being directed towards using inexpensive, renewable, and sustainable lignocellulose biomass as a competitive and ecologically acceptable alternative [1]. Lignocellulosics materials are one of the major abundant renewable resources currently. It consists of cellulose, hemicellulose, and lignin. Cellulose is homopolymer of glucose in the form of crystal and it is resistant to depolymerisation, while hemicellulose is amorphous and heteropolymer containing C5 and C6 sugar with Xylan being the main component [10]. Depolymerization of glucose polymers to produce fermentable sugars is necessary for microbial fermentation. Hence, pretreatment of lignocellulosic materials is paramount [14]. Lignocellulosics has advantages of not competing with food crops such as corn, rice, cassava, and sorghum. It is the widely spread, abundant, inexpensive, and renewable feedstock for large scale production and contain high glucose content compared to starchy crop [11]. Thus, some agricultural wastes such as sugarcane bagasse, corn cob, banana peel, rice husk, microalgae, etc. need to be examined as feedstocks for lactic acid production. A huge variety of microorganisms including bacteria, fungi, microalgae, yeast, or cyanobacteria may be used to manufacture LA by means of fermentation [15]. However, research on the usage of lactic acid bacteria (LAB) accounts for approximately 90% of the literature on the LA production. This is because of their potential to produce LA at very high yields and productivity [16]. Lactic acid microorganism (LAB) is various series of microorganisms that make contributions to a huge variety of fermentation activities [1]. They stated that because of the well-documented health-promoting characteristics of some LAB, probiotic cultures including chosen strains in conjunction with bifidobacteria have been developed for use in the food sector. Gram-positive, non-sporing, non-respiring cocci or rods that generate lactic acid as the primary end product during the carbohydrates fermentation are the bacteria that make up this category. LA is produced from petroleum-derived compounds or from natural substrates fermented by microbes [17]. The chemical method uses acetaldehyde and hydrogen cyanide in the presence of a base to generate lactonitrile, which is subsequently hydrolyzed to yield D/L-LA combinations. Because the pure isomers have specialized industrial uses, the racemic mixture has less industrial value than the pure isomers [1]. Because it can be digested by the human body, the L (+)-LA is highly sought after in the medical, food, pharmaceutical, and cosmetic sectors. Increased levels of D (–)-LA, on the other hand, may be detrimental to the human body [18]. The conventional purification of lactic acids by precipitation as calcium lactate produces huge quantity of gypsum (CaSO4), which results in low yield and productivity of LA, and also generates environmental problem since the large amount of (CaSO4) is greater than LA produces, and thus hindered the economic and commercial production of lactic acid through this process [19]. However, from literature, the better option and alternatives for purification of lactic acid is solvent extraction, but solvent extraction efficiency is limited by high toxicity of conventional organic extraction agent, and thus developing an efficient separation and purification techniques that lower the cost of production of LA from the fermentation broth is a major challenge hindering lactic acid productivity and yield [20]. Conventional organic solvents usually have the problem of high toxicity, volatility, cost, and non-biodegradability [2]. ILs have gained a lot of attention because of their non-volatility and negligible vapour pressures; however, they have limitations of high cost, complex synthetic, purification procedures, low moisture tolerance, toxicity, and biodegradability [21]. Till-date, various methods have been tested for the LA production from the fermentation broth to reduce production costs, amount of effluents, and thus decreasing the negative impact towards the environment [22]. Precipitation, adsorption, solvent extraction, reactive distillation, and membrane separation process are some technologies used as an alternative for the conventional process [3]. Despite these approaches been utilized, there is need to improved lactic acid yield through environmentally friendly and low-cost means through the DESs uses. Although, from literatures, the DES uses as extractant and pre-treatment of lignocellulosics feedstock for lactic acid production have not been widely and efficiently investigated. The aim and objectives of the paper to review the various methods that have been used for production of lactic acid and highlight the promising biotechnological solutions that deep eutectic solvent offers in solving the persisting problems of inefficient LA production and how DES can  significantly reduce production costs of LA from local materials. Also, this review is aimed at inspiring researchers towards the uses of novel solvent in lactic acid production and to persuade government and non-governmental organizations to provide financial assistance.

  1. Deep Eutectic Solvents (DESs)

Interest in developing and advancing more efficient solvents has been the focus of researcher lately due to need for greener solvents of green chemistry. DES is a liquid that is usually made up of two or more compounds that can self-associate, often by hydrogen bond interactions, to form a eutectic mixture with a melting point lower than the melting point of each individual component [23]. Deep Eutectic Solvents (DESs) constitute an organic salt with negligible vapor pressure and is non–flammable which are suggested substitutes for volatile conventional organic solvents [24]. DESs has several applications as it can be used for CO2 capturing, metal processing, extraction/separation, solvent electrocatalysis, development/reaction medium, electropolishing, electrochemistry, hydrometallurgy, and as catalyst, or catalyst carrier, etc. [21]. Figure 2 depicts the total publication of DESs from 2004 to 2020 indicating the rapid acceptability and versatility of this green and novel solvent.

Figure 2. Total publications for DESs by 2021 [25]

The DES uses for biotransformation are gaining a lot of interest owing to its action on enzymes like cellulose, lipase, and protease, etc. Thus, there is a need to evaluate biological interactions of DESs and their utilization in biotransformation. DES is similar to ionic liquids; however, ionic liquids (ILs) were introduced as substitutes for the conventional organic solvents [24]. This is as a result of their low vapor pressure [26]. Thus, a new and recent group of solvents similar to ionic liquids were introduced by [23] in 2004 and referred to it as “deep eutectic solvents” (DESs). DES is a combination of hydrogen bond donor and hydrogen bond acceptor at a temperature lower than the temperature of individual components. Furthermore, deep eutectic solvent has some essential characteristics such as non-flammability, low toxicity, high tuneability, low vapor pressure, high biodegradability, and good biocompatibility [24-27]. These important features of DES increase their potential utilization in various biochemical applications when compared to ionic liquids or conventional organic solvents [28]. Traditionally, although biotransformations have been performed in conventionally organic solvents such as methanol, hexane, and acetone, they normally cause enzymes denaturation [24]. Where DES dissolves the substrates without enzyme activation [24]. The aim of this review is to highlight the DES importance as a substitute in the production of lactic acid from agricultural feedstock. Lately, from literature DES have displayed good results in different biotransformation reactions. For example, DES have been successfully established as solvent for various chemical reactions such as metal electro-deposition [29] and enzyme-catalyzed reactions [30-32] and in liquid separation and nanoparticle functionalization [33]. DESs have been further applied as green solvent for extraction in biological materials including DNA and RNA [34-35]. From literature to the best our knowledge, DES has not been used to produce lactic acid. DESs are classified into the following four different types based on the components mixed. Table 2 provides various types of DESs and their typical HBAs and HBDs DESs samples can be synthesize in different molar ratios of hydrogen bond acceptor (HBA) i.e. Choline Chloride (ChCl) and hydrogen bond donor (HBD) such as urea, glucose, sorbitol, oxalic acid, glycerol, ethylene glycol, etc. in an incubator shaker at an appropriate molar ratio.

Table 2. Various types of deep eutectic solvents and their typical combinations

3.1. Preparation of deep eutectic solvents

There are two methods of preparing deep eutectic solvents (DESs); a vacuum evaporation and a heating technique. Vacuum Evaporation technique: Various components at appropriate molar ratios are dissolved in water and evaporated at 50 C with a rotary evaporator. The liquid solution is then covered with silica gel into a desiccator until they reach a regular weight. Heating technique: this technique is used to prepare DESs with a known quantity of water. The two-component mixture with calculated quantities of water is positioned in a beaker with a stirring bar and cap and heated in a waterbath at a temperature range of 50 C to 80 C with continuous agitation until a clean homogeneous liquid is formed, normally approximately 30-90 min) [36]. Figure 3 demonstrates a typical combination of two component form a deep eutectic solvent.

Figure 3. A schematic illustration of two component form a deep eutectic solvent (Choline chloride-urea) [29]

Physicochemical and thermal properties of DESs will can enhanced pretreatment and extraction  includes; pH, solvatochromic parameters, refractive index (RI), density ,surface tension, freezing temperature (Tf), viscosity, decomposition temperature (Td), octanol-water partition coefficient (Kow), flammability, and miscibility [21]. These properties depend on the composition and types of DESs used. Key advantages of DESs over the conventional volatile organic solvent used in lactic acid production includes recyclability [21], biodegradability, less volatile, and non-toxic [37].

The preparation of DESs is simple; no solvent or product purification step is required because no by-products are formed [38]. They are analogues to ionic liquids (ILs) but an enhanced ILs. DES is formed by cation, anion, and complex agents, while ionic liquids are formed by cation and anion only. Deep eutectic solvent has some essential characteristics such as non-flammability, high tunability, low vapor pressure, high biodegradability, low toxicity, and good biocompatibility [24-27]. They have high dissolution capability, i.e. their ability to donate and accept protons and electrons, which facilitates the formation of hydrogen bonds between molecules.

Payam and Ghandi [39] also reported that DESs is attracting more attention as green solvents, owing to their characteristics like ease and short time of preparation, low toxicity, good biodegradability, and low costs. DESs can also be used for extraction of essential chemicals from biomass, and thus can be used to overcome the challenges of separation and purification of sugar based chemicals from lignocellulosics materials since its guarantee only the dissolving of sugar molecules in biomass rather than further conversion into the undesirable products [36]. DESs have been used for pretreatment of biomass, especially carbohydrates since various conventional solvent like H2SO4, trifluoroacetic acid, KOH, and ionic liquids have been utilized and they are toxic, high cost, not environmentally friendly. Also, higher value of hydrogen bonding enhanced easy break of lignin in the cellulose [24]. Utilization of DESs for treatment and conversion of lignocellulosics materials are attracting more attention. Ren et al. [40] produced a DES; allyltriethylammonium chloride: oxalic acid at ratio of 1:1 for pre-treatment of cellulose and they were an enhanced solubility of 64.8%. Sirviö et al. [41] utilized Choline chloride: Urea (molar ratio of 1:2) DESs for pretreatment of cellulose into individual nano-filbrils and reported that it is a new way of achieving nanofibrils cellulose without cellulose without chemical or mechanical modification of cellulose. They observed that Choline chloride: Urea pre-treatment remarkably improved nano-fibrillation of the pulps compared to when using NaOH as solvent. The uses of DESs for lactic acid production have not been tested. They also stated that DESs can serve as solvent and catalyst for the production of bioactive compounds. In their work, they applied three DESs namely; ChCl: urea CCU, ChCl: oxalic acid CCO, and ChCl: glycerol CCG to examine the isomeric distribution of xylose, fructose, N-acetyl-D- glucosamine and glucose in D2O. Hence, there is potential, that DESs can be utilized with glucose to produce derivatives such as lactic acid. Wang et al. [42] reported that DESs has a good interaction with enzymes and microorganism hence a good solvent for pre-treatment, extraction, separation, and purification processes to produce valuable products from plant biomass. The intra-molecular hydrogen bonds in them which aid in breaking hydrogen bond in lignocellulosics materials and thus make these materials soluble and high conversion into useful products [36]. Table 3 lists several studies on different applications of deep eutectic solvents.

Table 3. Several studies on different applications of DESs

Among several studies carried out with regards to the use of deep eutectic solvents (with details presented in Table 3). Some of the application of DESs considered entails pretreatment of biomass [21-54], delignification of lignocellulosics materials extraction [43-59], synthesis and physicochemical characterization of DESs 46-68, biodiesel production [46], synthesis of bio compounds such as protein [64], and cellulose dissolution [40-69]. From literature and to the best our knowledge, deep eutectic solvent has not been used for production of lactic acid. Hence, there is need to carry out feasibility studies and an investigation into the production of  platform bio compounds like lactic acid owing the potentials of  its physicochemical characteristics such as biodegradability, less toxicity, non-volatile, cheap, recyclable, and  highly tuneable unlike the conventional solvents that have been utilized in the production of lactic acid. Likewise, DESs ability for cellulose dissolution boost further prospects of its used in production of bio compound such as lactic acid. Further survey of literature has unveiled several works that did not pay attention to the optimization and kinetics studies of DESs application for delignification, extraction, etc. which are necessary for establishment, commercialization, and scale up of pilot plant of such production process like lactic acid from lignocellulosics materials. No literature has considered the feasibility of pilot study of DESs for extraction and pretreatment. Furthermore, there is no literature currently establishing the techno-economic analysis of the uses of DESs as a substitute for conventional and ionic liquid used for several applications. Despite the existing application of DESs for biomass treatment and conversion into valuable products, there are many contingencies for designing more efficient DESs as a result of complexity of biomass. Moreover, the major challenges in producing most bioactive compounds are in the purification stages. Hence, the need to develop a solvent that can give high purity and better extraction efficiency of these valuable compound such as lactic acid.

  1. Lactic Acid Bacteria (LAB)

Microorganisms that are capable of producing LA are: Bacteria fungi and yeast. Lactic acid bacteria refer to collection of gram-positive, non-spore, and rod-shape bacteria belonging to the genera set of Atopobium, Lactobacillus (LB), Aerococcus, etc. [71]. One of the key reasons for the use of bacteria for lactic acid production in industry is because they do not have negative health effects compared to fungi and yeast [72]. Examples of lactic acid bacteria (LAB) are Bacillus strain, Escherichia coli, L-casei, L-delbruki, etc. [72]. LAB can produce LA anaerobically via glycolysis with high yield and productivity. The main disadvantages of using fungi for LA production is that more by-products (tamaric acid and ethanol are produced than the desired LA [11]. Based on the end product, LAB can be group into the followings:

4.1. Homofermentative LAB

This produces lactic acid as the major output from sugars e.g., Bacillus coagulan, L-casei, L- delbruki, and L-bulgaricus.

4.2. Heterofermentative LAB

This produces less yield of LA due to production of by-product such as ethanol, acetic acid, and CO2 e.g. L-acidophilus. Advantages of Bacillus coagulans over other LABs includes low nutrients demand, it can withstand low to moderate temperature fermentations, give high optical purity of LA, ability to utilize both hexose and pentose, undergoes homo-lactic fermentation and exhibit less glucose repression compared with other LAB [10].

  1. Lactic Acid Production

There are basically two methods of producing LA. These are fermentation and chemical methods as depicted in Figure 4.

5.1. Chemical method of lactic acid production

Here, acetaldehyde is the starting material for the chemical route. Figure 4 demonstrates the LA synthesis via chemical method. Providing a racemic mixture of LA, where hydrogen cyanide is added along with a base to produce lactonitrile at an elevated atmospheric pressures, accompanied by distillation to recover the lactonitrile crude, and hydrolysis with concentrated sulphuric acid, to give lactic acid and ammonium salt [73]. Furthermore, to achieve a higher purity, the lactic acid reacts with methanol to produce methyl lactate, passing through a distillation step to be further hydrolyzed by water, obtaining lactic acid and methanol [8].

5.2. Fermentation method of lactic acid production

This method of production of LA involves the uses of bacteria via fermentation process using carbohydrate sources containing C5 and C6 sugars [74]. It is the most frequently used method or industrial production of LA because of high yield and purity. Lactic acid produced via fermentation has several merits over the chemical synthesis route as the former has low energy consumption due to low temperatures employed, it is more cost effective and availability of a wide range of low-cost substrates [13-76]. According to Ajala et al. [1] close to about 90% of LA production globally is via fermentation methods. Lactic acid fermentation hinges on factors like the lactic acid bacteria used, feedstock, and nutrients present in the media [5]. There are mainly three methods of fermentation process which includes continuous, batch and fed-batch fermentations. Figure 4 show the various step in production of lactic acid via fermentation and chemical methods.

Figure 4. Process steps for production of lactic acid via different methods

The following steps show the mechanism of LA production via the conventional method:

Fermentation: Under anaerobic condition, glucose is broken down into LA.

5.3. Downstream process of lactic acid (Purification)

Presently, calcium lactate, is the most widely used purification method for lactic acid production; a process involving calcium hydroxide precipitation and it has been applied by the world largest producer of lactic acid; Nature Works and Purac in lactic acid production from starch [77]. However, this method is limited by high consumption of sulphuric acid, generation of gypsum, and low productivity of LA. It has been a challenge to design an efficient and cost-effective downstream process for lactic acid purification. Not only due to the strong affinity of LA towards water, its low volatility, and its probable decomposition when it is exposed to the elevated temperatures, but also due to the presence of various organics acids in the fermentation broth that present similar properties to LA [78]. Making conventional separation approaches such as distillation or solvent extraction with standard organic solvents unprofitable [8]. Table 4 lists various methods of recovery lactic acid from fermentation broth and the need to use new techniques of deep eutectic solvent as an alternative to conventional methods.

Table 4. Various methods of recovery lactic acid

Membrane filtration is another conventional method of lactic acid production that involves; electrodialysis and nanofiltration present promising results, including low effluent generation, low chemical consumption, and low energy conditions [9]. It can be implemented in situ to remove the lactic acid via fermentation broth continuously, maintaining the operational pH. A double electrodialysis process has been further developed successfully to produce concentrated lactic acid using an initial electrodialysis unit to remove the multivalent ions succeeded by a water-splitting unit with bipolar membranes achieving a high recovery yield. However, Komesu et al. [3] highlighted polarization and fouling problems which limits the application of electrodialysis on a large scale. They also reported that additional process steps should be implemented to achieve lactic acid with high purity for polymerization applications. These additional process steps could make the whole process of using electrodialysis not economically viable hence the need to look for alternative techniques that will give high purity of LA using suitable solvent such as DES. Solvent extraction efficiency is limited by high cost and toxicity of conventional organic extraction solvents such as acid and base. Hence, the need to use green solvent (DESs). Joglekar et al. [79] stated that in terms of obtaining high purity of lactic acid, reactive distillation becomes an attractive alternative, where the lactic acid reacts with alcohol, followed by a distillation of the ester and hydrolysis to obtain the free lactic acid and alcohol. They noted that esterification is the best option for downstream processes that allows the separation of lactic acid from other organic acids, due to the differences in boiling points of their ester compounds [78]. Generally, this reactive distillation presents thermodynamics limitations, therefore, excess amount of alcohol and rapid removal of water are common practices to obtain high yields (between 60% to 100% - depending on the implemented water removal method). However, the presence of impurities in the feed stream such as residual sugars and proteins affect the performance of the catalyst, cation exchange resins, complicating steady state operation [78].

According to Urrea [8], some downstream processes that can be used to separate and purify lactic acid via the fermentation broth in industrial processes has been elucidated and that some improvements to the conventional method have been found over the years, but still, there is need to further investigate others means of production of lactic acid and the need to develop a more efficient and economically attractive process to potentialize the production of lactic acid. Based on the report of Joglekar et al. [79], several techniques for separation and purification have been suggested in literature. However, the common method involves lactic acid precipitation using calcium hydroxide, while the recovery process is carried out using excess sulphuric acid which generate huge amount of Calcium sulphate as waste [82]. As a result of chemical use of (H2SO4) and CaSO4, the LA purity decreases and making the whole process not environmentally friendly. However, researcher are currently focusing on alternative techniques for recovery and purification of LA from fermentation broth [2].

5.4. Feedstock for lactic acid production-lignocellulosic materials

According to Ameh et al. [82] any organic materials available in a renewable form such as food residues, forestry feedstocks, aquatic plants, marine algae, agricultural residues as well as energy crop can be term as lignocellulosics biomass. López-Gómez et al. [12] reported that fossil raw materials are being depleted, and this is directing society towards using renewable natural resources to fulfill the growing demand for goods and energy. Moreover, renewable resources are more evenly distributed on earth than fossil resources. Thus, the uses of renewable resources could enhance the use of local resources. Pretreatment of lignocellulosics feedstock is necessary in order to reduce recalcitrance and to enhance the yield of fermentable sugar via enzymatic hydrolysis [83]. According to Krishnan et al. [84], pre-treatment of lignocellulosic materials reduces carbohydrate degradation and toxic products after fermentation of microorganisms. Various pre-treatment methods have been used by researchers to treat different lignocellulosic materials [85-86]. Such methods includes physical pretreatment like milling (size reduction) [87] and irradiation [88]; physical and chemical treatments, using water or steam explosion [89], ammonia pre-treatment [87], organic and ionic solvents [90], supercritical fluids, acids / bases, and sulfite pre-treatment [87], nitrobenzene and copper [91], and biological method of  pretreatments using bacteria and fungi [92]. Table 5 lists several studies on lactic acid production.

Table 5. Several studies on lactic acid production

Among the several studies carried out with regards to the use of feedstock materials for LA production (with details presented in Table 5). Some of the feedstock considered entails Cassava [96-110], sugarcane bagasse [113], Sweet sorghum juice [2], corn steep [93-102], corn flour [101], ground nut shell [95], whey [106], yam peel [1], and food waste [109] where the report for the use of corn cob was found to have shown the highest yield (82 %), while the cassava has shown the least yield with 8.30 %.

The use of sweet sorghum juice, cassava peels, sugarcane bagasse, rice husk, and corn cob,  for the production of lactic acid has been proven from the reported research works to be of a high yield confirming the materials to being a good potential resource that aid toward the commercialization of lactic acid in developing nations like Nigeria, where these resource materials are wide disposed randomly within its surroundings as waste for animals to feed on or allowed to just decompose and pollute the environment. It also provides food security as the feedstocks are not sources of food. Although the Nigerian state stands out among agricultural oriented Africa countries, with many lignocellulosics crops such as sugarcane, maize among others, largely growing and cultivated in Nigeria. It is however a serious worrisome decibel for most of these crops to be effectively utilized not only for lactic acid production, but also a consumable food stuff without necessarily hiking the prices and affordability of these crops. Hence the need to strike out a balance between its commercial and economic benefits [114]. From Table 5, kinetic study and detail optimization of lactic acid needs more attention while study on pilot scale plant and techno economic analysis of LA production are also scanty in literature hence these calls for consideration of alternatives methods that will produce LA efficiently and pose no threat to the environment.

Price of pretreatment of materials to a great extent is one of the main limitations towards the development and economic viability of LA production by fermentation [77]. Hence, there is an urgent need for alternative pretreatment methods using solvents that are cost effective and eco- friendly (DESs).

  1. Mechanism of DESs as an Extraction Solvent for LA

It has been established in literature that one of the most challenges of DESs application is the illustration of its mechanism for the desire applications. Several authors posited that DESs is more of an art than science in understanding its mechanism for its various applications and full knowledge of its mechanism is still lacking in literature. So far and to the best of our knowledge, there has not reported any reaction mechanism for particular application, Hence, in understanding the mechanism of DESs as an extraction solvent for LA, The mechanism depends on the HBD and HBA of the components of DESs, The functional groups of each components used in the formulation of DESs, the hydrogen bond interaction and electron transfer between the DESs functional group to target a particular functional group in the solute to be extracted. Some characterization techniques such as physical properties of DESs and chemical analysis such as FT-IR, SEM, XRD, TEM, DSC, etc. should  be carry out to unveil the interaction between DESs and the target compound, by doing this, it will aid in reviewing the mechanism of DES for extraction. Greatly, to understand the DESs mechanism, a computational approach is required to fully understanding the mechanism of DES application. LA is also a good HBD for formation of DESs; hence, the mechanism is to formulate hydrophobic DESs that will have high affinity for LA from the aqueous solution. Our work is ongoing in the laboratory and in our subsequent publications we attempt to unveil the mechanism behind this novel solvent for it is used in LA extraction. Several authors recently make an attempt to explain the mechanism of DES for extraction. According Abbot et al [23], lignin is the only aromatic biopolymer in lignocellulosic biomass and the Earth's most prevalent renewable aromatic molecule.  It is a polymer made of p-coumaryl, coniferyl, and sinapyl alcohols that is heterogeneous. The three monolignols units polymerize in the phenyl rings several times to create the phenyl propanoid units, which are represented by the letters phydroxyphenyl (H), guaiacyl (G), and syringyl (S), respectively. As a result, lignin has a variety of functional groups available.  DES is a synthetic solvent created by combining hydrogen bond acceptor (HBA) with hydrogen bond donor (HBD) [23]. They reported that depending on the nature of the initial components, DES's characteristics can be modified based on the application need. Different DES types have been used in the pretreatment of biomass and the DESs received the greatest research are HBA: polyol and HBA: carboxylic acid. While DES made of polyol shown excellent efficacy in improving the efficiency of enzymatic hydrolysis, whereas the acid-based DES proved successful in lignin extraction [23]. It was reported from the literature that acidic DESs were more capable of fractionating and delignifying materials than basic and neutral DESs. This promotes the investigation of organic acid as a potential replacement for mineral acid in the processing of biomass. Hence, from the earlier finding that revealed acidic DES as a promising lignin extraction solvent. However, the mechanism of DESs extraction depends on functional groups in HBD and HBA of DES, the molar ratio of DES constituents that would lead to better performance in addition to characterization studies on DES-extraction products such as FT-IR, XRD, H-NMR.SEM, TEM, DSC, etc. and the other feasibility studies to further confirm their performance.

The mechanism of DES for extraction hinges on hydrogen bonding and electron transfer. Alkyl groups boost the oxygen's electron density in the acid's OH group by giving electrons. This increases the strength of the hydrogen bond between hydrogen and oxygen, which results in the creation of a weaker acid with weaker acid ionization.

The DES ability to donate protons in solvent-solute interactions will therefore increase as the length of the aliphatic chain is reduced. The hydrogen-bond acidity solvatochromic parameter measures this ability. To make lignin extraction easier, a higher value is preferred for dissolving the lignin-carbohydrate complex in lignocellulosic biomass. In terms of extraction, the alkyl ammonium ion is a unique cation that successfully creates an aromatic ring complex interaction between the quaternary ammonium ion’s electron clouds and the aromatic rings delocalized Π-electron clouds of biomass. The alkyl ammonium ion's in the HBA which is somewhat positively charged H- atoms are naturally surrounded by a Π-electron cloud, which considerably aids in the quaternary ammonium ion's attachment to the aromatic molecule. Figure 5 depicts a typical mechanism of extraction using DESs.

Figure 5. Mechanism of extraction

The creation of a contact Π-aromatic interaction pair that may be more stable than the ion pair between tetra-alkyl quaternary ammonium ions and anionic residue of aqueous solution is facilitated by cation-aromatic interaction. The cation Π-non-covalent relationship between an inorganic cation and the cationic moiety of an organic molecule and the Π-electrons of hydrocarbons like alkenes, alkynes, or aromatics is referred to as a cation-interaction. This interaction is in line with Dougherty and Stauffer's theory, according to which the interaction between charge-quadrupole and charge polarizability is what causes the major binding forces in the complexing of Me4N+ (thymol) with lactic. Therefore, it might be said that the interaction between cations and aromatics reflects the extraction mechanism. DES have been used for extraction of fatty acids from food waste, lignin from biomass and metals from waste water hence, it has potential to extract lactic acid from biomass.

  1. Prospects and Future of Producing Lactic Acid from Deep Eutectic Solvent

A variety of multipurpose deep eutectic solvents can be prepared with characteristics superior to those reported for conventional organic solvents such as butanol, trioctylamine, methanol, hexane, and ionic liquids (ILs). The deep eutectic solvents are less toxic, more biodegradable, and quicker and easier to prepare, easily recyclable and do not require further purification steps. Furthermore, their unfavourable properties can be overcome by tailoring them, for instance, by changing the nature of the salt or the molar ratio of HBA to HBD, by adding appropriate amount of water if the DESs is highly viscous, by changing temperature or pressure and formation of ternary deep eutectic solvent through combinations of more components to meet a desire target or properties for a particular application like azeotropic extraction.

The existing routes for the production of LA from agricultural residue and food waste could be optimized, with the possibility of taking full advantage of the features and advantages of deep eutectic solvents over conventional organic solvents. The future prospects of the application of DESs for cellulose dissolution and pretreatment of biomass have been established in literature [39-69]. Hence, the feasibility of a LA production via sugar fermentation and purification and in this case, DESs has the potentials to be employ as multifunctional agents as it can be used as pretreatment and extraction solvents [8]. Therefore, there is need to carry out feasibility studies and an investigation into the production of  platform bio compounds like lactic acid owing the potentials of its physicochemical characteristics such as biodegradability, less toxicity, non-volatile, cheap, and recyclable and  highly tuneable unlike the conventional solvents that have been utilized in the production of lactic acid. Similarly, DESs ability for cellulose dissolution boosts further prospects of its use in production of lactic acid. Further survey of literature has unveiled several works that did not pay attention to optimization and kinetics studies of DESs application for delignification, extraction, etc. which are necessary for establishment, commercialization and scale up of pilot plant of such production process like Lactic acid from lignocellulosics matertials. No literature has considered the feasibility of a pilot study involving the use of DESs for extraction and pre-treatment. Moreover, there is no literature currently establishing the techno-economic analysis of the uses of DESs as a substitute for the conventional and ionic liquids that have been used for several applications.  Nigeria, is nationally recognized to be highly involved in agricultural production, is rich in feedstocks, especially as waste products both from industrial and domestic uses. Although not quantified reports have emphasized that a high volume of waste is generated globally daily.  Food and Fruit wastes have also been identified as a feedstock for lactic acid production [109]. The abundance of this feedstock in Nigeria is due to its enormous consumption daily [115]. Instead of covering the land with these solid wastes, it would instead benefit the country to convert the enormous agricultural residue into a useful resource by producing lactic acid and reducing land pollution. Another feedstock that is much available in Nigeria, is pineapple peel. This is because Nigeria is the seventh largest pineapple producer in the world and the leading producer in Africa [116]. Therefore, it would be advantageous to use the peels disposed of as waste to produce economically useful lactic acid. Interestingly, paper and paper products consist about 35% by weight of municipal solid waste in Nigeria [117]. In addition, a large collections of Irish potato peels, sugarcane bagasse, corn cob, plantain peels, rice husk, banana peel, sweet potato peels, rotten waste tomatoes, and yam peels can largely find in Kano, Zamfara/Plateau, Katsina, Cross River, Kaduna, Bauchi, and Yobe states in Nigeria, according to the report of the Nigeria national beaureu of statistics (NBS) [2017-2019] for agricultural items production and cost.

Despite the existing application of DESs for biomass treatment and conversion into valuable products, yet there are many contingencies for designing more efficient DESs as a result of complexity of biomass. Moreover, the major challenges in producing most bioactive compounds is in the purification stages; hence, the need to develop a solvent that can give high purity and better extraction efficiency of these valuable compounds such as lactic acid. Using food waste like fruit waste or real food waste or even lignocellulosic biomass from agricultural residues where a single or multi-component can be models for production of lactic acid can be explored. Food waste can serve as potential biomass resources from many sources including households, restaurants, agricultural residues and food processing industries. Therefore, there is a need to investigate the feasibility of transforming biomass, single-component wastes, or multi-food waste into lactic acid using deep eutectic solvents. This is because DESs display properties that will enhance efficient production of LA such as high distribution coefficient, non-toxic recycleability and biodegradability and to the best of our knowledge, DESs have not been explored for this purpose.

Finally, employing DESs as solvent for dissolution of lignocellulosics feedstocks and further as extraction solvent for LA production could be a major step towards building an efficient and sustainable LA purification process since DESs composed of components which are simple or naturally occurring can be tuned, design, innovative, and suitable for extraction of LA and several other applications such as protein synthesis, peptides, and so on.

  1. Conclusion

This paper reviews the potential application of deep eutectic solvents for lactic acid production where DESs could be use as both pretreatment and extraction solvents as an alternative to conventional organic solvent and ionic liquids due to low yield, impure LA, low distribution coefficient, high cost of solvents, and non recycleability of the solvents associated with the current conventional methods currently been explore in the LA production.

Several techniques for separation and purification have been suggested in literature, the processes are not efficient while some are not environmentally friendly. Also, the common method currently applied uses precipitation by application of calcium hydroxide where the recovery process is carried out using excess sulphuric acid which generates huge amounts of Calcium sulphate as waste to the environment. Lignocellulosics materials as feedstock for LA production look desirable alternatives because they do not contest with food crops, very cheap, renewable, and abundantly available. One of the ways to reduce the cost of lactic acid is to source for low cost, cheap, renewable, and also materials that have properties such as high yield, negligible formation of by-products, higher productivity, and low impurity. DESs offer numerous social (acceptability and sustainability), environmental and economic advantages hence, more research is required to explore the potentials of this unique and novel DESs especially for production of platform chemicals like lactic acid. Finally, to increase yield and purity of lactic acid, green solvents as substitutes for traditional organic solvents (VOCs) and ionic liquids should be sought for. Lastly, novel pretreatment methods without or with minimal generation of hazardous by-products and innovative LAB strains have to be developed to assure effective LA production. The DESs properties could offer several advantages such as better pretreatment solvents, may give higher extraction efficiency and easily recyclable compared with conventional organic solvents and ionic liquids. Hence, there is need to carry out feasibility study of this novel solvents for its use in lactic acid production via fermentation.

Conflict of interest

The authors declare no conflict of interest.


The authors acknowledge the support of Chemical Engineering Department for providing facility for the ongoing experimental work.


John Enemona Oguche

Alewo Opuada Ameh

Tajudeen Kolawale Bello

N.S. Maina

Citation: J.E. Oguche*, A.O. Ameh, T.K. Bello, N.S. Maina, Prospect of Deep Eutectic Solvents in Lactic Acid Production Process: A Review. J. Chem. Rev., 2023, 5(2), 96-128.

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