Polylactic acid/Research Development

=Literature review=

Process Review
http://naldc.nal.usda.gov/download/4048/PDF L (+) lactic acid fermentation and its product polymerization by Narayanan et al reviews the production of lactic acid and its use as a plastic monomer. The synthetic route of lactic acid is four steps that involve fixating an activator cyanide group to an acetylaldehyde to form lactonitrile, hydrolysis of lactonitrile with sulfuric acid to yield lactic acid and ammonium salt. For purification via reactive distillation lactic acid is esterified with methanol to methyl lactate and water, methyl lactate is distilled, and hydrolyzed to lactic acid with the addition of water. The production of lactic acid from biological sources is through the fermentation of high energy carbohydrates to lactic acid by Lactic Acid Bacteria. Lactic acid is neutralized and precipitated with calcium hydroxide. Calcium lactate is collected and hydrolyzed with water. For purification lactic acid is esterified with methanol to methyl lactate and removed via distillation, before hydrolysis with water. Has use as hardener for cellophane.

"The choice of an organism primarily depends on the carbohydrate to be fermented. Lactobacillus delbreuckii subspecies delbreuckii are able to ferment sucrose. Lactobacillus delbreuckii subspecies bulgaricus is able to use lactose. Lactobacillus helveticus  is able to use both lactose and galactose. Lactobacillus amylophylus and Lactobacillus amylovirus are able to ferment starch. Lactobacillus lactis  can ferment glucose, sucrose and galactose. Lactobacillus pentosus have been used to ferment sulfite waste liquor." Lactobacillus also have complex nutrition requirements. Rhizopus oryzae are also stereoselective LAB as well as yeasts such as Saccharomyces cerevisiae and Kluyveromyces lactis and have been investigated for their usefulness. Lactase enzymes are stereospecfic and heterolactic species have two isoforms, some species induce their second enzyme only under high concentrations of lactic acid. Genetic engineering on lactobacilli has shown success in controlling stereospecficity of products, reaction rate and yield; Rhizopus oryzae is also under study. Favorable feedstocks are high sugar or starch plants. Techniques to increase yield include pretreatments, simultaneous saccharification, and nutrient supplementation (especially nitrogen - yeast extract). Methods to remove lactic acid product from the fermentation batch include ion-exchange resins and electrodialysis.

Different bioreactor configurations have been studied and batch-wise and continuous reactor sketches are provide. Continuous cell recycle reactors have shown high performance and utilize membranes to retain cells while removing media. Cell immobilization by biofilm establishment shows higher performance to free floating culture systems. High cell concentrations make it much more difficult to maintain optimal conditions in all parts of the reactor and can stress the cells (stereoisomerization). "(a) lowering down of the pH of fermented broth (3.0 to 4.2); (b) Use of hydrophilic membrane and the volatile amine weak base (VAWB) to separate lactic acid from the fermented broth through the hydrophillic membrane to VAWB; (c) Regeneration of lactic acid from salts of weak amine base by selectively vaporizing the volatile amine base. This process can be repeated to ensure the efficient separation of free lactic acid and its salt. "

Polylactic acid technolgy by Henton (2005) reviews production, purification, and polymerization. There is information on Cargill Dow's plant capacities who dominate the market (economic significance), largest produces 400,000,000 lb and produces over half the market. Clostridium thermoaceticum is the highest yielding fermenter but requires pH control. Purification technologies utilize a variety of characteristics of lactic acid to separate it from the broth. Cell and macromolecule filtration followed by electrodialysis that is fed to distillation column, reactive distillation). Tin octoate is the basis catalyst for lactide polymerization which converts LA to stereospecific form. PLA characteristics include crystallinity which affects Tg and Tm.

Fermentation procedures
L(+)-lactic acid production by pellet-form Rhizopus oryzae R1021 in stirred tank fermenter by Bai et experimented with growth parameters effects on culture growth in a continuous run fermentor. Parameters under study included NH4NO3 concentration, CaCO3 addition timing, agitation speed and aeration rate, and inoculation concentration and effects on growth morphology and lactic acid were studied. Pellet form exhibits higher lactic acid productivities and inoculation of 10e6 spores/ml and addition of CaCO3 at 8 hours exhibited pelleted forms. Lactic acid yield was ~72.5% and with 300 rpm and aeration of 0.6 vvm yield increased to 74.5%. Biomass is limited by oxygen transfer, high biomass is necessary for high turnover of glucose to lactic acid. Biomass to lactic acid productivity was found to be highest with 2 g/l NH4NO3, 100 g/l glucose, 300-600 rpm, and 0.6-1.2 vvm. Repeated cycles using the R. oryzae culture showed sustained viability through the 7th cycle and an increase in lactic acid yield to 80%.

Lactic acid purification
Optimization of Batch Reactive Distillation Process: Production of Lactic Acid by Edreder (2010) develops a model for esterifying lactic acid with methanol and distills the methyl lactate, the lactic acid is recovered by hydrolysis. The purity analyzed was 80-99% molefraction, it took 4 refluxes to theretically reach the highest purity.

[http://144.206.159.178/FT/549/63720/1083859.pdf Process development and optimisation of lactic acid puriﬁcation using electrodialysis] by Madzingaidzo et al examines purification of lactic acid from fermentation broth using mono and bi-polar electrodialysis. A mono-polar membrane selectively allows cations or anions to traverse the layer, while a bi-polar layer is made of a cation and anion membrane that splits water molecules into H+ and OH- for charge balancing. An electrical current is applied to the dialysis chamber to separate molecules according to their charge and mono and bi-layer membranes create channels concentrated with certain components. In mono-layer electrodialysis a alternating semipermeable membranes starting with a cation membrane next to the anode (+), a dilute stream feeds through center from which lactic acid is concentrated through a anion exchange membrane towards the anode. Charge is balanced from an electrode rinse solution that circulates next to the electrodes. A bi-polar uses bi-polar membranes to separate the electrode rinse solution from the concentrating channels creating sections holding a base, salt and final acid form. A measurement of % current efficiency (current used to transport molecule from input to concentrated stream/ total current) is used to evaluate the process.

Lactic acid purification issued to Schopmeyer June 6 1944 covers a method to purify lactic acid from fermentation broth by the use of calcium carbonate salts and esterification with methanol for fractional distillation. The fractional distillation set-up includes a boiler containing methanol and lactic acid and a catalyst (H2SO4) that delivers vapors to a fractionation column that allows the separation of a concentrated lactic acid liquor of ~10-50%. The salting out of calcium lactate uses calcium sulfate which is concentrated and converted to acid form through treatment with sulfuric acid, calcium sulfate forms an insoluble fraction. The concentration was usually 40-60% lactic acid and ethanol can also be used as the esterification. The esterification procedure uses a steam jacket with the following substrate mole ratio 1.5:1:0.005 methyl alcohol: lactic acid: sulfuric acid. Start-up of purification uses 80% lactic acid substrate (depending on concentration), 20 methanol, and a small amount of catalyst. Steady-state is maintained by addition of substrates and catalyst, and recycling of methanol.

http://www.google.com/patents/US4771001

Polylactic acid polymerization
http://www.cem.msu.edu/~smithmr/Publications/ja9930519.pdf Stereoselective Polymerization for a racemic monomer with a racemic catalyst Direct Production of the polylactic acid stereocomplex from racemic lactide by Radano et al uses a stereoselective catalysts to polymerize L(+)- and rac-lactide to comprehensive products tacticity. Tacticity is the stero-relation between adjacent chiral subunit (same side or different side). Tacticity has important effects on the polymers interactions and crystallinity, and Poly L(+)lactic acid has a Tm = 180 and the poly rac-lactic acid Tm is near room temperature. Tsuji et al first noted the Tm of combined stereoregular L and D polymers was raised almost 50 C. The stereoselective catalyst was a Schiff base aluminum alkoxide.

Synthesis of polylactic acid by direct polycondensation under vacuum without catalysts, solvents and initiators by Achmad et al details a procedure. The authors recommend PLA be pursued using processing plants capable of fermenting feedstock, purifying lactic acid, and condensing the product as is proposed for the OSE product ecology. Streptococcus bovis is a LAB suggested for use but the species is also linked to pathogenicity. The process used by the researchers used three phases for treating the lactic acid and polymerizing its monomer: distillation, oligomerization, and polymerization. The reaction was carried out in 4 l sealable flasks, on magnetic stirrers and heaters, with temperature and pressure probes, and connected to a pressure regulator. During distillation sample temperature is brought to 150 C over 90 minutes and maintained for 60 minutes and PLA concentration increases from 90% to 100% as measured by acid-base titrations. Oligomerization phase was a reduction in pressure to 10 mmHg and temperature was raised to 200 C. The polymerization step was maintenance of the reduced pressure and temperature for 89 hours. The condensate was also separated with gel filtration chromatography and measured with a RI detector. Fourier Transform Infrared Spectroscopy was used to analyze molecules functional groups.

Melt/solid polycondensation of l-lactic acid: an alternative route to poly(l-lactic acid) with high molecular weight by Moon et al (2000) describes a method that yields high weight PLA on the order of 500,000 daltons through a condensation reaction using a tin chloride dihydrate/p-toluenesulfonic acid binary system. They report that reaction temperatures below the Tm (melting point) of PLA yields a better product and is referred to as melt/solid polycondensation. oligo(l-lactic acid) (OLLA) is mixed with tin(II) chloride dihydrate (SnCl2) (0.4 wt% relative to OLLA) and p-toluenesulfonic acid (TSA) (an equimolar ratio to SnCl2). The mixture is heated to 180 C and the pressure reduced to 10 torres over the period of an hour followed by maintenance for 5 hrs. The product consisting of 20,000 dalton polymers is ground and heated to 105 C under vacuum for 1-2 hr to crystallize the polymers. Solid-state post-polycondensation was initiated by increasing the temperature to 150 C and reducing the pressure to 0.5 Torr. Treatment was continued over 30 hours but molecular weight peaked between 2-10 hours and drastically reduced after 20 hours. The results showed a method to obtain high molecular weight PLLA with comparable characteristics to the lactide ROP synthesis. The method used here catalyzes the first step of dehydration to form lactide and the lactide ROP step follows. The high activity of the catalyst and the ability to move through the amorphous PLLA may be driving the reaction by concentrating ester tails and catalyst in the amorphous regions during crystallization.

Basic properties for film polylactic acid produced direct condensation polymerization of lactic acid by Ajioka characterizes the polylactic acid products of different catalysts and solvents under 130-250 C. Polymerization was commercially pursued from an isolated dilactide intermediate but direct polymerization is possible due to improvements in kinetic control, removal of resulting water, and suppression of depolymerization. Solvents controlled the rate of reaction based upon their boiling point and the ability to remove water and a Dean Stark trap used, diphenyl ether results shown. Tin and protonic acids catalysts were found to have superior performance with tin(II) chloride achieving highest efficiency and high molecular weights. Zinc catalysts produced maximum 150 kDa weight polymers at 160 C. Weights and flow rates comparable to dilactide process and usable for injection molding. D and L enantiomers were polymerized in ratios of 50/50 to 0/100 respectively. Pure L form had the highest strength and molecular weight. 13C NMR of direct condensation PLA showed 5 carbonyl signals, an additional lower signal from adjacent L subunits. Direct synthesis of PLA general protocol A reaction chamber with a Dean Stark trap 40.2 g 90% lactic acid and 0.14 g tin were dissolved in 400 ml organic solvent for 2 hr at 140 C. The trap was replaced with a tube containing 40 g molecular sieve (3 A) for azeotropic separation for 20 to 40 hr at 130 C. At half volume 300 ml chloroform was added and catalyst removed with filtration or extraction. PLA product was by precipitation by 900 ml methanol and washing over suction with methanol. Cyclic oligomer production 10.0 kg of 90% lactic acid azeotropically dried 81.1 kg diphenyl-ether organic solvent with 6.2 kg tin catalyst at 150 C for 2 hr. This was followed by recycling of solvent using 4.6 kg molecular sieve (3 A) for 40 hr at 140 C. The reaction was concentrated to 70 kg, cooled to 40 C, and PLA crystals collected. The reaction was concentrated to 5.8 kg. A 11.6 kg hexane was added to the filtrate and an oil separated with 5.8 kg acetonitrile and 1 M HCl. An oily substance was collected after 30 min of agitation and washed with 5.8 kg water. The washed product was dissolved in 2.9 kg chloroform and combined with 4 l isopropyl alcohol and a final precipitated product collected over suction and dried with reduced pressure. Final yield 350 g.

A Highly Active Zinc Catalyst for the Controlled Polymerization of Lactide by Williams et al (2003) details a Zinc alkoxide compound paired with a ligand that has high reactivity and high molecular weight products. Zinc is an attractive catalyst due to low cost but has complicating aggregation behavior. Ligands help prevent this behavior and modulate desirable characteristics; the ligand (HL) used for this study was made by refluxing N,N,N′-trimethylenediamine, paraformaldehyde, and 2,4-di-tert-butylphenol. The ligand was reacted with Et2Zn to yield LEtZn which was then reacted with EtOH to produce LZnOEt the zinc alkoxide catalysts. The catalysts structure was examined in solid state (X-ray crystallography, mass spectrometry) and catalytically relevant solution state (NMR, PGSE) and was found to be dimeric in solid state and monomeric in solution state. This information allows rate equations to be solved. The PLA MW was measured with SEC-MLS and monitored with 13C NMR. The catalyst was found to be effective in L/LZnOEt ratios up to and at concentrations as low as 0.7 mM, higher than any other zinc catalysts reported. The active site is the ethoxy group and reaction is sensitive to exchange agents.

Syntheis and Properties of High Molecular Weight Poly(Lactic Acid) and its resulting fibers by Zhang and Wang tests the polylactic acid polymerization melt/solid polycondensation process with a number of catalysts. The now commercial route uses a first step of azeotropic dehydration with reflux, in a high boiling point, aprotic solvent like diphenyl ether to produce 50 kDa polymers. The second step joins these fibers with reduced pressure and a tin and protic acid catalyst. This study uses SnCl2·2H2O/p-toulenesulfonic acid monohydrate (TSA) and SnCl2·2H2O/maleic anhydride catalyst for the first step and TSA in the second step. This improves upon Moon et al. with the addition of TSA in the second step because the environmental polarity was found to be shifted in the first step. Polymer MW had leveled off in step 1 but continued in step 2 with the addition of more catalyst (TSA). SnCl2·2H2O/maleic anhydride was found to be a more effective catalyst due to the less crystalline nature which allowed further polymerization in the amorphous regions. An increase in reaction temperature for the second step was found to be effective up to 180 C and degradative at higher temperatures. The process starts by combining 400 g distilled lactic acid is with the designated catalyst (0.5% wt SnCl2·2H2O and 0.4% wt TSA or maleic or succinic anhydride)and sealed in the reactor. The reaction is heated to 150 C 4 hrs, the reaction is then heated to 160 C and the pressure reduced to 500 Pa for 4 hrs. After an initial low-weight polymerization the reflux condenser is removed and 0.4% wt (of starting lactic acid) TSA is added to the reactor. The temperature is further increased to 180 C and the pressure reduced to 300 Pa for 10 hrs. The polymerization product was dried and processed used standard melt spinning procedures before a final draw between 150-200 C under nitrogen. The final fiber product was characterized with FTIR, DSC, an Ubbelohde viscosimeter, and tensile-testing machine. Final spinning produced a fiber made of high molecular weight polymers and has high tensile strength.

http://www.imm.ac.cn/journal/ccl/1208/120803-663-01061-p2.pdf

http://193.146.160.29/gtb/sod/usu/$UBUG/repositorio/10281082_Lonnberg.pdf

http://www.ch.ic.ac.uk/marshall/4I11/Coates2000.pdf

http://www.ch.ic.ac.uk/marshall/4I11/Coates2002.pdf

Polylactic acid value adding
| (Poly)lactic acid: plasticization and properties of biodegrable multiphase systems by Averous (2001) experimented with measuring the properties of PLA prepared with different plasticizers. Plasticizers included: glycerol, polyethylene glycol, citrate ester, PEG monolaurate, and oligomeric lactic acid. various mixtures of PLA with thermoactive starch polymers (TSP) were prepared and tested. Plasticizer treated samples show a decrease in Tg (glass transition temp) and therefore Tm (melting temp). Oligomeric lactic acid followed by low molecular weight polyethylene glycol were effective plasticizers while glycerol was ineffective. Finding effective methods to combine PLA and TSP would enhance the product.

http://www.e-polymers.org/journal/PAT2005ePolymers/page/Oral%20Presentations/Section%20B/Martino_Ver_nica_Patricia.pro.1728860278.pdf looks at the use of 4 plasticizers to increase beneficial characteristics for film.