Poly-lactic acids

Lactic acid is the smallest optically active organic molecule of natural origin with either l(-I-) or d(-) stereoisomers it is produced by animals, in plants, and 

Synthesis PL A is a thermoplastic aliphatic polyester which is formed by condensation polymerization of lactic acid, as mentioned in the preceding. Lactic acid is isolated from tapioca, corn and other plant root starches, sugarcanes, or other resources. Bacterial fermentation is normally used to produce lactic acid 

The polymerization of lactic acid to lactide or high-molecular-weight lactic acid-based polymers can be conducted in several ways  

1) Lactic acid through condensation polymerization to produce lower-molecular-weight PLA (degree of polymerization (DP) is normally less than 100). 

2) Lactic acid can be polymerized in solution to produce high-molecular-weight PLA. 

The thermal degradation of PGA proceeds through random chain scission at lower and through specific end-chain scission at higher temperatures. It shows better thermal stability than poly(lactic acid) and is, in a similar manner, sensitive to the presence of moisture. 

Direct polycondensation in the bulk through the reaction of hydroxy and carboxy functionalities of the lactic acid monomer with the elimination of water molecule has all the drawbacks associated with the character of an equilibrium step-growth polymerization. In addition, employing this polymerization method, the stereoregularity of the polymer cannot be controlled. This polymerization technique involves the use of a catalyst and reduced pressure.  

In the cationic ROP, only triflic acid and trifluoromethanesulfonic acid have shown potential as initiators for the polymerization of lactide. The polymerization starts by protonation or alkylation of carbonyl oxygen, which results in positively charged alkyl-oxygen bond and the propagation step involves cleavage of this bond. The PLA obtained by this route is optically active if the appropriate reaction temperature is chosen ( 50 °C) however, the product obtained at such temperatures is of low molecular weight. 

The ROP of lactide in the presence of metal compounds of tin, aluminum, zinc, titanium or zirconium as catalysts proceeds via the coordination-insertion mechanism. The initiators in this type of reaction are usually metal alkoxides. In the first step, temporary coordination of lactide through the carbonyl group with the metal in the initiator leads to increased nucleophilicity of the alkoxide and electrophilicity of the carbonyl group, thereby facilitating the insertion of the monomer into the metal O bond. This is the most investigated and applied method for the synthesis of PLA due to the mild reaction conditions, since the reaction proceeds via covalent species. High molecular weights of 200000 g mol are easily achievable with minimum side reactions and racemization. 

The most frequently used initiator for the polymerization of lactide is stan-nous(II)-ethylhexanoate (tin(II)-octoate), Sn(Oct)2. It is believed that the true 

PLA is a sustainable alternative to petrochemical-derived products, since LA can be produced on a mass scale by the microbial fermentation of agricultural products/by-products mainly the carbohydrate-rich substances (Nampoothiri et al., 2010). In 

Cosmetic industry / Lactic acid 1 H3C-C-COOH j OH / Chsmicai industry Chemical feedstock 

FIGURE 13.2 Chemical conversions of lactic acid to useful products. 

Department of Environmental and Life Sciences, Graduate School of Engineering, Toyohashi University of Technology, Japan 

Over the past several decades, polylactide - i.e. poly(lactic acid) (PLA) - and its copolymers have attracted significant attention in environmental, biomedical, and pharmaceutical applications as well as alternatives to petro-based polymers [1-18], Plant-derived carbohydrates such as glucose, which is derived from corn, are most frequently used as raw materials of PLA. Among their applications as alternatives to petro-based polymers, packaging applications are the primary ones. Poly(lactic acid)s can be synthesized either by direct polycondensation of lactic acid (lUPAC name 2-hydroxypropanoic acid) or by ring-opening polymerization (ROP) of lactide (LA) (lUPAC name 3,6-dimethyl-l,4-dioxane-2,5-dione). Lactic acid is optically active and has two enantiomeric forms, that is, L- and D- (S- and R-). Lactide is a cyclic dimer of lactic acid that has three possible stereoisomers (i) L-lactide (LLA), which is composed of two L-lactic acids, (ii) D-lactide (DLA), which is composed of two D-lactic acids, and (iii) meso-lactide (MLA), which is composed of an L-lactic acid and a D-lactic acid. Due to the two enantiomeric forms of lactic acids, their homopolymers are stereoisomeric and their crystallizability, physical properties, and processability depend on their tacticity, optical purity, and molecular weight the latter two are dominant factors. 

Poly(lactic acid) has three typical optical isomeric forms (i) optically active and crystalliz-able poly(L-lactide) (i.e. poly(L-lactic acid) (PLLA)), (ii) optically active and crystallizable poly(D-lactide) (i.e. poly(D-lactic acid) (PDLA)), and (iii) optically inactive and noncrystal-lizable poly(DL-lactide) [i.e. poly(DL-lactic acid) (PDLLA)]. Of these isomeric polymers, PLLA is most frequently used because its production cost is lower due to its joint mass production of 1.4 X 10 metric tons per year by NatureWorks LLC, which is owned by Cargil 

Bio-Based Plastics Materials and Applications, First Edition. Edited by Stephan Kabasci. 2014 John Wiley Sons, Ltd. Published 2014 by John Wiley Sons, Ltd. 

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Because lactic acid has both hydroxyl and carboxyl functional groups, it undergoes iatramolecular or self-esterificatioa and forms linear polyesters, lactoyUactic acid (4) and higher poly(lactic acid)s, or the cycUc dimer 3,6-dimethyl-/)-dioxane-2,5-dione [95-96-5] (dilactide) (5). Whereas the linear polyesters, lactoyUactic acid and poly(lactic acid)s, are produced under typical condensation conditions such as by removal of water ia the preseace of acidic catalysts, the formation of dilactide with high yield and selectivity requires the use of special catalysts which are primarily weakly basic. The use of tin and ziac oxides and organostaimates and -titanates has been reported (6,21,22). 

Polylactide is the generaUy accepted term for highly polymeric poly(lactic acid)s. Such polymers are usuaUy produced by polymerization of dilactide the polymerization of lactic acid as such does not produce high molecular weight polymers. The polymers produced from the enantiomeric lactides are highly crystalline, whereas those from the meso lactide are generaUy amorphous. UsuaUy dilactide from L-lactic acid is preferred as a polymerization feedstock because of the avaUabUity of L-lactic acid by fermentation and for the desirable properties of the polymers for various appUcations (1,25). 

Polymer Blends. The miscibility of poly(ethylene oxide) with a number of other polymers has been studied, eg, with poly (methyl methacrylate) (18—23), poly(vinyl acetate) (24—27), polyvinylpyrroHdinone (28), nylon (29), poly(vinyl alcohol) (30), phenoxy resins (31), cellulose (32), cellulose ethers (33), poly(vinyl chloride) (34), poly(lactic acid) (35), poly(hydroxybutyrate) (36), poly(acryhc acid) (37), polypropylene (38), and polyethylene (39). 

Other blends such as polyhydroxyalkanoates (PHA) with cellulose acetate (208), PHA with polycaprolactone (209), poly(lactic acid) with poly(ethylene glycol) (210), chitosan and cellulose (211), poly(lactic acid) with inorganic fillers (212), and PHA and aUphatic polyesters with inorganics (213) are receiving attention. The different blending compositions seem to be limited only by the number of polymers available and the compatibiUty of the components. The latter blends, with all natural or biodegradable components, appear to afford the best approach for future research as property balance and biodegradabihty is attempted. Starch and additives have been evaluated ia detail from the perspective of stmcture and compatibiUty with starch (214). 

In order to become useful dmg delivery devices, biodegradable polymers must be formable into desired shapes of appropriate size, have adequate dimensional stability and appropriate strength-loss characteristics, be completely biodegradable, and be sterilizahle (70). The polymers most often studied for biodegradable dmg delivery applications are carboxylic acid derivatives such as polyamides poly(a-hydroxy acids) such as poly(lactic acid) [26100-51-6] and poly(glycolic acid) [26124-68-5], cross-linked polyesters poly(orthoesters) poly anhydrides and poly(alkyl 2-cyanoacrylates). The relative stabiUty of hydrolytically labile linkages ia these polymers (70) is as follows ... 

FIGURE 9.32 Analysis of biodegradable poly(lactic acid). Columns PSS PFG 100 + 1000. Eluent TFE + 0.1 M NatFat. Temp 2S°C. Detection UV 230 nm, Rl. Calibration PSS PMMA ReadyCal kit. 

Most of the chiral membrane-assisted applications can be considered as a modality of liquid-liquid extraction, and will be discussed in the next section. However, it is worth mentioning here a device developed by Keurentjes et al., in which two miscible chiral liquids with opposing enantiomers of the chiral selector flow counter-currently through a column, separated by a nonmiscible liquid membrane [179]. In this case the selector molecules are located out of the liquid membrane and both enantiomers are needed. The system allows recovery of the two enantiomers of the racemic mixture to be separated. Thus, using dihexyltartrate and poly(lactic acid), the authors described the resolution of different drugs, such as norephedrine, salbu-tamol, terbutaline, ibuprofen or propranolol. 

Table 5-1. Enantioselectivities determined for several drugs. All experiments were performed at room temperature, except those marked with, which were performed at 4 °C. In some cases a lipophilic anion was used to facilitate the solubilization of the drug in the organic phases (PFj = hexafluorophosphate BPh = tetraphenyl borate). DHT = dihexyl tartrate DBT = dibenzoyl tartrate PLA = poly (lactic acid). ...

Lactic acid and levulinic acid are two key intermediates prepared from carbohydrates [7]. Lipinsky [7] compared the properties of the lactide copolymers [130] obtained from lactic acid with those of polystyrene and polyvinyl chloride (see Scheme 4 and Table 5) and showed that the lactide polymer can effectively replace the synthetics if the cost of production of lactic acid is made viable. Poly(lactic acid) and poly(l-lactide) have been shown to be good candidates for biodegradeable biomaterials. Tsuji [131] and Kaspercejk [132] have recently reported studies concerning their microstructure and morphology. 

RAFT polymerization has been used to prepare poly(ethylene oxide)-/ /wA-PS from commercially available hydroxy end-functional polyethylene oxide).4 5 449 Other block copolymers that have been prepared using similar strategies include poly(ethylene-co-butylene)-6/oci-poly(S-eo-MAH), jl poly(ethylene oxide)-block-poly(MMA),440 polyethylene oxide)-Moe -poly(N-vinyl formamide),651 poly(ethylene oxide)-Wot A-poly(NlPAM),651 polyfethylene ox de)-b ock-polyfl,1,2,2-tetrahydroperfluorodecyl acrylate),653 poly(lactic acid)-block-poly(MMA)440 and poly( actic acid)-6focA-poly(NIPAM),4 8-<>54... 

Polyester chemistry is the same as studied by Carothers long ago, but polyester synthesis is still a very active field. New polymers have been very recently or will be soon commercially introduced PTT for fiber applications poly(ethylene naph-thalate) (PEN) for packaging and fiber applications and poly(lactic acid) (PLA), a biopolymer synthesized from renewable resources (corn syrup) introduced by Dow-Cargill for large-scale applications in textile industry and solid-state molding resins. Polyesters with unusual hyperbranched architecture also recently appeared and are claimed to find applications as crosstinkers, surfactants, or processing additives. 

Special mention must be made of poly(lactic acid), a biodegradable/bio-resorbable polyester, obtained from renewable resources through fermentation of com starch sugar. This polymer can compete with conventional thermoplastics such as PET for conventional textile fibers or engineering plastics applications. Hie first Dow-Cargill PLA manufacturing facility is scheduled to produce up to 140,000 tons of Nature Works PLA per year beginning in 200245 at an estimated price close to that of other thermoplastic resins U.S. l/kg.46 Other plants are planned to be built in the near future.45... 

Poly(Lactic Acid) as a Biopolymer-Based Nano-Composite... 

Noda, L, Satkowski, M.M., Dowrey, A.E. and Marcott, C. 2004. Polymer alloys of nodax copolymers and poly(lactic acid). Macromolecular Bioscience 4 269-275. 

Rasal, R.M., Janorkar, A.V. and Hirt, D.E. 2010. Poly(lactic acide) modifications. Progress in Polymer Science 33 338-356. 

Xu, Y. and Qu, J. 2009. Mechanical and rheological properties of epoxidized soybean oil plasticized poly(lactic acid). Journal of Applied Polymer Science 112 3185 - 3191. 

Biopolymers conventionally and chemically synthesised and the monomers are obtained from agro-resources, e.g., the poly-lactic acids or PL As... 

Hydrocortisone microspheres (108,109) and films (110) based on poly(lactic acid) have been investigated. A cage implant technique was used to study the performance of monolithic poly (DL-lactide) films loaded with hydrocortisone acetate (110). Films 1.5 x 0.6 cm were inserted into titanium wire-mesh cages 3.5 x 1.0 cm. The cages were implanted in the backs of rats and the inflammatory exudate was sampled periodically. The white cell concentration in the samples was lower than that of controls at all times during the 21-day test. 

Gilding, D. K., and Reed, A. M., Biodegradable polymers for use in surgery poly(glycolic)/poly(lactic acid) homo- and copolymers 1, Polymer. 20. 1459, 1979. 

T., Katutani, Y., and Kitsugi, T., Release of antibiotics from composites of hydroxyapatite and poly(lactic acid), in Advances in Drug Delivery Systems (J. M. Anderson and S. W. Kim, eds.), Elsevier, New York, 1986, pp. 179-186. 

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