Production of Lactide

Biodegradable plastics based on lactic acid have been available on a small scale for many years. They have been used In applications such as medical implants, but their high price was a deterrent to widespread use in lower value applications such as packaging. However, new technologies for production of lactide monomers greatly lowered costs, making the polymers much more competitive. Generally, the lactic acid is obtained from corn or other biobased materials by a fermentation process, and then chemical synthesis is used to produce the polymer from the lactic acid or lactide monomers. 

Ingeo PLA is easily processable and suitable as amorphous biopackaging material as a result of its relatively high meso-lactide content. The downside is the poor resistance to elevated temperatures (low heat distortion temperature, HDT) during transportation, storage, and use of articles produced from this bioplastic. mc o-Lactide— which contains an L- and a D-isomer—is an unavoidable side product of lactide production and must be separated from L- and D-lactides of high stereochemical purity. 

The LCA process takes into account all of the energy, raw materials, water, and fossil fuels required in the production of Ingeo pellets. The first step is the harvesting of the corn in the fields where the corn is grown, harvested, dried, and transported to the com wet mill. The process requires fertilizers, electricity, fossil fuels, natural gas, and other materials. The second step is the production of starches and dextrose sugars with the use of fossil fuels, electricity, steam, water, and other materials. The third step is the fermentation to lactic acid with the use of electricity, fossil fuels, water, steam, and other materials. The fourth step is the production of lactide from lactic acid with the use of fossil fuels, electricity, steam, water, and other materials. The last step is the polymerization of polylactide and conversion into PLA pellets with the use of electricity, fossil fuels, water, and other materials. 

Although the straight dehydration of lactic acid does not produce high molecular weight polymers, the process is important in the production of lactide, as noted above. The amount of lactide produced is influenced by temperature. 

Production of lactide from corn according to the Dow-Cargill process. 

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. 

Fabrication of drug-containing fibers is a natural progression when one considers the extensive history of lactide/glycolides in suture applications. The lactide/glycolide polymers are easily melt-spun into mono- or multifilament products at relatively low temperatures. 

Sterilization of the finished drug delivery formulation is an important consideration often overlooked in the early design of lactide/glycolide delivery systems. Aseptic processing and terminal sterilization are the two major routes of affording an acceptably sterile product. Both of these methods are suitable for products based on lactide/glycolide polymers if proper care is exercised in processing or selection of the treatment procedures. 

Zinc compounds have recently been used as pre-catalysts for the polymerization of lactides and the co-polymerization of epoxides and carbon dioxide (see Sections 2.06.8-2.06.12). The active catalysts in these reactions are not organozinc compounds, but their protonolyzed products. A few well-defined organozinc compounds, however, have been used as co-catalysts and chain-transfer reagents in the transition metal-catalyzed polymerization of olefins. 

There microspheres were prepared from a solution of Resomer RG756 (copolymer of o -lactide and glycohde, 75% 25%, product of Boehringer, Germany) in CH2CI2 using Mini Spray Dryer 190 (Biichi, Switzerland). 

The successful utilization of alkoxo Zn- and Mg-tris(pyrazolyl) borate initiators in the lactide polymerization inspired the synthesis of sterically bulky B-diketiminates (BDls) (Fig. 5) and their zinc and magnesium derivatives [60-62]. Replacing the ancillary ligands resulted in the production of several mono- and dinuclear complexes of Mg" and Zn" 24-39 (Fig. 6), which demonstrated excellent catalytic activity for the polymerization of l- and rac-lactide [62-66]. 

Titanium alkoxides are also effective and sought-after initiators for the ROP of lactides due to a low toxicity, which minimizes the problems linked to the presence of catalyst residues in commercial PLA products [18, 19]. Despite impressive advancements in the use of Lewis acidic metal initiators in the preparation of PLAs, surprisingly little attention has been paid to the group 4 metal (Ti, Zr, Hf) initiators, probably due to the highly oxophilic nature of M(1V) which has a natural tendency to form aUcoxy-bridged multinuclear complexes. Verkade and coworkers previously demonstrated a series of titanium aUcoxide complexes 118-122 (Fig. 17) that function as moderately efficient initiators in bulk homopolymeization of L-lactide and rac-lactide, some of these initiators displaying a well-controlled polymerization behavior [119]. 

A photoreactive macromer consisting of the reaction product of poly(capro-lactone-co-lactide) and pentaerythritol ethoxylate was prepared by Chudzik et al. (3) and used as tissue implants. 

Lactamide has been prepared by the action of gaseous ammonia on ethyl lactate 3 and from lactic anhydride 4 and gaseous ammonia. It has been made also by the action of ammonia gas on lactide.5 The amide was obtained in excellent yields by treatment of the acetone condensation product of lactic acid with ammonia.6 Amides have been prepared by the reaction of liquid ammonia with esters at temperatures varying from — 330 to... 

---