Lactide Manufacturing

In the past two decades, several papers have appeared on lactide manufacture [73, 74]. A main underlying problem in understanding all information is that the reaction from oligomer to lactide is an equilibrium reaction. In order to pull the reaction toward the right, lactide must be withdrawn from the system. In reaction engineering terms, this means that the chemical kinetics of the reaction cannot be understood without consideration of the method and efficiency of lactide removal. In terms of know-how described in patents, this means that reported lactide production rates depend to a large extent on the geometry of the equipment in which lactide synthesis is performed and that provides for removal of lactide vapor from the reaction zone. 

FIGURE 1.7 Schematic illustration of lactide manufacture by thermal catalytic depolymerization of lactic acid oligomers. 

The generally applied ROP process for polylactides involves three separate steps polycondensation, lactide manufacturing, and ring-opening polymerization (Figure 3.1). All three chemical processes have basically been known for a long... 

The lactide manufacturing is done by depolymerization of PLA that preferably is in the range of 400-2500 g/... 

The crystallinity of poly(lactide- (9-glycoHde) samples has been studied (36). These copolymers are amorphous between the compositional range of 25—70 mol % glycoHde. Pure polyglycoHde was found to be about 50% crystalline whereas pure poly-L-lactide was about 37% crystalline. An amorphous poly(L-lactide-i (9-glycoHde) copolymer is used in surgical cHps and staples (37). The preferred composition chosen for manufacture of cHps and staples is the 70/30 L-lactide/glycoHde copolymer. 

Braided Synthetic Absorbable Sutures. Suture manufacturers have searched for many years to find a synthetic alternative to surgical gut. The first successful attempt to make a synthetic absorbable suture was the invention of polylactic acid [26023-30-3] suture (15). The polymer was made by the ring-opening polymerization of L-lactide [95-96-5] (1), the cycUc dimer of L-lactic acid. 

Lactide polymers, manufacture of, 14 122 Lactisole, 24 246 Lactitol, 12 40 Lactobacillic acid, 5 36t Lactobacillus, 12 478 Lactococcus, 12 478 Lactoferrins, 18 258 Lactones, 10 497 12 663-664 aroma chemicals, 3 256 in beer, 3 582t Lactonitrile, 8 174 Lactonization, 10 499... 

The biodegradable polymer available in the market today in largest amounts is PEA. PEA is a melt-processible thermoplastic polymer based completely on renewable resources. The manufacture of PEA includes one fermentation step followed by several chemical transformations. The typical annually renewable raw material source is com starch, which is broken down to unrefined dextrose. This sugar is then subjected to a fermentative transformation to lactic acid (LA). Direct polycondensation of LA is possible, but usually LA is first chemically converted to lactide, a cyclic dimer of LA, via a PLA prepolymer. Finally, after purification, lactide is subjected to a ring-opening polymerization to yield PLA [13-17]. 

Gruber PR, Hall ES, Kolstad JJ, Iwen ML, Benson RD, Borchardt RL (1994) Continuous process for manufacture of lactide polymers with purification by distillation. US Patent 5357035... 

Jain, R. A. (2000), The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices, Biomaterials, 21(23), 2475-2490. 

One of the most highly developed biopolymers is poly (lactic acid) (PLA). In the USA, PLA is manufactured by NatureWorks at a plant in Nebraska using lactic acid derived from corn. (Lactic acid can also be obtained from other natural sources such as wheat or potatoes.) Poly (lactic acid) is produced by ring opening polymerization of the lactide, as shown in Figure 8.12. 

Microspheres Intramuscular injections comprising a microsphere formulation manufactured from poly(DL-lactide) have been described for veterinary applications. Microspheres have been formulated to deliver progesterone (1.25 g) and estradiol (100 mg) continuously for a duration of 12 to 14 days. Other microsphere products have been developed, which contain various active ingredients including ivermectin, estradiol, moxidectin, and vitamin B12. 

A scientific breakthrough in order to design USCAs on demand can be seen in the third generation (Myomap, Quantison, BiSphere and Sonavist). Compared to the more or less free bubbles of the first and second generations, the novel type of USCAs consist of encapsulated microbubbles with a shell formed by a biopolymer (like human albumin) and/or a biocompatible synthetic polymer (like copolymers of poly-lactide and polyglycolide or derivatives of polycyanoacrylate). In addition to the prolongation of the lifetime in the blood stream, these polymer-stabilized microbubbles can be manufactured to fulfill certain needs, and to interact with diagnostic ultrasound in a defined and optimal manner. 

The first synthetic absorbable suture was made from a homopolymer of glycolic acid by Davis Geek Co. and manufactured with the tradename Dexon (1970). This suture was followed by a second material produced by Ethicon, Inc., in 1974, a copolymer of lactide and glycolide known as poly-glactine 910 or Vicryl. Both Vicryl and Dexon are made from polymer fibers, which are braided to produce sutures. In addition. Vicryl is Teflon coated for... 

P. Gruber, E. Hall, J. Kolstad, M. Iwen, R. Benson, and R. Borchardt, Continuous process for manufacture of lactide polymers with controlled optical purity US 5,142,023, assigned to Cargill, Incorporated (Minnetonka, MN), 1992. 

GRO 10] Groot W., Boren T., Lifecycle assessment of the manufacture of lactide and PLA biopolymers from sugarcane in Thailand , International Journal of LifeCycle Assessment, vol. 15, p. 970, 2010. 

Sansdrap P, Moes AJ. Influence of manufacturing parameters on the size characteristics and the release profiles of nifedipine from poly(DL-lactide-co-glycolide) microspheres. International Journal of Pharmaceutics. 1993 98 157-164. 

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