RESOMER^® Biodegradable Polymers for Medical Device Applications Research

Biodegradable Polymers: RESOMER^® Materials by Evonik Röhm GmbH

• RESOMER^® Product Table
• Properties of PLA/PGA Polymers
• End Groups
• Consistency

Introduction

Polymers with controlled biomedical degradation characteristics can be used as an important part of tissue engineering and drug delivery therapies. Many types of natural and synthetic biodegradable polymers have been investigated for medical and pharmaceutical applications. While use of natural polymers, such as cellulose and starches, is still common in biomedical research, synthetic biodegradable polymers are increasingly used in pharmaceutical and tissue-engineering products. Synthetic polymers can be prepared with chemical structures tailored to optimize physical properties of the biomedical materials and with well-defined purities and compositions superior to those attainable when using natural polymers. There are now several established chemical classes of synthetic biodegradable polymers that offer good biocompatibility and can be selected to tune rates of biodegradation and mechanical strength.¹

Poly(glycolic acid) (PGA), Poly(lactic acid) (PLA) and their copolymers have been researched for a wider range of applications than any other type of biodegradable polymers. PLA/PGA are biodegradable polyesters that degrade in the body by simple hydrolysis of the ester backbone to non-harmful and non-toxic compounds. The degradation products are either excreted by the kidneys or eliminated as carbon dioxide and water through well-known biochemical pathways. Current applications of the polymers include surgical sutures and resorbable implants, with significant interest to further expand the use of these materials to drug encapsulation and delivery applications. Since PLA/PGA polymers are considered safe, non-toxic and biocompatible by regulatory agencies in virtually all developed countries, additional applications of these materials can be brought to market sooner and are more cost effective than those utilizing novel polymers with unproven biocompatibility.

We are pleased to offer a comprehensive selection of PLA/PGA RESOMER^® polymers manufactured by Evonik Röhm Pharma GmbH. Below you will find basic information about properties of the RESOMER^® polymers and a product table listing available RESOMER^® products. RESOMER^® polymers from our catalog are sold for research and development applications only. Chemically identical GMP materials are available directly from Evonik Röhm GmbH.

Table 1 RESOMER® Biodegradable Polymers

Product No.	RESOMER Type	Product Name	Molecular Weight Range	Viscosity [dl/g]	Application	Tg [°C]	Tm [°C]	End Group
719854	RESOMER L 206 S	Poly(L-lactide)	--	0.8-1.2	Medical Device	60-65	180-185	ester terminated
719951	RESOMER R 202 S	Poly(D,L-lactide)	10,000- 18,000	0.16-0.24	Controlled Release	38-42	amorphous	ester terminated
719978	RESOMER R 202 H	Poly(D,L-lactide)	10,000- 18,000	0.16-0.24	Controlled Release	44-48	amorphous	free carboxylic acid
719935	RESOMER R 203 S	Poly(D,L-lactide)	18,000- 28,000	0.25-0.35	Controlled Release	46-50	amorphous	ester terminated
719943	RESOMER R 203 H	Poly(D,L-lactide)	18,000- 28,000	0.25-0.35	Controlled Release	48-52	amorphous	free carboxylic acid
719889	RESOMER RG 502	Poly(D,L-lactide-co-glycolide) 50:50	7,000- 17,000	0.16-0.24	Controlled Release	42-46	amorphous	alkyl ester
719897	RESOMER RG 502 H	Poly(D,L-lactide-co-glycolide) 50:50	7,000- 17,000	0.16-0.24	Controlled Release	42-46	amorphous	free carboxylic acid
739952	RESOMER RG 503	Poly(D,L-lactide-co-glycolide) 50:50	24,000 - 38,000	0.32-0.44	Controlled Release	44-48	amorphous	ester
719870	RESOMER RG 503 H	Poly(D,L-lactide-co-glycolide) 50:50	24,000- 38,000	0.32-0.44	Controlled Release	44-48	amorphous	free carboxylic acid
739944	RESOMER RG 504	Poly(D,L-lactide-co-glycolide) 50:50	38,000 - 54,000	0.45-0.60	Controlled Release	46-50	amorphous	ester
719900	RESOMER RG 504 H	Poly(D,L-lactide-co-glycolide) 50:50	38,000- 54,000	0.45-0.60	Controlled Release	46-50	amorphous	free carboxylic acid
739960	RESOMER RG 505	Poly(D,L-lactide-co-glycolide) 50:50	54,000 - 69,000	0.61-0.74	Controlled Release	48-52	amorphous	ester
719862	RESOMER RG 653 H	Poly(D,L-lactide-co-glycolide) 65:35	24,000- 38,000	0.32-0.44	Controlled Release	46-50	amorphous	free carboxylic acid
719919	RESOMER RG 752 H	Poly(D,L-lactide-co-glycolide) 75:25	4,000- 15,000	0.14-0.22	Controlled Release	42-46	amorphous	free carboxylic acid
719927	RESOMER RG 756 S	Poly(D,L-lactide-co-glycolide) 75:25	76,000- 116,000	0.71-1.0	Controlled Release	49-55	amorphous	ester terminated
739979	RESOMER RG 858 S	Poly(D,L-lactide-co-glycolide) 85:15	190,000 - 240,000	1.3-1.7	Controlled Release	-	amorphous	alkyl ether
719846	RESOMER X	Polydioxanone	--	1.5-2.2 (0.1% in HFIP, 30ºC)	Medical Device	(‑10)‑(‑5)	110-115	--
769754	Resomer C 212	Poly(caprolactone)	-	1.13-1.38	Medical Device and Tissue Engineering		56-84	easter
769762	Resomer C 209	Poly(caprolactone)	-	0.8-1.0	Medical Device and Tissue Engineering		56-84	easter
769940	Resomer L 207 S	Poly(L-lactide)	-	1.5-2.0	Medical Device and Tissue Engineering	60-65	-	easter
769851	Resomer LC 703 S	Poly(L-lactide-co-ε-caprolactone) 70:30	-	1.3-1.8	Medical Device and Tissue Engineering	162-169	-	easter
769894	Resomer LG 824 S	Poly(L-lactide-co-glycolide) 82:18	-	1.7-2.6	Medical Device and Tissue Engineering	54-60	157-164	easter
769886	Resomer LG 855 S	Poly(L-lactide-co-glycolide) 85:15	-	2.5-3.5	Medical Device and Tissue Engineering	53-63	159-166	easter
769878	Resomer LG 857 S	Poly(L-lactide-co-glycolide) 85:15	-	5.0-7.0	Medical Device and Tissue Engineering	53-64	159-166	easter
769916	Resomer LR 704 S	Poly(L-lactide-co-D,L-lactide), 70:30	-	2.0-2.8	Medical Device and Tissue Engineering	56-62	102-111	easter
769908	Resomer LR 706 S	Poly(L-lactide-co-D,L-lactide), 70:30	-	3.3-4.3	Medical Device and Tissue Engineering	56-62	102-111	easter
769959	Resomer LR 706 S	Poly(L-lactide-co-D,L-lactide), 70:38	-	5.7-6.5	Medical Device and Tissue Engineering	56-62	102-111	easter
769835	Resomer R 205 S	Poly(D,L-lactide)	-	0.55-0.75	Controlled Release	-	amorphous	easter
769843	Resomer R 207 S	Poly(D,L-lactide)	-	1.3-1.7	Controlled Release	-	amorphous	easter
769770	Resomer RG 750 S	Poly(D,L-lactide-co-glycolide) 75:25	-	0.8-1.2	Controlled Release	-	amorphous	easter
769827	Resomer RG 752 S	Poly(D,L-lactide-co-glycolide) 75:25	-	0.16-0.24	Controlled Release	44-50	amorphous	easter
769819	Resomer RG 753 H	Poly(D,L-lactide-co-glycolide) 75:25	-	0.32-0.44	Controlled Release	44-50	amorphous	easter
769800	Resomer RG 753 S	Poly(D,L-lactide-co-glycolide) 75:25	-	0.32-0.44	Controlled Release	44-50	amorphous	easter
769797	Resomer RG 755 S	Poly(D,L-lactide-co-glycolide) 75:25	-	0.5-0.7	Controlled Release	48-54	amorphous	easter
769789	Resomer RG 757 S	Poly(D,L-lactide-co-glycolide) 75:25	-	0.9-1.3	Controlled Release	-	amorphous	easter

Properties of PLA/PGA Polymers

PGA, PLA and their copolymers are some of the most frequently used biodegradable polymer materials in part because their properties that can be tuned by changing the polymer composition within the basic PLA/PGA theme. The following classes of RESOMER polymers are available in our catalog:

Figure 1. General Structure of PGA

Poly(glycolic acid) (PGA)

PGA (457620) is a highly crystalline material, which boasts a high melting point (225-230 °C) and variable solubility in organic solvents that is generally low and depends on polymer molecular weight. It is still susceptible to hydrolysis due to the ester bond in the polymer backbone. In spite of its low solubility, this polymer has been fabricated into a variety of forms and structures. Techniques used to develop PGA-based structures include extrusion, injection and compression molding as well as particulate leaching and solvent casting. Fibers of PGA have a high strength and modulus (7 GPa) and are particularly rigid,² which has promoted investigation to their use in bone internal fixation devices. However, lower solubility and brittle nature of PGA materials can limit their utility in some applications.

Figure 2. General Structure of PLA

Poly(lactic acid) (PLA)

Unlike glycolide, lactide is a chiral molecule and exists in two distinct optically active forms – L-lactide and D-lactide. When each of these monomers is polymerized, the resulting polymer is semi-crystalline. Polymerization of a racemic mixture of L- and D-lactides forms poly-D,L-lactide (PDLLA), which is amorphous and has a glass transition temperature of 55-60 °C. The degree of crystallinity can be tuned by altering the ratio of D to L enantiomers within the polymer. Selection of the PLA stereochemistry can have a major effect on the polymer properties, processability and biodegradability. Poly (L-lactide) or PLLA is often the polymer of choice for cast/extruded biomedical devices because it breaks down into L(+)-lactic acid units, which is the naturally occurring stereoisomer and is therefore excreted with minimal toxicity.³

Figure 3. General Structure of PLA: PGA copolymer

Poly (Lactide-co-Glycolide) Copolymers (PLGA)

Among the co-polyesters investigated, extensive research has been performed in developing a full range of PLGA polymers. Both L- and DL-lactides have been used for co-polymerization. The ratio of glycolide to lactide at different compositions allows control of the degree of crystallinity of the polymers.⁴ When the crystalline PGA is co-polymerized with PLA, the degree of crystallinity is reduced and as a result this leads to increases in rates of hydration and hydrolysis. It can therefore be concluded that the degradation time of the copolymer is related to the ratio of monomers used in synthesis. In general, the higher the content of glycolide, the quicker the rate of degradation. However, an exception to this rule is the 50:50 ratio of PGA: PLA, which exhibits the fastest degradation.^5,6

Figure 4. General Structure of Polydioxanone

Polydioxanone (PDS)

Although biodegradable polylactides and glycolides have been used to develop versatile resorbable multi-filament structures, there is growing research involved in the development of materials that form monofilament sutures. Multifilament sutures have a higher risk of infection associated with their use and cause a greater amount of friction when penetrating tissues.^7,8 Polydioxanone (referred to as PDS) is made by a ring-opening polymerization of thep-dioxanone monomer. It is characterized by a glass transition temperature in the range of –10 to 0 °C and a degree of crystallinity of about 55%. Materials prepared with PDS show enhanced flexibility due to the presence of an ether oxygen within the backbone of the polymer chain. When used in vivo, it degrades into monomers with low toxicity and also has a lower modulus than PLA or PGA. For the production of sutures, PDS is generally extruded into fibers at the lowest possible temperature, in order to avoid its spontaneous depolymerization back to the monomer.

End Groups

The RESOMER^® materials offered in our catalog are available with three types of end-groups functions: (i) free carboxylic acid group, (ii) ester terminated group, (iii) alkyl ester group. Polymers capped with ester terminated and alkyl ester groups typically show longer degradation lifetimes than the free carboxylic analogs. ⁹ This choice in end group provides a range of PLA/PGA materials with distinctive properties to suit your individual research needs.

Quality and Specifications of RESOMER Polymers

All RESOMER^® polymers are made by Evonik Röhm GmbH and will conform to a rigid set of pre-determined specifications in order to ensure that the material has consistent properties for the entire process, from research through commercialization. Examples of specifications that you may find useful include:

• Residual Monomers
• Inherent Viscosity
• Heavy Metal Content
• Sulfated Ash Content

In addition to the new RESOMER^® products, we offer an extensive line of other synthetic biodegradable and natural polymers.

References

1. Ratner B, Hoffman A, Schoen F, Lemons J. 2004. Biomaterials Science. 2. London: Elsevier .

2. Middleton J, Tipton A. 1998. Medical Plastic and Biomaterials . 30.

3. Athanasiou K. 1996. Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid/ polyglycolic acid copolymers. Biomaterials. 17(2):93-102. https://doi.org/10.1016/0142-9612(96)85754-1

4. Cohn D, Younes H, Marom G. 1987. Amorphous and crystalline morphologies in glycolic acid and lactic acid polymers. Polymer. 28(12):2018-2022. https://doi.org/10.1016/0032-3861(87)90035-8

5. Park TG, Lu W, Crotts G. 1995. Importance of in vitro experimental conditions on protein release kinetics, stability and polymer degradation in protein encapsulated poly (d,l-lactic acid-co-glycolic acid) microspheres. Journal of Controlled Release. 33(2):211-222. https://doi.org/10.1016/0168-3659(94)00084-8

6. Miller RA, Brady JM, Cutright DE. 1977. Degradation rates of oral resorbable implants (polylactates and polyglycolates): Rate modification with changes in PLA/PGA copolymer ratios. J. Biomed. Mater. Res.. 11(5):711-719. https://doi.org/10.1002/jbm.820110507

7. Krukowski ZH, Cusick EL, Engeset J, Matheson NA. 1987. Polydioxanone or polypropylene for closure of midline abdominal incisions: A prospective comparative clinical trial. Br. J. Surg.. 74(9):828-830. https://doi.org/10.1002/bjs.1800740927

8. Schoetz DJ. 1988. Closure of Abdominal Wounds With Polydioxanone. Arch Surg. 123(1):72. https://doi.org/10.1001/archsurg.1988.01400250082015

9. Houchin M, Topp E. 2008. Chemical Degradation of Peptides and Proteins in PLGA: A Review of Reactions and Mechanisms. Journal of Pharmaceutical Sciences. 97(7):2395-2404. https://doi.org/10.1002/jps.21176