Tunable, controlled-release, urethane-containing elastomers and processes of forming the same
A process forms an implantable product including poly(glycerol sebacate) urethane (PGSU) loaded with an active pharmaceutical ingredient (API). The process includes homogeneously mixing a flowable poly(glycerol sebacate) (PGS) resin with the API and a catalyst to form a resin blend. The process also includes homogeneously combining the resin blend with an isocyanate to form a reaction mixture and injecting the reaction mixture to form the PGSU loaded with the API. An implantable product includes a PGSU loaded with an API. In some embodiments, the implantable product includes at least 40% w/w of the API, and the implantable product releases the API by surface degradation of the PGSU at a predetermined release rate for at least three months under physiological conditions. In some embodiments, the PGSU is formed from a PGS reacted with an isocyanate at an isocyanate-to-hydroxyl stoichiometric (crosslinking) ratio in the range of 1:0.25 to 1:1.25.
1. A process of forming an implantable product comprising poly(glycerol sebacate) urethane loaded with an active pharmaceutical ingredient, the process comprising:
homogeneously mixing a flowable poly(glycerol sebacate) resin with the active pharmaceutical ingredient and a catalyst to form a resin blend;
selecting an amount of isocyanate such that an isocyanate-to-hydroxyl stoichiometric ratio is in the range of 1:0.25 to 1:1.25;
homogeneously combining the resin blend with the isocyanate to form a reaction mixture; and
injecting the reaction mixture to form the poly(glycerol sebacate) urethane loaded with the active pharmaceutical ingredient.
2. The process of claim 1 , wherein the weight average molecular weight of the flowable poly(glycerol sebacate) resin is greater than 10,000 Da.
3. The process of claim 1 , wherein the homogeneous combining comprises shear mixing.
4. The process of claim 1 , wherein the injecting comprises reaction injection molding.
5. The process of claim 1 , wherein the process occurs at a temperature of 60° C. or less.
6. The process of claim 1 , wherein the injecting comprises injecting the reaction mixture into a mold.
7. The process of claim 1 further comprising crosslinking the poly(glycerol sebacate) urethane loaded with the active pharmaceutical ingredient for up to 24 hours at up to 40° C. to form the implantable product.
8. The process of claim 1 , wherein the injecting the reaction mixture comprises an additive manufacturing process to form the implantable product.
9. The process of claim 1 , wherein the formed poly(glycerol sebacate) urethane is blended with a thermoplastic or an elastomer.
10. An implantable product comprising a poly(glycerol sebacate) urethane loaded with an active pharmaceutical ingredient, wherein the poly(glycerol sebacate) urethane is formed from a poly(glycerol sebacate) reacted with an isocyanate at an isocyanate-to-hydroxyl stoichiometric ratio is in the range of 1:0.25 to 1:1.25.
11. The implantable product of claim 10 , wherein the poly(glycerol sebacate) urethane is formed from a poly(glycerol sebacate) resin having a molecular weight greater than 10,000 Da.
12. The implantable product of claim 10 , wherein the poly(glycerol sebacate) urethane is formed from a poly(glycerol sebacate) resin having a polydispersity index less than 12.
13. The implantable product of claim 10 , wherein the poly(glycerol sebacate) urethane is formed from a poly(glycerol sebacate) resin having a glycerol-to-sebacic acid stoichiometric ratio of between 1:0.5 and 1:1.5.
14. The implantable product of claim 10 , wherein the isocyanate is a blocked isocyanate.
15. A process of forming a product comprising poly(glycerol sebacate) urethane, the process comprising:
homogeneously mixing a flowable poly(glycerol sebacate) resin with a catalyst to form a resin blend;
selecting an amount of isocyanate such that an isocyanate-to-hydroxyl stoichiometric ratio is in the range of 1:0.25 to 1:1.25;
homogeneously combining the resin blend with the isocyanate to form a reaction mixture; and
injecting the reaction mixture to form the poly(glycerol sebacate) urethane;
wherein the process further comprises removing generated gasses, entrained gasses, entrapped gasses, or combinations thereof.
16. The process of claim 15 , wherein the removing occurs under vacuum.
17. The process of claim 15 , wherein the removing occurs under sonication.
18. A process of forming a product comprising poly(glycerol sebacate) urethane, the process comprising:
homogeneously mixing a flowable poly(glycerol sebacate) resin with a catalyst to form a resin blend;
selecting an amount of isocyanate such that an isocyanate-to-hydroxyl stoichiometric ratio is in the range of 1:0.25 to 1:1.25;
homogeneously combining the resin blend with the isocyanate to form a reaction mixture; and
injecting the reaction mixture to form the poly(glycerol sebacate) urethane;
wherein the resin blend includes no more than 50% w/w of a solvent.
19. The process of claim 18 further comprising evaporating the solvent from the poly(glycerol sebacate) urethane at a temperature of up to 40° C. for up to 6 days.
20. The process of claim 18 , wherein the homogeneous mixing occurs in the absence of a solvent.
21. The process of claim 18 , wherein the flowable poly(glycerol sebacate) resin is free of a solvent.
22. The process of claim 18 , wherein the injecting comprises spray coating the reaction mixture.
23. The process of claim 18 , wherein the isocyanate-to-hydroxyl stoichiometric ratio is in the range of 1:0.25 to 1:1.
24. The process of claim 23 , wherein the isocyanate-to-hydroxyl stoichiometric ratio is in the range of 1:0.25 to 1:0.75.
25. The process of claim 1 , wherein the injecting comprises spray coating the reaction mixture.
26. The process of claim 1 , wherein the poly(glycerol sebacate) resin has a polydispersity index in the range of 8 to less than 12.
27. The process of claim 1 , wherein the isocyanate-to-hydroxyl stoichiometric ratio is in the range of 1:0.25 to 1:1.
28. The process of claim 27 , wherein the isocyanate-to-hydroxyl stoichiometric ratio is in the range of 1:0.25 to 1:0.75.
29. The implantable product of claim 10 , wherein the isocyanate-to-hydroxyl stoichiometric ratio is in the range of 1:0.25 to 1:1.
30. The implantable product of claim 29 , wherein the isocyanate-to-hydroxyl stoichiometric ratio is in the range of 1:0.25 to 1:0.75.