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 composition comprising poly(glycerol sebacate) urethane, wherein the poly(glycerol sebacate) urethane is formed from a poly(glycerol sebacate) resin reacted with an isocyanate at an isocyanate-to-hydroxyl stoichiometric ratio in the range of 1:0.25 to 1:1.25.
2. The composition of claim 1 , wherein the poly(glycerol sebacate) resin has a molecular weight greater than 10,000 Da.
3. The composition of claim 1 , wherein the poly(glycerol sebacate) resin has a polydispersity index less than 12.
4. The composition of claim 1 , wherein the poly(glycerol sebacate) resin has a glycerol-to-sebacic acid stoichiometric ratio of between 1:0.5 and 1:1.5.
5. The composition of claim 1 , wherein the isocyanate is a blocked isocyanate.
6. The composition of claim 1 , wherein the composition is free of a solvent.
7. The composition of claim 1 further comprising an active pharmaceutical ingredient mixed with the poly(glycerol sebacate) urethane, wherein the active pharmaceutical ingredient is at least 10% w/w of the composition.
8. The composition of claim 1 , wherein the isocyanate-to-hydroxyl stoichiometric ratio is in the range of 1:0.25 to 1:1.
9. The composition of claim 1 further comprising at least one additive mixed with the poly(glycerol sebacate) urethane, wherein the at least one additive is at least 10% w/w of the composition and the at least one additive is selected from the group consisting of an active pharmaceutical ingredient, a filler, and a combination thereof.
10. A composition comprising poly(glycerol sebacate) urethane, wherein the poly(glycerol sebacate) urethane is formed from a poly(glycerol sebacate) resin having a polydispersity index in the range of 8 to less than 12.
11. The composition of claim 10 , wherein the poly(glycerol sebacate) resin has a molecular weight greater than 10,000 Da.
12. The composition of claim 10 , wherein the poly(glycerol sebacate) resin has a glycerol-to-sebacic acid stoichiometric ratio of between 1:0.5 and 1:1.5.
13. The composition of claim 10 , wherein the isocyanate is a blocked isocyanate.
14. The composition of claim 10 , wherein the composition is free of a solvent.
15. The composition of claim 10 , wherein the isocyanate-to-hydroxyl stoichiometric ratio is in the range of 1:0.25 to 1:1.25.
16. The composition of claim 10 further comprising an active pharmaceutical ingredient mixed with the poly(glycerol sebacate) urethane, wherein the active pharmaceutical ingredient is at least 10% w/w of the composition.
17. A process of forming a poly(glycerol sebacate) urethane, the process comprising:
homogeneously mixing a flowable poly(glycerol sebacate) resin with a catalyst and a solvent 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 a composition comprising the isocyanate to form a reaction mixture; and
dispensing the reaction mixture to form the poly(glycerol sebacate) urethane.
18. The process of claim 17 , wherein the weight average molecular weight of the flowable poly(glycerol sebacate) resin is greater than 10,000 Da.
19. The process of claim 17 , wherein the homogeneously combining comprises mixing in a mixing chamber, a tip, or a nozzle.
20. The process of claim 17 , wherein the resin blend and the composition comprising the isocyanate are physically separated in a dual-barrel cartridge prior to the homogeneously combining.
21. The process of claim 17 , wherein the dispensing comprises spraying the reaction mixture through a spray coater nozzle.
22. The process of claim 17 , wherein the dispensing coats a substrate.
23. The process of claim 22 , wherein the substrate is a textile.
24. The process of claim 22 , wherein the dispensing comprises spraying the reaction mixture onto the substrate to spray coat the substrate.
25. The process of claim 17 , wherein the dispensing comprises spraying into air to form microparticles of the poly(glycerol sebacate) urethane.
26. A composition comprising poly(glycerol sebacate) urethane and an active pharmaceutical ingredient mixed with the poly(glycerol sebacate) urethane, wherein the poly(glycerol sebacate) urethane is formed from a poly(glycerol sebacate) resin reacted with an isocyanate at an isocyanate-to-hydroxyl stoichiometric ratio in the range of 1:0.25 to 1:5 and the active pharmaceutical ingredient mixed with the poly(glycerol sebacate) urethane is at least 40% w/w of the composition.
27. The composition of claim 26 , wherein the poly(glycerol sebacate) resin has a molecular weight greater than 10,000 Da.
28. The composition of claim 26 , wherein the poly(glycerol sebacate) resin has a polydispersity index less than 12.
29. The composition of claim 26 , wherein the poly(glycerol sebacate) resin has a glycerol-to-sebacic acid stoichiometric ratio of between 1:0.5 and 1:1.5.
30. The composition of claim 26 , wherein the isocyanate is a blocked isocyanate.
31. The composition of claim 26 , wherein the composition is free of a solvent.
32. A composition comprising poly(glycerol sebacate) urethane and at least one additive mixed with the poly(glycerol sebacate) urethane, wherein the poly(glycerol sebacate) urethane is formed from a poly(glycerol sebacate) resin reacted with an isocyanate at an isocyanate-to-hydroxyl stoichiometric ratio in the range of 1:0.25 to 1:5, the at least one additive is at least 40% w/w of the composition, and the at least one additive is selected from the group consisting of an active pharmaceutical ingredient, a filler, and a combination thereof.