Post-processing of a medical device to control morphology and mechanical properties
View Patent ↗A method of forming a coated medical device is described in which a coating including a therapeutic agent dispersed in a polymer or oligomer matrix is applied to an outer surface of the medical device. The coating is then post-processed to selectively remove a substantial portion of the polymer or oligomer matrix from the coating. The post-processed coating is then sterilized.
1. A method of forming a coated medical device comprising:
applying a coating to an outer surface of a medical device, the coating including a therapeutic agent dispersed in a matrix of a polymer or oligomer excipient;
post-processing the medical device by immersion in a solvent or solution, thereby selectively removing a substantial portion of the polymer or oligomer excipient from the matrix in which the therapeutic agent is dispersed; and
sterilizing the post-processed medical device,
wherein the coating comprises less than 50% by weight of the therapeutic agent prior to post-processing, and the coating comprises greater than 50% by weight of the therapeutic agent after post-processing.
2. The method of claim 1 , wherein the therapeutic agent is substantially water insoluble.
3. The method of claim 2 , wherein the coating comprises 35% or less by weight of the therapeutic agent prior to post-processing, and the coating comprises 65% or more by weight of the therapeutic agent after post-processing.
4. The method of claim 2 , wherein less than 10% by weight of the therapeutic agent is removed from the coating during post-processing.
5. The method of claim 4 , wherein greater than 75% by weight of the polymer or oligomer excipient is removed from the coating during post-processing.
6. The method of claim 2 , wherein less than 15% by weight of therapeutic agent is removed from the coating during post-processing.
7. The method of claim 6 , wherein greater than 90% of the polymer or oligomer excipient is removed from the coating during post-processing.
8. The method of claim 2 , wherein the substantially water insoluble therapeutic agent comprises a taxane.
9. The method of claim 8 , wherein the taxane is selected from the group consisting of pactlitaxel, paclitaxel analogues, and paclitaxel derivatives thereof.
10. The method of claim 1 , wherein applying the coating comprises dip coating an expandable portion of the medical device in a solution comprising:
paclitaxel;
iodine;
a polymer; and
solvent.
11. The method of claim 10 , wherein the polymer is soluble in both water, and a solvent solution comprising an organic solvent and less than 20% by weight water.
12. The method of claim 10 , wherein the polymer has a molecular weight below 20,000 Daltons.
13. The method of claim 12 , wherein the polymer is polyethylene glycol (PEG).
14. The method of claim 13 , wherein the solvent comprises a mixture of ethanol and acetonitrile.
15. The method of claim 2 , wherein post-processing the medical device comprises immersing the medical device in an aqueous solution.
16. The method of claim 15 , wherein immersing the medical device in the aqueous solution comprises immersing the medical device in the aqueous solution for 5 minutes or less.
17. The method of claim 15 , wherein immersing the medical device in the aqueous solution comprises immersing the medical device in the aqueous solution for 1 minute or less.
18. The method of claim 2 , wherein post-processing the medical device comprises immersing the medical device in a solution comprising an organic solvent.
19. The method of claim 18 , wherein the solution further comprises water.
20. The method of claim 2 , wherein sterilizing the post-processed medical device comprises exposing the medical device to a relative humidity.
21. The method of claim 20 , wherein sterilizing comprises a pre-conditioning stage, a sterilization stage, and an aeration stage.