Microneedle device having a peptide therapeutic agent and an amino acid and methods of making and using the same
View Patent ↗A medical device including an array of microneedles and a coating disposed on or within the microneedles and a method of making such a device are disclosed. The coating includes a peptide therapeutic agent and an amino acid. A method of stabilizing a peptide therapeutic agent with an amino acid on an array of microneedles is also disclosed. In some cases, the peptide therapeutic agent and the amino acid either both have a net positive charge or both have a net negative charge. In some cases, the peptide therapeutic agent is histidine.
1. A medical device comprising:
an array of microneedles; and
a coating on or within at least a portion of the microneedles, wherein the coating comprises:
a peptide therapeutic agent; and
histidine,
wherein the molar ratio of the histidine to the peptide therapeutic agent is less than 2:1, wherein the histidine stabilizes the peptide therapeutic agent in the coating, and wherein the peptide therapeutic agent is a parathyroid hormone-related protein (PTHrP) analogue represented by formula [Glu 22,25 ,Leu 23,28,31 ,Aib 29 ,Lys 26,30 ]hPTHrP(1-34)NH 2 .
2. The medical device of claim 1 , wherein the molar ratio of the histidine to the peptide therapeutic agent is less than 1.5:1.
3. A method of making a medical device comprising an array of microneedles and a coating on or within at least a portion of the microneedles, wherein the coating comprises:
a peptide therapeutic agent; and
histidine,
wherein the molar ratio of the histidine to the peptide therapeutic agent is less than 2:1, the method comprising:
providing an aqueous composition comprising the peptide therapeutic agent and histidine, wherein the molar ratio of the histidine to the peptide therapeutic agent in the aqueous composition is less than 2:1;
contacting the microneedles with the aqueous composition; and
volatilizing a portion of the aqueous composition to provide a coating on at least a portion of the microneedles, wherein the coating comprises at least the peptide therapeutic agent and the histidine, and wherein the peptide therapeutic agent is a parathyroid hormone-related protein (PTHrP) analogue represented by formula [Glu 22,25 ,Leu 23,28,31 ,Aib 29 ,Lys 26,30 ]hPTHrP(1-34)NH 2 .
4. The method of claim 3 , wherein the aqueous composition has a pH in a range from 3 to 11.
5. The method of claim 3 , wherein the molar ratio of histidine to the peptide therapeutic agent is less than 1.5:1.
6. The method of claim 3 , wherein histidine is present in the coating in a range from 0.1 to 15 percent by weight, based on the total weight of the coating.
7. The method of claim 3 , wherein the aqueous composition further comprises a buffer, wherein the buffer comprises phosphate, acetate, citrate, or tris(hydroxymethyl)aminomethane.
8. The method of claim 3 , wherein the coating is present on the microneedles in an average amount of 0.01 to 2 micrograms per microneedle.
9. The method of claim 3 , wherein the aqueous composition is substantially free of sorbitol.
10. The medical device of claim 1 , wherein histidine is present in the coating in a range from 0.1 to 15 percent by weight, based on the total weight of the coating.
11. The medical device of claim 1 , wherein the coating is present on the microneedles in an average amount of 0.01 to 2 micrograms per microneedle.
12. The medical device of claim 1 , wherein the coating is substantially free of sorbitol.
13. A medical device comprising:
an array of microneedles; and
a coating on or within at least a portion of the microneedles, wherein the coating comprises:
a peptide therapeutic agent; and
histidine,
wherein the molar ratio of the histidine to the peptide therapeutic agent is in a range from 0.25:1 to 55:1, and wherein the peptide therapeutic agent is a parathyroid hormone-related protein (PTHrP) analogue represented by formula [Glu 22,25 ,Leu 23,28,31 ,Aib 29 ,Lys 26,30 ]hPTHrP(1-34)NH 2 .
14. The medical device of claim 13 , wherein the histidine stabilizes the peptide therapeutic agent in the coating.
15. The medical device of claim 13 , wherein histidine is present in the coating in a range from 0.1 to 15 percent by weight, based on the total weight of the coating.
16. The medical device of claim 13 , wherein the coating is present on the microneedles in an average amount of 0.01 to 2 micrograms per microneedle.
17. The medical device of claim 13 , wherein the coating is substantially free of sorbitol.
18. The medical device of claim 13 , wherein the array of microneedles comprises a dissolvable matrix material.
19. The medical device of claim 13 , wherein at least some of the microneedles are hollow.