Patches, formulations, and associated methods for transdermal delivery of alprazolam and other drugs
View Patent ↗The present invention is drawn to transdermal drug formulations, transdermal patches incorporating such formulations, as well as associated methods. The formulations can include about 0.3 wt % to about 5 wt % of a drug, such as alprazolam, about 4 wt % to about 30 wt % water, about 10 wt % to about 40 wt % glycerol, about 0.5 wt % to about 6 wt % oleyl alcohol. Other co-solvents and/or additives can be present to achieve a 100 wt % formulation.
1. A formulation for transdermal delivery of a drug, comprising
from about 0.3 wt % to about 5 wt % of alprazolam,
from about 4 wt % to about 30 wt % water,
from about 10 wt % to about 40 wt % glycerol, and
from about 0.5 wt % to about 6 wt % oleyl alcohol,
wherein the alprazolam in the formulation has a degradation rate of less than 5% per year at 25° C.
2. A formulation as in claim 1 , further comprising from about 20 wt % to about 85 wt % of additional solvent.
3. A formulation as in claim 1 , wherein alprazolam comprises about 0.5 wt % to about 3 wt % of the formulation.
4. A formulation as in claim 1 , wherein alprazolam comprises about 0.8 wt % to about 1.8 wt % of the formulation.
5. A formulation as in claim 1 , wherein alprazolam comprises about 1.0 wt % to about 1.5 wt % of the formulation.
6. A formulation as in claim 1 , wherein water comprises about 5 wt % to about 25 wt % of the formulation.
7. A formulation as in claim 1 , wherein water comprises about 6 wt % to about 15 wt % of the formulation.
8. A formulation as in claim 1 , wherein glycerol comprises about 15 wt % to 37 wt % about of the formulation.
9. A formulation as in claim 1 , wherein glycerol comprises about 20 wt % to about 35 wt % of the formulation.
10. A formulation as in claim 1 , wherein the oleyl alcohol comprises about 1 wt % to about 5 wt % of the formulation.
11. A formulation as in claim 1 , wherein the oleyl alcohol comprises about 2 wt % to about 4 wt % of the formulation.
12. A formulation as in claim 2 , wherein the additional solvent includes propylene glycol.
13. A formulation as in claim 1 , wherein the formulation has a pH of 7.0 to 10.
14. A formulation as in claim 1 , wherein the formulation includes a compound selected from the group consisting of BHT and EDTA.
15. A formulation as in claim 1 , wherein the formulation includes a skin irritation reduction agent selected from the group consisting of corticosteroids and anti-inflammatory agents.
16. A formulation as in claim 1 , wherein the formulation has a viscosity of about 20,000 to centipoise to about 200,000 centipoise.
17. A formulation as in claim 1 , incorporated in a transdermal patch.
18. A transdermal patch for transdermal delivery of alprazolam, comprising:
a transdermal drug formulation incorporated into a transdermal patch, said transdermal drug formulation comprising from about 0.3 wt % to about 5 wt % alprazolam, from about 4 wt % to about 30 wt % water, from about 10 wt % to about 40 wt % glycerol, from about 0.5 wt % to about 6 wt % oleyl alcohol, and optionally from about 20 wt % to about 85 wt % of additional solvent, wherein the alprazolam in the formulation has a degradation rate of less than 5% per year at 25° C.
19. A transdermal patch as in claim 18 , wherein the patch has a formulation-skin contact area of from 2 cm 2 to 100 cm 2 .
20. A transdermal patch as in claim 18 , wherein the patch has a formulation-skin contact area of from 5 cm 2 to 60 cm 2 .
21. A patch as in claim 20 , wherein each square centimeter of the formulation-skin contact area generates a mean AUC of at least 20 ng·hr/ml when administered to at least 10 human adults for a 72 hour period of time.
22. A transdermal patch as in claim 20 , wherein each square centimeter of the formulation-skin contact area generates a mean AUC of at least 34 ng·hr/ml when administered to at least 10 human adults for a 72 hour period of time.
23. A transdermal patch as in claim 20 , wherein each square centimeter of the formulation-skin contact area generates a mean AUC of at least 50 ng·hr/ml when administered to at least 10 human adults for a 72 hour period of time.
24. A transdermal patch as in claim 20 , wherein the total quantity of alprazolam in said patch per cm 2 of the transdermal drug formulation-skin contact area is less than 2 mg/cm 2 .
25. A transdermal patch as in claim 18 , wherein the patch includes a microporous non-rate-limiting membrane.
26. A transdermal patch as in claim 18 , wherein the patch is configured to deliver alprazolam therapeutically effective rates for a period of at least 48 hours.
27. A formulation for transdermal delivery of alprazolam, comprising:
alprazolam,
about 6 wt % to about 15 wt % water,
about 20 wt % to about 35 wt % glycerol,
about 40% to about 70% propylene glycol, and
about 2 wt % to about 4 wt % oleyl alcohol
wherein the alprazolam in the formulation has a degradation rate of less than 5% per year at 25° C.
28. A formulation as in claim 27 incorporated into a transdermal patch.
29. A formulation as in claim 27 , said formulation having a pH of 7-10.
30. A formulation as in claim 27 , wherein the alprazolam is present at from about 1.0 wt % to about 1.5 wt %.
31. A transdermal patch for transdermal delivery of alprazolam, comprising:
a transdermal drug formulation incorporated in a transdermal patch, wherein the transdermal drug formulation comprises about 1.0 wt % to about 1.5 wt % alprazolam, about 6 wt % to about 15 wt % water, about 20 wt % to about 35 wt % glycerol, about 40% to about 70% propylene glycol, from about 2 wt % to about 4 wt % oleyl alcohol, and has a pH of 7-10; wherein each square centimeter of the contact area between said formulation and the skin is capable of generating a mean AUC of at least 50 ng.hr/ml when administered to at least 10 human adults for a 72 hour period of time and wherein the alprazolam in the formulation has a degradation rate of less than 5% per year at 25° C.
32. A method of treating anxiety disorder or panic disorder in a subject, comprising:
applying a transdermal drug formulation to a skin surface of a subject, said transdermal formulation comprising from about 0.3 wt % to about 5 wt % alprazolam, from about 4 wt % to about 30 wt % water, from about 10 wt % to about 40 wt % glycerol, and from about 0.5 wt % to about 6 wt % oleyl alcohol and optionally about 20 wt % to about 85 wt % of additional solvent; and
maintaining said transdermal drug formulation in contact with said skin surface for a period of at least 48 hours.
33. A method as in claim 32 , wherein the applying step is by applying the transdermal drug formulation to the skin surface by way of a transdermal patch which includes the transdermal drug formulation.