Transdermal Methods And Systems For The Delivery Of Rizatriptan

1 . A method for treating a subject for a rizatriptan responsive state, comprising transdermally administering to the subject an effective amount of rizatriptan or a salt thereof in less than 45 minutes using an integrated iontophoretic patch, wherein the rizatriptan or salt thereof is formulated in a flowable hydrogel and wherein said patch uses a current density selected such that said current does not substantially irritate said subject's skin.

2 . The method according to claim 1 , wherein an effective amount of rizatriptan or a salt thereof is administered to the subject in less than 30 minutes.

3 . The method according to any one of the preceding claims, wherein the patch provides rizatriptan at an iontophoretic flux rate of about 22.9 mcg/cm 2 /min or greater across the subject's skin.

4 . The method according to any one of the preceding claims, wherein the patch provides rizatriptan at an iontophoretic flux rate of about 28.5 mcg/cm 2 /min or greater across the subject's skin.

5 . The method according to any of the preceding claims, wherein said patch uses an average current density of 0.20 mA/cm 2 or less for a significant portion of delivery time of the rizatriptan or salt thereof.

6 . The method according to any of the preceding claims, wherein said patch uses an average current density of 0.15 mA/cm 2 or less for a significant portion of delivery time of the rizatriptan or salt thereof.

7 . The method according to any of the preceding claims, wherein said patch uses an average current density of 0.10 mA/cm 2 or less for a significant portion of delivery time of the rizatriptan or salt thereof.

8 . The method according to any of the preceding claims, wherein said patch uses an average current density of 0.05 mA/cm 2 or less for a significant portion of delivery time of the rizatriptan or salt thereof.

9 . The method according to any of the preceding claims, wherein the patch provides an uninterrupted two-stage patterned delivery sequence wherein current densities average between about 0.05 and about 0.40 mA/cm 2 during a significant portion of a first stage followed by a second stage delivery wherein current densities average between about 0.01 and about 0.40 mA/cm 2 during a significant portion of the second stage, to provide a waveform delivery pattern in which a therapeutically effective dosage level is reached in a subject in less than about one hour and a maintenance level is continued for one or more hours.

10 . The method according to any one of the preceding claims, wherein usage of the patch to deliver a steady state concentration of said rizatriptan results in a mean skin erythema score of 1.00 or less immediately after patch removal.

11 . The method according to any one of the preceding claims, wherein usage of the patch to deliver a steady state concentration of said rizatriptan results in a mean skin erythema score of 0.50 or less immediately after patch removal.

12 . The method according to any one of the preceding claims, wherein usage of the patch to deliver a steady state concentration of said rizatriptan results in a mean skin erythema score of zero immediately after patch removal.

13 . The method according to any one of the preceding claims, wherein said hydrogel comprises a flux enhancer.

14 . The method according to claim 13 , wherein the flux enhancer is a flux enhancer which is uncharged at neutral pH.

15 . The method according to claim 13 , wherein the flux enhancer is at least one enhancer selected from lauric acid, polyoxyethylene (4) lauryl ether and mixtures thereof.

16 . The method according to claim 13 , wherein said hydrogel comprises at least about 3.4% polyoxyethylene (4) lauryl ether.

17 . The method according to claim 1 , wherein the effective amount is a concentration of about 20 ng/mL or less in the subject's blood.

18 . The method according to claim 1 , wherein the patch is able to maintain an effective steady state concentration of the rizatriptan or salt thereof in the subject's blood for at least about an hour.

19 . An integrated iontophoretic transdermal patch for the delivery of rizatriptan or a salt thereof to a subject in need thereof, comprising

a controller to deliver at least a portion of said rizatriptan or salt thereof to the subject by driving an electrotransport current through an animal body surface using a controllable power supply;

an electrode which does not form an insoluble salt of the rizatriptan or salt thereof; and

a composition comprising rizatriptan or a salt thereof formulated in a flowable hydrogel;

wherein the patch delivers an effective amount of rizatriptan or a salt thereof to the subject in less than 45 minutes.

20 . The patch according to claim 19 , wherein the patch provides rizatriptan at an iontophoretic flux rate of about 22.9 mcg/cm 2 /min or greater across the subject's skin.

21 . The patch according to any one of claims 19 - 20 , wherein the patch provides rizatriptan at an iontophoretic flux rate of about 28.5 mcg/cm 2 /min or greater across the subject's skin.

22 . The patch according to any one of claims 19 - 21 , wherein the controller provides an uninterrupted two-stage patterned delivery sequence wherein current densities average between about 0.05 and about 0.20 mA/cm 2 during a significant portion of a first stage followed by a second stage delivery wherein current densities average between about 0.01 and about 0.20 mA/cm 2 during a significant portion of the second stage, to provide a waveform delivery pattern in which a therapeutically effective dosage level is reached in a subject in less than about one hour and a maintenance level is continued for one or more hours.

23 . The patch according to any one of claims 19 - 22 , wherein usage of the patch to deliver a steady state concentration of the rizatriptan or salt thereof results in a mean skin erythema score of 1.00 or less immediately after patch removal.

24 . The patch according to any one of claims 19 - 23 , wherein said hydrogel contains a flux enhancer.

25 . The patch according to claim 24 , wherein the flux enhancer is a flux enhancer which is uncharged at neutral pH.

26 . The patch according to claim 24 , wherein the flux enhancer is at least one enhancer selected from lauric acid, polyoxyethylene (4) lauryl ether, sorbitan laurate and mixtures thereof.

27 . The patch according to claim 24 , comprising at least 4% rizatriptan and at least 3.4% polyoxyethylene (4) lauryl ether.