ELECTROPHORETIC TRANSDERMAL DELIVERY SYSTEM

• US 20100189793A1
• Filed: 12/23/2009
• Published: 07/29/2010
• Est. Priority Date: 06/25/2007
• Status: Abandoned Application

• Current Assignee: Acino AG, Friedrich-Alexander-Universitat Erlangen-Nurnberg
• Original Assignee: Acino AG, Friedrich-Alexander-Universitat Erlangen-Nurnberg
• Inventors: NICKEL, Ulrich, ZOGLMEIER, Christine, MEYER, Elisabeth, SCHRÕDER, Britta
• Application Number:
  US12/646,780
• Publication Number:
  US 20100189793A1
• Time in Patent Office: Days
• US Class Current: 424/484
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61N 1/0436 Material of the electrode
• CPC Class Codes: A61N 1/044 Shape of the electrode
• CPC Class Codes: A61N 1/0444 Membrane
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

A transdermal delivery system (TDS) for administering at least one active agent through the skin. The system has a first electrode, a second electrode, and a matrix located between the first and second electrodes. The TDS contains at least one active agent which is either alkaline or acidic. The system is configured such that when applying a voltage to the electrodes, the pH of the matrix, in the case of an alkaline active agent, does not exceed the pH of the active agent and, in case of an acidic active agent, does not fall below the pH of the active agent.

Claims

1. A transdermal delivery system comprising:

a matrix containing at least one alkaline active agent;

a first electrode; and

a second electrode adapted for being penetrated by said at least one active agent;

whereby said matrix is located between said first electrode and said second electrode, said matrix has a pH which is lower than the pH of said at least one active agent, and whereby the system is configured such that a voltage applied to said first and second electrodes does not result in the pH of said matrix exceeding the pH of said at least one active agent, and wherein at least 75% of said alkaline active agent is provided in protonated form.

2. The transdenual delivery system according to claim 1, wherein at least 90% of said alkaline active agent is provided in protonated form.

3. The transdermal delivery system according to claim 1, wherein at least 99% of said alkaline active agent is provided in protonated form.

4. The transdermal delivery system according to claim 1, wherein said at least one alkaline active agent is selected from the group consisting of analgesics, μ

-opioid-receptor-antagonists, anaesthetics, parasympathomimetics, parasympatholytics, antiemetics, emetics, sympathomimetics, hormones, anti-migraine agents, antiallergics, anticonvulsants, anti-dementia drugs, antidepressants, beta receptor blocker, analeptics, and mixtures thereof.

5. The transdermal delivery system according to claim 4, wherein said at least one alkaline active agent is selected from the group consisting of fentanyl, buprenorphine, physostigmine, rivastigmine, scopolamine, granisetron, zolmitriptan, sumatriptan, salbutamol, and mixtures thereof.

6. The transdermal delivery system according to claim 1, wherein said matrix contains one or more additives selected from the group consisting of penetration enhancing or permeation enhancing compounds, or both, preservatives, antioxidants, humectants, electrolytes, thickening agents, emulsifiers, tackifiers, plasticizers, acidifying agents, alkalifying agents, buffers, fillers, and mixtures thereof.

7. The transdermal delivery system according to claim 1, wherein at least said first electrode is used as an anode and is a silver anode, and wherein said matrix contains chloride (Cl⁻

).

8. The transdermal delivery system according to claim 1, and further comprising a contact adhesive layer configured for contacting the skin upon application of the system.

9. The transdermal delivery system according to claim 8, wherein said contact adhesive layer also contains said at least one alkaline active agent.

10. The transdermal delivery system according to claim 1, and further comprising a backing foil impermeable to said active agent and being selectively permeable to gas.

11. The transdermal delivery system according to claim 1, and further comprising a voltage supply comprising a voltage source and a control device, spacers means, support element means and, selectively, pressure-sensitive contact adhesive layer means and removable release liner means.

15. A method for administering an active agent through the skin, wherein a transdermal delivery system according to claim 1 is attached to the skin of a human or animal body for a predetermined delivery time period, during which time a voltage is applied one or more times between the first and second electrode such that in case of an alkaline active agent the pH of the matrix does not exceed the pH of the at least one active agent, and such that in case of an acidic active agent the pH of the matrix does not fall below the pH of the at least one active agent.

17. The use of a transdermal delivery system according to claim 1 for administering at least one active agent through the skin.

18. The use of a transdermal delivery system according to claim 17 for administering at least one active agent through the skin.

12. A transdermal delivery system comprising:

a matrix containing at least one alkaline active agent being selected from the group consisting of analgesics, μ

-opioid-receptor-antagonists, anaesthetics, parasympathomimetics, parasympatholytics, antiemetics, emetics, sympathomimetics, hormones, anti-migraine agents, antiallergics, anticonvulsants, anti-dementia drugs, antidepressants, beta receptor blocker, analeptics, and mixtures thereof;

a first electrode;

a second electrode adapted for being penetrated by said at least one active agent; and

a backing foil being impermeable to said active agent;

whereby said matrix is located between said first electrode and said second electrode and has a pH which is lower than the pH of said at least one active agent, and whereby the system is configured such that a voltage applied to said first and second electrodes does not result in the pH of said matrix exceeding the pH of said at least one active agent, and wherein at least 75% of said alkaline active agent is provided in protonated form.

16. A method for administering an active agent through the skin, wherein a transdermal delivery system according to claim 12 is attached to the skin of a human or animal body for a predetermined delivery time period, during which time a voltage is applied one or more times between the first and second electrode such that in case of an alkaline active agent the pH of the matrix does not exceed the pH of the at least one active agent, and such that in case of an acidic active agent the pH of the matrix does not fall below the pH of the at least one active agent.

13. A transdermal delivery system (100) comprising:

a matrix (3) containing at least one alkaline active agent (4) being selected from the group consisting of analgesics, μ

-opioid-receptor-antagonists, anaesthetics, parasympathomimetics, parasympatholytics, antiemetics, emetics, sympathomimetics, hormones, anti-migraine agents, antiallergics, anticonvulsants, anti-dementia drugs, antidepressants, beta receptor blocker, analeptics, and mixtures thereof;

a first electrode;

a second electrode adapted for being penetrated by said at least one active agent;

a backing foil being impermeable for said active agent; and

a voltage supply comprising a voltage source and a control device;

whereby said matrix is located between said first electrode and said second electrode and has a pH which is lower than the pH of said at least one active agent, and whereby the system is configured such that a voltage applied to said first and second electrodes does not result in the pH of said matrix exceeding the pH of said at least one active agent, and wherein at least 75% of said alkaline active agent is provided in protonated form.

14. A transdermal delivery system comprising:

a matrix containing at least one acidic active agent;

a first electrode; and

a second electrode adapted for being penetrated by said at least one active agent;

whereby said matrix is located between said first electrode and said second electrode and has a pH which is higher than the pH of said at least one active agent, and whereby the system is configured such that a voltage applied to said first and second electrodes does not result in the pH of said matrix falling below the pH of said at least one active agent.