Transdermal delivery system for anti-emetic medication

• US 20050260252A1
• Filed: 04/27/2005
• Published: 11/24/2005
• Est. Priority Date: 10/31/2002
• Status: Active Grant

• Current Assignee: Syneron Medical Limited (Syneron Incorporated)
• Original Assignee: TransPharma Medical Ltd. (Syneron Incorporated)
• Inventors: Levin, Galit, Daniel, Dorit
• Granted Patent: US 7,415,306 B2
• Time in Patent Office: Days
• US Class Current: 424/448
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61K 9/7053 obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
• CPC Class Codes: A61K 9/7061 Polyacrylates
• CPC Class Codes: A61N 1/0476 Array electrodes (including any electrode arrangement with more than one electrode for at least one of the polarities)
• CPC Class Codes: A61N 1/0496 characterised by using specific chemical compositions, e.g. hydrogel compositions, adhesives
• CPC Class Codes: A61N 1/325 for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention provides a transdermal delivery system for hydrophilic anti-emetic agents and methods of using thereof. The system includes an anti-emetic hydrophilic adhesive composition of a hydrophilic polymer and hydrophilic anti-emetic agent, a patch containing at least one hydrophilic layer of the composition, and an apparatus that generates hydrophilic micro-channels in skin of a subject using the patch or composition. The system preferably avoids the use of penetration enhancers and is particularly useful for transdermal delivery of hydrophilic anti-emetic agents.

Claims

1. An anti-emetic hydrophilic adhesive composition comprising a hydrophilic polymer and a hydrophilic anti-emetic agent, devoid of penetration enhancers.

2. The composition according to claim 1, wherein the hydrophilic polymer is selected from the group consisting of cellulose, hydroxy cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polysaccharides, chitin, chitosan, diacylated chitin, gum acacia, agarose, carrageenan, gelatin, gum tragacanth, alginate, karaya gum, veegum, pectin, hyaluronic acid, pluronic acid, maltodextrin, polyvinylpyrrolidone, polyglycolic acid, polyoxyethylene, polyoxypropylene, colloidal silicon dioxide, polyvinyl alcohol, polyacrylamide, polyacrylic acid, polyacrylates, methacrylate polymers, and fumed silica.

3. The composition according to claim 1, wherein the anti-emetic agent is selected from the group consisting of dopamine antagonists, acetylcholine receptor antagonists, 5-hydroxytryptamine receptor antagonists, and pharmaceutically acceptable salts, and hydrates thereof.

4. The composition according to claim 3, wherein the 5-hydroxytryptamine receptor antagonist is selected from the group of hydrophilic derivatives of granisetron, ondansetron, lerisetron, dolasetron, tropisetron, itasetron, ramosetron.

5. The composition according to claim 1, wherein said composition further comprises at least one component selected from a plasticizer, a cross-linker, a buffering agent, a stabilizer, and an anti-oxidant.

7. A patch comprising at least one hydrophilic layer comprising the composition according to claim 1.

8. The patch according to claim 7, further comprising at least one layer selected from a backing layer, an adhesive, and a release liner.

9. A system for transdermal delivery of a hydrophilic anti-emetic agent from a pharmaceutical composition comprising:

an apparatus for facilitating transdermal delivery of a hydrophilic anti-emetic agent through skin of a subject, said apparatus capable of generating at least one micro-channel in an area on the skin of the subject; and

the patch according to claim 7.

6. (canceled)

10. A system for transdermal delivery of a hydrophilic anti-emetic agent from a pharmaceutical composition comprising:

an apparatus for facilitating transdermal delivery of a hydrophilic anti-emetic agent through skin of a subject, said apparatus capable of generating at least one micro-channel in an area on the skin of the subject; and

a patch comprising at least one hydrophilic layer comprising a therapeutically effective amount of the hydrophilic anti-emetic agent in a pharmaceutical composition.

11. The system according to claim 10, wherein the patch further comprising at least one layer selected from a backing layer, an adhesive, and a release liner.

12. The system according to claim 10, wherein the hydrophilic layer comprises at least one hydrophilic polymer.

13. The system according to claim 12, wherein the hydrophilic polymer is selected from the group consisting of cellulose, hydroxy cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polysaccharides, chitin, chitosan, diacylated chitin, gum acacia, agarose, carrageenan, gelatin, gum tragacanth, alginate, karaya gum, veegum, pectin, hyaluronic acid, pluronic acid, maltodextrin, polyvinylpyrrolidone, polyglycolic acid, polyoxyethylene, polyoxypropylene, colloidal silicon dioxide, polyvinyl alcohol, polyacrylamide, polyacrylic acid, polyacrylates, methacrylate polymers, and fumed silica.

14. The system according to claim 10, comprising an apparatus for facilitating transdermal delivery of a hydrophilic anti-emetic agent through skin of a subject, said apparatus comprising:

a. an electrode cartridge comprising at least one electrode; and

b. a main unit comprising a control unit which is adapted to apply electrical energy to the electrode when the electrode is in vicinity of the skin, typically generating current flow or one or more sparks, enabling ablation of stratum corneum in an area beneath the electrode, thereby generating at least one micro-channel.

15. The system according to claim 14, wherein the electrode cartridge is removable.

16. The system according to claim 14, wherein the electrode cartridge comprises a plurality of electrodes capable of generating a plurality of micro-channels of uniform shape and dimensions.

17. The system according to claim 14, wherein the electrical energy is of radio frequency.

18. A method for transdermal administration of a hydrophilic anti-emetic agent comprising:

(a) generating at least one micro-channel in an area of skin of a subject; and

(b) affixing a patch comprising at least one hydrophilic layer comprising a therapeutically effective amount of an anti-emetic agent to the area of skin in which the micro-channels are present.

19. A method of transdermal administration of a hydrophilic anti-emetic agent comprising:

(a) generating at least one micro-channel in an area of the skin of a subject;

(b) affixing a patch comprising at least one hydrophilic layer comprising a therapeutically effective amount of an anti-emetic agent to the area of skin in which the micro-channels are present, and (c) achieving a therapeutically effective serum concentration of the anti-emetic agent of at least 1 ng/ml.

20. The method according to claim 19 wherein the therapeutically effective serum concentration of the anti-emetic agent of at least 1 ng/ml is maintained for at least 24 to 48 hours.