Transdermal delivery system for water insoluble drugs

• US 20050287217A1
• Filed: 04/27/2005
• Published: 12/29/2005
• Est. Priority Date: 10/31/2002
• Status: Active Grant

• Current Assignee: Syneron Medical Limited (Syneron Incorporated)
• Original Assignee: TransPharma Medical Ltd. (Syneron Incorporated)
• Inventors: Stern, Meir, Levin, Galit, Daniel, Dorit
• Granted Patent: US 7,395,111 B2
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 9/703 characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61N 1/044 Shape of the electrode
• 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 1/40 Applying electric fields by inductive or capacitive coupling microwave apparatus A61N5/00; Applying radio-frequency signals

Abstract

The present invention provides a system for transdermal delivery of water insoluble drugs and methods using the same. The system includes a pharmaceutical composition of a water insoluble drug and a carrier molecule that enhances the solubility of the drug in aqueous solution, a medical patch containing the same and an apparatus that generates hydrophilic micro-channels in an area of skin of a subject using the composition or patch. The system preferably avoids the use of penetration enhancers and is particularly useful for transdermal delivery of steroids.

Claims

1. A pharmaceutical composition comprising a water insoluble drug and a carrier molecule that enhances the solubility of the drug in aqueous solution, devoid of penetration enhancers.

2. The pharmaceutical composition according to claim 1, wherein the water insoluble drug is selected from the group consisting of natural or synthetic anesthetics, analgesics, antagonists, antiadrenergic and antiarrhythmics, antibiotics, anticholinergic and cholinomimetic agents, anticonvulsant agents, antidepressants, anti-epileptics, antifungal and antiviral agents, anti-inflammatory agents, antimuscarinic and muscarinic agents, antineoplastic agents, antipsychotic agents, anxiolytics, hormones, hypnotics, immunosuppressive or immunoactive agents, neuroleptic agents, neuron blocking agents, antihypertensive agents, nutrients, sedatives, steroids, and derivatives thereof.

3. The pharmaceutical composition according to claim 1, wherein the carrier molecule is selected from the group consisting of α

, β

, and γ

cyclodextrins and derivatives thereof.

4. The pharmaceutical composition according to claim 1, wherein the water-insoluble drug is testosterone and the carrier molecule is sulfobutyl ether-P-cyclodextrin.

5. The pharmaceutical composition according to claim 1, further comprising at least one hydrophilic polymer.

6. The pharmaceutical composition according to claim 5, wherein the hydrophilic polymer is selected from the group consisting of polyglycolic acid and polylactic acid polymers, polyoxypropylene, polyoxyethylene, polyoxyethylene-polyoxypropylene copolymers, polyvinylalcohol, polyethylene glycol, polyvinylpyrrolidone, and polyurethanes.

7. The pharmaceutical composition according to claim 1, formulated in a form selected from the group consisting of a powder, a solution, a gel, or a hydrogel.

8. The pharmaceutical composition according to claim 1, further comprising at least one component selected from preservatives, anti-oxidants, anti-microbial agents, soluble polysaccharides, adhesives, and diluents.

9. A medical patch comprising a pharmaceutical composition according to claim 1.

10. A medical patch comprising a pharmaceutical composition comprising at least one water-insoluble drug and at least one carrier molecule that enhances the solubility of the drug in aqueous solution.

11. The patch according to claim 10, which further comprises a layer selected from a backing layer, adhesive, and a release liner.

12. A system for transdermal delivery of a water-insoluble drug comprising:

an apparatus for facilitating transdermal delivery of a drug 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 according to claim 10.

13. A system for transdermal delivery of a water-insoluble drug comprising:

an apparatus for facilitating transdermal delivery of a drug 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 a pharmaceutical composition comprising at least one water-insoluble drug and at least one carrier molecule that enhances the solubility of the drug in aqueous solution.

14. The system according to claim 13, comprising an apparatus for facilitating transdermal delivery of a drug 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 the stratum corneum in an area beneath the electrode, thereby generating at least one micro-channel.

15. The system according to claim 13, wherein the electrode cartridge comprises a plurality of electrodes capable of generating a plurality of micro-channels of uniform shape and dimensions.

16. The system according to claim 13, wherein the cartridge is removable.

17. The system according to claim 13, wherein the electrical energy applied to the electrode is of radio frequency.

18. A method for transdermal administration of a water-insoluble drug comprising:

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

(ii) affixing a patch comprising a pharmaceutical composition comprising at least one water-insoluble drug and at least one carrier molecule that enhances the drug solubility in an aqueous solution to the area of skin in which the micro-channels are present.

19. The method according to claim 18, wherein the water insoluble drug is selected from the group consisting of natural or synthetic anesthetics, analgesics, antagonists, antiadrenergic and antiarrhythmics, antibiotics, anticholinergic and cholinomimetic agents, anticonvulsant agents, antidepressants, anti-epileptics, antifungal and antiviral agents, anti-inflammatory agents, antimuscarinic and muscarinic agents, antineoplastic agents, antipsychotic agents, anxiolytics, hormones, hypnotics, immunosuppressive or immunoactive agents, neuroleptic agents, neuron blocking agents, antihypertensive agents, nutrients, sedatives, steroids, and derivatives thereof, and the carrier molecule is selected from the group consisting of α

, β

, and γ

cyclodextrins and derivatives thereof.

20. A method for transdermal administration of a water-insoluble drug comprising:

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

(ii) affixing a patch comprising a pharmaceutical composition comprising at least one water-insoluble drug and at least one carrier molecule that enhances the drug solubility in an aqueous solution to the area of skin in which the micro-channels are present; and

(iii) achieving a therapeutic blood concentration of the drug.

21. The method according to claim 20, wherein the water insoluble drug is selected from the group consisting of natural or synthetic anesthetics, analgesics, antagonists, antiadrenergic and antiarrhythmics, antibiotics, anticholinergic and cholinomimetic agents, anticonvulsant agents, antidepressants, anti-epileptics, antifungal and antiviral agents, anti-inflammatory agents, antimuscarinic and muscarinic agents, antineoplastic agents, antipsychotic agents, anxiolytics, hormones, hypnotics, immunosuppressive or immunoactive agents, neuroleptic agents, neuron blocking agents, antihypertensive agents, nutrients, sedatives, steroids, and derivatives thereof, and the carrier molecule is selected from the group consisting of α

, β

, and γ

cyclodextrins and derivatives thereof.