Transdermal delivery of non-steroidal anti-inflammatory drugs

• US 7,387,789 B2
• Filed: 09/08/2006
• Issued: 06/17/2008
• Est. Priority Date: 02/19/1996
• Status: Expired due to Fees

• Current Assignee: Acrux DDS Pty Ltd (Acrux Limited)
• Original Assignee: Acrux DDS Pty Ltd (Acrux Limited)
• Inventors: Bakalova, Margarita Vladislavova, Finnin, Barrie Charles, Reed, Barry Leonard, Morgan, Timothy Matthias, Klose, Kathryn Traci-Jane
• Primary Examiner(s): Richter; Johann
• Assistant Examiner(s): George; Konata M.
• Application Number:
  US11/517,575
• Publication Number:
  US 20070077288A1
• Time in Patent Office: 648 Days
• Field of Search: 424/449, 514/506
• US Class Current: 424/449
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 8/046 Aerosols; Foams
• CPC Class Codes: A61K 8/37 Esters of carboxylic acids
• CPC Class Codes: A61K 8/445 aromatic, i.e. the carboxylic acid directly linked to the aromatic ring
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/12 Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61M 35/003 Portable hand-held applicators having means for dispensing or spreading integral media hand-held massage devices with liquid delivery A61H7/003
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 15/16 Masculine contraceptives
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 : Anxiolytics
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 5/24 : of the sex hormones
• CPC Class Codes: A61P 5/26 : Androgens
• CPC Class Codes: A61P 5/30 : Oestrogens
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: A61Q 17/04 : Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides a transdermal drug delivery system which comprises: a therapeutically effective amount of a non-steroidal anti-inflammatory drug; at least one dermal penetration enhancer, which is a safe skin-tolerant ester sunscreen ester; and at least one volatile liquid. The invention also provides a method for administering at least one systemic or locally acting non-steroidal anti-inflammatory drug to an animal which comprises applying an effective amount of the non-steroidal anti-inflammatory drug in the form of the drug delivery system of the present invention.

Claims

1. A transdermal drug delivery system comprising:

(a) a therapeutically effective amount of a non-steroidal anti-inflammatory drug;

(b) at least one dermal penetration enhancer, which is a safe skin-tolerant ester sunscreen of formula (I);

2. The transdermal drug delivery system according to claim 1, wherein the dermal penetration enhancer is octyl salicylate.

3. The transdermal drug delivery system according to claim 1, wherein the volatile liquid selected from the group consisting of ethanol, isopropanol, and a mixture thereof.

4. The transdermal drug delivery system according to claim 1, comprising on a weight basis:

(a) from about 1 to about 15% of said non-steroidal anti-inflammatory drug;

(b) from about 1 to about 10% of said at least one dermal penetration enhancer; and

(c) from about 75 to about 98% of said volatile liquid.

5. The transdermal drug delivery system according to claim 1, wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of acemetacin, amtolmetin, azapropazone, benorilate, benoxaprofen, benzydamine hydrochloride, bromfenal, bufexamac, butibufen, carprofen, celecoxib, choline salicylate, dipyone, droxicam, etodolac, etofenamate, etoricoxib, felbinac, fentiazac, floctafenine, indoprofen, isoxicam, lomoxicam, loxoprofen, licofelone, fepradinol, magnesium salicylate, meclofenamic acid, meloxicam, morniflumate, niflumic acid, nimesulide, oxaprozen, piketoprofen, priazolac, pirprofen, propyphenazone, proquazone, rofecoxib, salalate, sodium salicylate, sodium thiosalicylate, suprofen, tenidap, tiaprofenic acid, trolamine salicylate, and zomepirac.

6. The transdermal drug delivery system according to claim 1, wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of aclofenac, aloxiprin, aproxen, aspirin, diflunisal, fenoprofen, indomethacin, mefenamic acid, piroxicam, phenylbutazone, salicylamide, salicylic acid, sulindac, desoxysulindac, tenoxicam, tramadol, ketoralac, clonixin, fenbufen, benzydamine hydrochloride, meclofenamic acid, flufenamic acid and tolmetin.

7. The transdermal drug delivery system according to claim 1, wherein the non-steroidal anti-inflammatory drug is piroxicam.

8. The transdermal drug delivery system according to claim 1, wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of ibuprofen, naproxen, flurbiprofen, diclofenac, and ketoprofen.

9. The transdermal drug delivery system according to claim 8, comprising on a weight basis:

(a) from about 1 to about 15% ibuprofen;

(b) from about 1 to about 10% octyl salicylate; and

(c) from about 75 to about 98% Alcohol USP (95% ethanol).

10. The transdermal drug delivery system according to claim 8, comprising on a weight basis:

(a) from about 1 to about 5% ibuprofen;

(b) from about 1 to about 5% octyl salicylate; and

(c) from about 45 to about 90% of a volataile liquid selected from the group consisting of ethanol, isopropanol, and a mixture thereof;

(d) from about 5 to about 45% water; and

(e) from about 0.5 to about 5% of a thickening agent.

11. A method for administering at least one systemic or locally acting non-steroidal anti-inflammatory drug to an animal which comprises applying an effective amount of the non-steroidal anti-inflammatory drug in the form of the drug delivery system according to claim 1.

12. The method according to claim 11, wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of acemetacin, amtolmetin, azapropazone, benorilate, benoxaprofen, benzydamine hydrochlorie, bromfenal, bufexamac, butibufen, carprofen, celecoxib, choline salicylate, dipyone, droxicam, etodolac, etofenamate, etoricoxib, felbinac, fentiazac, floctafenine, indoprofen, isoxicam, lomoxicam, loxoprofen, licofelone, fepradinol, magnesium salicylate, meclofenamic acid, meloxicam, morniflumate, niflumic acid, nimesulide, oxaprozen, piketoprofen, priazolac, pirprofen, propyphenazone, proquazone, rofecoxib, salalate, sodium salicylate, sodium thiosalicylate, suprofen, tenidap, tiaprofenic acid, trolamine salicylate, and zomepirac.

13. The method according to claim 12, wherein the non-steroidal anti-inflammatory drug is piroxicam.

14. The method according to claim 11, wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of aclofenac, aloxiprin, aproxen, aspirin, diflunisal, fenoprofen, indomethacin, mefenamic acid, piroxicam, phenylbutazone, salicylamide, salicylic acid, sulindac, desoxysulindac, tenoxicam, tramadol, ketoralac, clonixin, fenbufen, benzydamine hydrochloride, meclofenamic acid, flufenamic acid and tolmetin.

15. The method according to claim 11, wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of ibuprofen, naproxen, flurbiprofen, diclofenac, and ketoprofen.

16. The method according to claim 11, wherein the drug delivery system is applied to the skin of the animal covering a delivery surface area between about 10 and 2000 cm².

17. The method according to claim 11, wherein the drug delivery system is applied to the skin of the animal covering a delivery surface area between about 10 and 400 cm².

18. The method according to claim 11, wherein the drug delivery system is applied to the skin of the animal covering a delivery surface area between about 10 and 200 cm².

19. The method according to claim 11, wherein the drug delivery system is applied using a fixed or variable metered dose applicator.