Transdermal Pharmaceutical Spray Formulations Comprising a Vp/Va Copolymer and a Non-Aquous Vehicle

• US 20070219171A1
• Filed: 10/21/2004
• Published: 09/20/2007
• Est. Priority Date: 10/23/2003
• Status: Abandoned Application

• Current Assignee: Cipla (EU) Limited
• Original Assignee: Waterleaf Limited
• Inventors: Lulla, Amar, Malhotra, Geena
• Application Number:
  US10/576,908
• Publication Number:
  US 20070219171A1
• Time in Patent Office: Days
• US Class Current: 514/177
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• 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 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

Transdermal spray formulations containing a pharmaceutically active agent and methods for administering the same are provided. The formulations comprise the pharmaceutically active agent, a VP/VA copolymer and a non-aqueous vehicle. The formulations further comprise an anti-nucleating agent to prevent recrystallization of the pharmaceutically active agent and a penetration enhancer to increase the rate of drug delivery through the skin. Upon application to the skin, the present formulations dry to provide a film at the site of treatment.

Claims

1. A transdermal spray formulation comprising:

a) a pharmaceutically active agent;

b) 0.1% to 2.0% by weight VP/VA copolymer;

c) at least 60% by weight of a non-aqueous solvent; and

d) optionally a penetration enhancer, which, if present, is present in an amount of 0.01% to 5.0% by weight of the composition.

2. A transdermal spray formulation according to claim 1, wherein the pharmaceutically active agent is provided in a therapeutically effective amount.

3. A transdermal spray formulation according to claim 1, further comprising an anti-nucleating agent.

4. A transdermal spray formulation according to claim 3, wherein the anti-nucleating agent is a polyvinylpyrrolidone polymer or copolymer.

5. A transdermal spray formulation according to claim 3, wherein the anti-nucleating agent comprises from about 1% to about 10% by weight of the formulation.

6. A transdermal spray formulation according to claim 1, wherein the penetration enhancer is a monohydric alcohol such as ethanol, isopropyl, butyl or benzyl alcohol;

a dihydric alcohol such as ethylene glycol, diethylene glycol propylene glycol, dipropylene glycol or trimethylene glycol;

a polyhydric alcohol such as glycerin, sorbitol or polyethylene glycol;

a polyethylene glycol ether of an aliphatic alcohol, such as cetyl, lauryl, oleyl or stearyl, including polyoxyethylene (4) lauryl ether, polyoxyethylene (2) oleyl ether, plyoxyethylene (10) oleyl ether or polyoxyethylene alkyl ether;

vegetable, animal or fish fats or oil such as olive and castor oils, squalene or lanolin;

a fatty acid ester such as propyl oleate, decyl oleate, isopropyl palmitate, glycol palmitate, glycol laurate, dodecyl myristate, isopropyl myristate or glycol stearate;

a fatty acid alcohol such as oleyl alcohol and derivatives thereof, a fatty acid amide such as oleamide and derivatives thereof;

urea and urea derivatives such as allantoin;

a polar solvent such as dimethyllaurylamide, dodecylpyrrolidone, isosorbitol, or salicylic acid;

an amino acid;

a higher molecular weight aliphatic surfactant such as lauryl sulfate salts or esters of sorbitol and sorbitol anhydride;

polysorbates 20. 21. 40, 60, 61. 65, 80, 81, or 85;

oleic and linoleic acids, ascorbic acid, panthenol, butylated hydroxytoluene, tocopherol, tocopherol acetate, tocopheryl linoleate, menthol, dimethylisosorbide, glycerylmono-oleate or myristyl lactate.

7. A transdermal spray formulation according to claim 1, wherein the penetration enhancer is selected from the group consisting of menthol, dimethylisosorbide, glycerylmono-oleate and myristyl lactate.

8. A transdermal spray formulation according to claim 1, wherein the non-aqueous solvent is volatile and evaporates at mammalian skin temperature.

9. A transdermal spray formulation according to claim 1, wherein the non-aqueous vehicle is one or more of ethanol, acetone and methylal.

10. A transdermal spray formulation according to claim 1, wherein the pharmaceutically active agent is one or more of the following classes;

anti-inflammatory drugs, analgesics, anti-arthritic drugs, antispasmodics, antidepressants, anti-psychotics, tranquillisers, anti-anxiety drugs, narcotic antagonists, antiparkinsonian agents, cholinergic agonists, chemotherapeutic drugs, immunosuppressive agents, antiviral agents, antibiotic agents, appetite suppressants, anti-emetics, anti-cholinergics, antihistaminics, anti-migraine agents, coronary, cerebral or peripheral vasodilators, hormonal agents, contraceptives, anti-thrombotic agents, diuretics, antihypertensive agents, cardiovascular drugs and opioids.

11. A transdermal spray formulation according to claim 1, wherein the pharmaceutically active agent is one or more of estradiol, testosterone, oxybutynin, buprenorphine and fentanyl.

12. A transdermal spray formulation according to claim 1, wherein the pharmaceutically active agent is estradiol.

13. A transdermal spray formulation according to claim 12, wherein the estradiol is present in an amount from about 1% to about 5% by weight of the formulation.

14. A transdermal spray formulation according to claim 1, wherein the pharmaceutically active agent is testosterone.

15. A transdermal spray formulation according to claim 14, wherein the testosterone is present in an amount up to about 16.66% by weight of the formulation.

16. A transdermal spray formulation according to claim 1 for forming a patch on the skin of a subject, wherein the non-aqueous solvent comprises ethanol, methylal or acetone or mixtures thereof;

and wherein the optional penetration enhancer, when present, is different to the non-aqueous solvent.

17. A transdermal spray formulation according to claim 16, wherein the non-aqueous solvent comprises ethanol.

18. A method of administering a pharmaceutically active agent, comprising spraying a transdermal formulation according to claim 1 onto the skin of a subject in need thereof.

19. A method according to claim 18, wherein the non-aqueous solvent volatizes upon contact with the skin, forming a film comprising the VP/VA copolymer and the pharmaceutically active agent.

20. A method of forming a pharmaceutically active film comprising spraying a transdermal formulation according to claim 1 on the skin of a subject in need thereof.