Topical composition comprising a film-forming polymer for delivering an active ingredient to skin

Patent metadata

Field	Value
Publication number	US-9345774-B2
Application number	US-201314412978-A
Country	US
Kind code	B2
Filing date	Jul 5, 2013
Priority date	Jul 6, 2012
Publication date	May 24, 2016
Grant date	May 24, 2016

Abstract

A sprayable film-forming pharmaceutical composition for dermal application comprises at least one therapeutically active ingredient dissolved in a pharmaceutically acceptable propellant selected from the group consisting of dimethyl ether, diethyl ether and methylethylether, and a mixture of dimethyl ether, diethylether and methylethyl ether, and a second propellant selected from C 3-5 alkanes, hydrofluoroalkanes, hydrochloroalkanes, fluoroalkanes and chlorofluoroalkanes, the propellant being present in an amount of 50-99.5% w/w of the composition, the composition further comprising a film-forming polymer, a plasticizer and an oily release-enhancing agent.

First claim

The invention claimed is:

1. A substantially anhydrous sprayable film-forming pharmaceutical composition for dermal application, the composition comprising:
at least one therapeutically active ingredient dissolved in a pharmaceutically acceptable propellant mixture of dimethyl ether and a second propellant selected from the group consisting of C 3-5 alkanes and hydrofluoroalkanes, wherein the propellant is present in an amount of 50-99.5% w/w of the composition,
a film-forming polymer in an amount of 0.1-50% w/w,
a plasticizer in an amount of 0.1-10% w/w, and
medium chain triglycerides as an oily release-enhancing agent in an amount of 0.1-15% w/w,
wherein the composition is essentially free from a low-molecular volatile solvent.

2. A composition according to claim 1 , wherein the film-forming polymer is selected from the group consisting of cellulose derivatives, acrylic polymers, acrylic copolymers, methacrylate polymers, methacrylate copolymers, polyurethanes, polyvinylalcohol or a derivative thereof such as polyvinylacetate, silicone polymers and silicone copolymers, or copolymers thereof.

3. A composition according to claim 2 , wherein the cellulose derivative is selected from the group consisting of ethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose.

4. A composition according to claim 2 , wherein the acrylic polymer is selected from the group consisting of methyl methacrylate and butyl methacrylate copolymer, ethyl acrylate and methyl methacrylate copolymer, acrylate and ammonium methacrylate copolymer type A and type B, and acrylates/octylacrylamide copolymer.

5. A composition according to claim 1 , wherein the plasticizer is selected from the group consisting of triethyl citrate, tributyl citrate, acetyl triethyl citrate, triacetin, dibutyl sebacate and polyethylene glycol 100-1000.

6. A composition according to claim 1 , wherein the second propellant C 3-5 alkane is selected from the group consisting of n-propane, isopropane, n-butane or isobutane.

7. A composition according to claim 6 , wherein the C 3-5 alkane is n-butane and/or isobutane.

8. A composition according to claim 7 , wherein the ratio of n-butane and/or isobutane to dimethyl ether is in the range of 6:1-0:1 v/v.

9. A composition according to claim 1 further comprising an anti-nucleating agent.

10. A composition according to claim 9 , wherein the anti-nucleating agent is selected from the group consisting of polyvinyl alcohol, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, polyvinylpyrrolidone and carboxymethyl cellulose.

11. A composition according to claim 1 , wherein the therapeutically active ingredient is selected from the group consisting of vitamin D derivatives or analogues, corticosteroids, phosphodiesterase 4 inhibitors, ingenol derivatives, retinoids, JAK inhibitors, NK-1 receptor antagonists, calcineurin inhibitors, keratolytic agents,antibiotics, non-steroidal antiinflammatory agents and local anesthetics.

12. A composition according to claim 11 comprising calcipotriol or calcipotriol monohydrate as the vitamin D analogue and betamethasone dipropionate or valerate as the corticosteroid.

13. A pressurized container adapted to dispensing a topical composition on an affected skin area, the container including a container body comprising a composition according to claim 1 and a valve assembly including an actuator for releasing the composition as a spray.

14. A container according to claim 13 , wherein the valve assembly contains at least one aperture with a diameter of 0.05-1 mm.

15. A container according to claim 13 , wherein the actuator is provided with an orifice with a diameter of 0.3-1.5 mm.

16. A method of treating dermatological diseases or conditions, wherein the method comprises applying a therapeutically effective amount of the composition of claim 1 on to the skin of a patient in need of treatment.

17. The method of claim 16 , wherein the dermatological disease or condition is selected from the group consisting of psoriasis, pustulosis palmoplantaris, ichtyosis, atopic dermatitis, contact dermatitis, eczema, actinic keratosis, pruritus, rosacea and acne.

18. A composition according to claim 7 , wherein the ratio of n-butane and/or isobutane to dimethyl ether is in the range of 4:1-1:1.

19. A composition according to claim 7 , wherein the ratio of n-butane and/or isobutane to dimethyl ether is in the range of 4:2-1:1.

20. A composition according to claim 1 , wherein the therapeutically active ingredient is selected from the group consisting of vitamin D derivatives or analogues, corticosteroids, phosphodiesterase 4 inhibitors, ingenol derivatives, adapalene, JAK inhibitors, NK-1 receptor antagonists, tacrolimus, pimecrolimus, salicylic acid, lactic acid, fusidic acid, clindamycin, non-steroidal antiinflammatory agents and lidocain.

Assignees

• Leo Pharma As

Inventors

• Petersson Karsten
• Frederiksen Kit
• Omkvist Diana
• Jansson Jörgen

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P17/06

  Antipsoriatics · CPC title