Topical steroid composition and method

• US 8,962,028 B2
• Filed: 06/19/2013
• Issued: 02/24/2015
• Est. Priority Date: 10/18/2012
• Status: Active Grant

• Current Assignee: Therapeutics Incorporated
• Original Assignee: Mical Pharmaceuticals LLC - H Series A Series of Mical Pharmaceuticals LLC A Multi-Div
• Inventors: Johnson, Keith A., Popp, Karl F.
• Primary Examiner(s): Arnold, Ernst V
• Assistant Examiner(s): Chang, Kyung Sook
• Application Number:
  US13/921,833
• Publication Number:
  US 20140112991A1
• Time in Patent Office: 615 Days
• Field of Search: None
• US Class Current: 424/489
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 47/08 containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• 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 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/16 Emollients or protectives, e.g. against radiation
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin

Abstract

Storage stable, topical lotion compositions for treating corticosteroid-responsive dermatoses are provided by the present invention which include a halobetasol material comprising halobetasol or its pharmaceutically acceptable salts, esters, and solvates; and a pharmaceutically acceptable carrier which includes: (a) one or more fatty alcohols and/or one or more alkoxylated fatty alcohols, (b) one or more polyol humectants, and (c) diisopropyl adipate. Storage stable, topical lotion compositions for treating corticosteroid-responsive dermatoses are provided by the present invention which include 0.05% halobetasol propionate; and a pharmaceutically acceptable carrier which includes: (a) one or more fatty alcohols and/or one or more alkoxylated fatty alcohols, (b) one or more polyol humectants, and (c) diisopropyl adipate.

Claims

1. A storage stable, topical lotion composition for treating a skin disorder or condition, said composition comprising:

a halobetasol material comprising halobetasol or its pharmaceutically acceptable salts, esters, and solvates; and

a pharmaceutically acceptable carrier which includes;

(a) one or more fatty alcohols and/or one or more alkoxylated fatty alcohols, (b) one or more polyol humectants, and (c) diisopropyl adipate, wherein the amount of said halobetasol material after storage for six months at 40°

C. is >

98.5% of the total amount of halobetasol material present at the time of manufacture of the topical lotion, wherein the amount of degradation of said halobetasol material after storage for 26 months at 30°

C. is <

1% of the total amount of halobetasol material present at the time of manufacture of the topical lotion and wherein the amount of degradation of said halobetasol material after storage at 25°

C. for 30 months is <

3% of the total amount of halobetasol material present at the time of manufacture of the topical lotion, and

wherein the ratio of said fatty alcohols and alkoxylated fatty alcohols to said humectants, to said diisopropyl adipate is, on a weight basis, in the range of 30-60;

30-60;

5-15.

2. The topical lotion of claim 1, wherein the fatty alcohol is selected from the group consisting of lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, octyldodecanol, and mixtures of any two or more thereof.

3. The topical lotion of claim 1, wherein the alkoxylated fatty alcohol is an ethoxylated alcohol selected from the group consisting of lauryl alcohol ethoxylate, myristyl alcohol ethoxylate, cetyl alcohol ethoxylate, stearyl alcohol ethoxylate, octyldodecanol ethoxylate, and mixtures of any two or more thereof.

4. The topical lotion of claim 1, wherein the polyol humectant is selected from the group consisting of glycerin, propylene glycol, butylene glycol, dipropylene glycol, pentylene glycol, hexylene glycol, polyethylene glycol and mixtures of any two or more thereof.

5. The topical lotion of claim 1, wherein the amount of degradation of said halobetasol material after storage for six months at 40°

C. is <

1.5% of the total amount of said halobetasol material, wherein the amount of degradation of said halobetasol material after storage for 26 months at 30°

C. is <

1% of said halobetasol material and wherein the amount of degradation of said halobetasol material after storage at 25°

C. for 30 months is <

3% of said halobetasol material.

6. The topical lotion of claim 1, wherein said halobetasol material is halobetasol propionate.

7. The topical lotion of claim 1, further including one or more members selected from the group consisting of:

one or more additional therapeutic agents, coloring agents, preservatives, pH control agents, viscosity control agents, and fragrances.

8. The topical lotion of claim 1, wherein the ratio of said fatty alcohols and alkoxylated fatty alcohols to said humectants, to said diisopropyl adipate is, on a weight basis, in the range of 39-48:

39-50;

10-15.

9. The topical lotion of claim 1, wherein the weight ratio of said fatty alcohols and ethoxylated fatty alcohols to said polyol humectants to said diisopropyl adipate is in the range of 44-46:

40-43;

11-13.

10. The topical lotion of claim 1, wherein the weight ratio of said fatty alcohols and ethoxylated fatty alcohols to said polyol humectants to said diisopropyl adipate is 46:

42;

12.

11. The topical lotion of claim 1, wherein said topical lotion composition is an oil-in-water emulsion of droplets having a mean particle size in the range of 0.1-50 microns and a distribution of particle sizes in the range of 0.1-50 microns.

12. The topical lotion of claim 1, wherein said topical lotion composition is an oil-in-water emulsion of droplets having a mean particle size in the range of 1-10 microns and a distribution of particle sizes in the range of 0.15-15 microns.

13. The topical lotion of claim 1, wherein said topical lotion composition is an oil-in-water emulsion of droplets having a mean particle size in the range of 1.5-7 microns and a distribution of particle sizes in the range of 0.175-10 microns.

14. The storage stable, topical lotion composition of claim 1 comprising, on a weight basis:

0.02-0.10% of a halobetasol material;

1-5% of diisopropyl adipate;

5-15% octyl dodecanol;

0.50-2% of polyethylene glycol 1000 cetyl ether;

0.50-2% of a surfactant;

1-3% cetyl alcohol;

1-2% stearyl alcohol;

0.05-0.2% of a preservative;

5-15% propylene glycol;

1-5% glycerin;

a pH adjustment agent an amount sufficient to adjust the pH of the composition to a range of approximately 5-6.5; and

water q.s.

15. The storage stable, topical lotion composition of claim 14, further comprising a viscosity control agent in an amount of 0.1-0.5% w/w.

16. The storage stable, topical lotion composition of claim 1 comprising, on a weight basis:

0.05% of a halobetasol material;

3.5% of diisopropyl adipate;

10% octyl dodecanol;

1% of polyethylene glycol 1000 cetyl ether;

1% of a surfactant;

2% cetyl alcohol;

0.66% stearyl alcohol;

0.15% of a preservative;

10% propylene glycol;

2.5% glycerin;

a pH adjustment agent in an amount sufficient to adjust the pH of the composition to a range of approximately 5-6.5; and

water q.s.

17. The storage stable, topical lotion composition of claim 16 wherein the preservative is propyl paraben, butyl paraben or a combination of propyl paraben and butyl paraben.

18. The storage stable, topical lotion composition of claim 16, further comprising a viscosity control agent in an amount of 0.25% w/w.

19. A method for treating corticosteroid-responsive dermatoses comprising:

topically administering to a patient in need thereof, the topical lotion composition of claim 1.

20. The method of claim 19, wherein said topical lotion composition is packaged in a container suitable for storage and delivery of said composition.

21. The method of claim 20, wherein said container is comprised of a ferrous alloy, aluminum, glass, plastic, or combinations thereof.

22. The method of claim 20, wherein said container further includes one or more protective coatings.

23. The method of claim 20, wherein said container includes at least two separate compartments wherein said topical lotion composition of claim 1 is disposed in one of said compartments.

24. The method of claim 19, wherein the patient is further instructed to prepare the area to be treated by cleansing with a suitable surfactant-containing composition.

25. The method of claim 19, wherein said method is as effective to reduce transepidermal water loss as a cream formulation, Ultravate Cream®

compared to a shaved skin control.

26. The method of claim 19, wherein said method is effective to produce an improvement in skin surface hydration levels as measured with a skin conductance or capacitance measuring apparatus.

27. The method of claim 26, wherein said improvement is observed at 2 hours post treatment.

28. The method of claim 26, wherein said improvement is observed at 4 hours post treatment.

29. A method for the preparation of the topical lotion composition of claim 1, said method comprising the steps of:

preparing an aqueous phase that includes a first portion of the components of said topical lotion composition;

maintaining said aqueous phase at a temperature in the range of 45-70°

C.;

preparing an oil phase that includes a second portion of the components of said topical lotion composition;

adding said oil phase to said aqueous phase while stirring at a temperature of about 45-70°

C. so as to obtain an emulsion;

cooling said emulsion to a temperature of about 25-35°

C.; and

adjusting the pH of said emulsion to a pH in the range of 5.0-6.5.