Topical pharmaceutical composition of acitretin

Patent metadata

Field	Value
Publication number	US-10123987-B2
Application number	US-201415033676-A
Country	US
Kind code	B2
Filing date	Oct 30, 2014
Priority date	Oct 31, 2013
Publication date	Nov 13, 2018
Grant date	Nov 13, 2018

Abstract

The present invention relates to a topical pharmaceutical composition comprising acitretin and a process for its preparation. It also relates to a method of treating skin disorders by administering said topical pharmaceutical composition.

First claim

We claim:

1. A stable topical pharmaceutical composition of acitretin comprising a therapeutically effective amount of acitretin from about 0.05% w/w to about 0.2% w/w based on total weight of the composition, a gelling agent, a solvent, and a co-solvent.

2. A stable topical pharmaceutical composition comprising from about 0.05% w/w to about 0.2% w/w of acitretin based on total weight of the composition, wherein more than about 15% of the acitretin is present in a solubilized form.

3. The stable topical pharmaceutical composition of claim 2 comprising about 0.05% w/w of acitretin based on total weight of the composition, wherein about 100% of the acitretin is present in the solubilized form.

4. The stable topical pharmaceutical composition of claim 2 comprising about 0.1% w/w of acitretin based on total weight of the composition, wherein about 70% of the acitretin is present in the solubilized form.

5. The stable topical pharmaceutical composition of claim 2 comprising about 0.2% w/w of acitretin based on total weight of the composition, wherein about 35% of the acitretin is present in the solubilized form.

6. The stable topical pharmaceutical composition of claim 2 , wherein the composition is a gel.

7. The stable topical pharmaceutical composition of claim 2 , wherein the composition comprises a gelling agent, a solvent, and a co-solvent.

8. The stable topical pharmaceutical composition of claim 1 or 7 , wherein the percentage of the gelling agent ranges from about 0.05% w/w to about 10% w/w based on total weight of the composition.

9. The stable topical pharmaceutical composition of claim 1 or 7 , wherein the gelling agent is selected from the group comprising carboxyvinyl polymers, natural gums, cellulose derivatives, acrylates, alginic acid-propylene glycol ester, polyoxyethylene-polyoxypropylene copolymers, polyvinyl pyrrolidone, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, silicon dioxide, and mixtures thereof.

10. The stable topical pharmaceutical composition of claim 9 , wherein the gelling agent is a carboxyvinyl polymer.

11. The stable topical pharmaceutical composition of claim 1 or 7 , wherein the solvent is selected from the group comprising water, white soft paraffin, light liquid paraffin, heavy liquid paraffin, mineral oil, hydrocarbon oil, ester oil, triglyceride oil, oil of plant origin, oil of animal origin, unsaturated or polyunsaturated oil, essential oil, silicone oil, and mixtures thereof.

12. The stable topical pharmaceutical composition of claim 11 , wherein the solvent is water.

13. The stable topical pharmaceutical composition of claim 1 or 7 , wherein the co-solvent is selected from the group comprising ethers, glycols, dimethyl isosorbide, fatty acid esters, fatty acids, polyoxyethylene sorbitan esters, and mixtures thereof.

14. The stable topical pharmaceutical composition of claim 13 , wherein the co-solvent is diethylene glycol monoethyl ether.

15. The stable topical pharmaceutical composition of claim 13 , wherein the co-solvent is dimethyl isosorbide.

16. The stable topical pharmaceutical composition of claim 13 , wherein the co-solvent is polysorbate 80.

17. The stable topical pharmaceutical composition of claim 13 , wherein the co-solvent is a combination of diethylene glycol monoethyl ether, dimethyl isosorbide; and polysorbate 80.

18. The stable topical pharmaceutical composition of claim 17 , wherein diethylene glycol monoethyl ether is present in a range of about 20% to about 30% w/w based on total weight of the composition.

19. The stable topical pharmaceutical composition of claim 17 , wherein dimethyl isosorbide is present in a range of about 1% to about 10% w/w based on total weight of the composition.

20. The stable topical pharmaceutical composition of claim 17 , wherein polysorbate 80 is present in a range of about 0.1% to about 5% w/w based on total weight of the composition.

21. The stable topical pharmaceutical composition of claim 1 or 7 , wherein the composition further comprises one or more pharmaceutically acceptable excipients selected from the group comprising percutaneous absorption enhancers, antioxidants, preservatives, chelating agents, surfactants, pH-adjusting agents, humectants, fragrances, and mixtures thereof.

22. The stable topical pharmaceutical composition of claim 1 or 7 , wherein the composition has a pH from about 4 to about 7.

23. A stable topical pharmaceutical composition comprising at least about 0.05% w/w of acitretin based on total weight of the composition, wherein the composition has a mean in-vitro release rate of more than about 10.00 μg/cm 2 /h 1/2 as measured using a Franz diffusion cell with the conditions of receptor solution comprising isopropyl alcohol and water (60:40, v/v), hydrophilic polyethersulfone (PES) membrane with pore size of 0.2 μm, dosage 300±30 mg, temperature 32° C.±1.0° C.

24. A method of treating a skin disorder by administering the stable topical pharmaceutical composition of claim 1 or 2 .

25. The method of treatment of claim 24 , wherein the skin disorder is selected from the group comprising psoriasis, keratosis, eczema, rosacea, acne vulgaris, dermatitis, pruritus, seborrhea, skin cancers, inflammation, other skin disorders which are responsive to acitretin or etretinate, and combinations thereof.

26. The method of treatment of claim 25 , wherein the skin disorder is psoriasis.

Assignees

• Sun Pharmaceutical Ind Ltd

Inventors

• Venkateshwaran Rathinasabapathy
• Jain Vikas
• Dubey Vaibhav
• Madan Sumit
• Arora Vinod Kumar
• Rao Rajesh

Classifications

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K31/202 Primary

  having three or more double bonds, e.g. linolenic (eicosanoids, e.g. leukotrienes A61K31/557) · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• A61K9/0014

  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 title

• A61K9/06

  Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} · CPC title