Method of increasing bioavailability and/or prolonging ophthalmic action of a drug

Patent metadata

Field	Value
Publication number	US-10172852-B2
Application number	US-201515329824-A
Country	US
Kind code	B2
Filing date	Jul 24, 2015
Priority date	Jul 28, 2014
Publication date	Jan 8, 2019
Grant date	Jan 8, 2019

Abstract

The present invention relates to a method of increasing the bioavailability and/or prolonging ophthalmic action of a drug, the method comprising instilling into the eye an aqueous suspension comprising reversible clusters of drug loaded nano-resin particles, said clusters having a D50 value of at least 2 micrometer and said drug loaded nano-resin particles have a particle size distribution characterized in that the D90 value is 70 nanometer to 900 nanometer. The present invention further relates to an aqueous suspension comprising reversible clusters of drug loaded nano-resin particles, said clusters have a D50 value of at least 2 micrometers and said drug loaded nano-resin particles have a particle size distribution characterized in that the D90 value is 70 nanometers to 900 nanometers.

First claim

The invention claimed is:

1. A method of increasing the bioavailability and/or prolonging ophthalmic action of a drug, the method comprising instilling into the eye an aqueous suspension comprising (a) reversible clusters of drug loaded ion-exchange resin particles, said clusters have a D 50 value of at least 2 micrometer and said drug loaded ion-exchange resin particles have a particle size distribution characterized in that the D 90 value is 70 nanometers to 900 nanometers and (b) a suspending agent.

2. The method as claimed in claim 1 , wherein the D 90 value is 200 nanometer to 700 nanometer.

3. The method as claimed in claim 1 , wherein the drug is selected from brimonidine, doxycycline, bromfenac, olopatadine, emedastine, dorzolamide, ciprofloxacin, moxifloxacin, besifloxacin, gentamicin, neomycin, polymyxin B, ketotifen, phenylephrine, pyrilamine, dipivefrin, oxymetazoline, levocabastine, azelastine, epinastine, bepotastine, dipivefrin, naphazoline, apraclonidine, levobunolol, betaxolol, levobetaxolol, timolol, carteolol, dextromethorphan, cyclopentolate, proparacaine, pilocarpine, diclofenac, sulfacetamide, flurbiprofen, ketorolac or their pharmaceutically acceptable salts or mixtures thereof.

4. The method as claimed in claim 3 , wherein the drug is brimonidine or its pharmaceutically acceptable salt and is present at a concentration of 0.05% to 0.5% weight by volume.

5. The method as claimed in claim 4 , wherein brimonidine or its pharmaceutically acceptable salt is brimonidine tartarate and it is present at a concentration of 0.35% weight by volume.

6. The method as claimed in claim 1 , wherein the drug loaded ion-exchange resin particles have a particle size distribution characterized in that the D50 value is 50 nanometer to 350 nanometer.

7. The method as claimed in claim 1 , wherein the ion-exchange resin is selected from a cation exchange nano-resin or an anion exchange nano-resin.

8. The method as claimed in claim 7 , wherein the cation exchange nano-resin is polystyrene divinyl benzene sulfonate.

9. The method as claimed in claim 1 , wherein the suspending agent is selected from an anionic polymer, a non-ionic polymer or mixtures thereof.

10. The method as claimed in claim 5 , wherein the aqueous suspension is instilled into the eye once-a-day for the treatment of glaucoma.

11. An aqueous suspension comprising (a) reversible clusters of drug loaded ion-exchange resin particles, said clusters have a D 50 value of at least 2 micrometers and said drug loaded ion-exchange resin particles have a particle size distribution characterized in that the D 90 value is 70 nanometers to 900 nanometers, and (b) a suspending agent.

12. The aqueous suspension as claimed in claim 11 , wherein the D 90 value is 200 nanometers to 700 nanometers.

13. The aqueous suspension as claimed in claim 11 , wherein the drug is selected from brimonidine, doxycycline, bromfenac, olopatadine, emedastine, dorzolamide, ciprofloxacin, moxifloxacin, besifloxacin, gentamicin, neomycin, polymyxin B, ketotifen, phenylephrine, pyrilamine, dipivefrin, oxymetazoline, levocabastine, azelastine, epinastine, bepotastine, dipivefrin, naphazoline, apraclonidine, levobunolol, betaxolol, levobetaxolol, timolol, carteolol, dextromethorphan, cyclopentolate, proparacaine, pilocarpine, diclofenac, sulfacetamide, flurbiprofen, ketorolac or their pharmaceutically acceptable salts or mixtures thereof.

14. The aqueous suspension as claimed in claim 13 , wherein the drug is brimonidine or its pharmaceutically acceptable salt and is present at a concentration of 0.05% to 0.5% weight by volume.

15. The aqueous suspension as claimed in claim 14 , wherein brimonidine or its pharmaceutically acceptable salt is brimonidine tartarate and it is present at a concentration of 0.35% weight by volume.

16. The aqueous suspension as claimed in claim 11 , wherein the drug loaded ion-exchange resin particles have a particle size distribution characterized in that the D50 value is 50 nanometers to 350 nanometers.

17. The aqueous suspension as claimed in claim 11 , wherein the ion-exchange resin is selected from a cation exchange nano-resin or an anion exchange nano-resin.

18. The aqueous suspension as claimed in claim 17 , wherein the cation exchange nano-resin is polystyrene divinyl benzene sulfonate.

19. The aqueous suspension as claimed in claim 11 , wherein the suspending agent is selected from an anionic polymer, a non-ionic polymer or mixtures thereof.

Assignees

• Sun Pharma Advanced Res Co Ltd
• Sun Pharma Advanced Res Co Ltd

Inventors

• Khopade Ajay Jaysingh
• Halder Arindam

Classifications

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61K9/1635

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K9/5176

  Compounds of unknown constitution, e.g. material from plants or animals (oils, fats, waxes, shellac A61K9/5123) · CPC title