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

Patent metadata

Field	Value
Publication number	US-11058684-B2
Application number	US-201816180731-A
Country	US
Kind code	B2
Filing date	Nov 5, 2018
Priority date	Jul 28, 2014
Publication date	Jul 13, 2021
Grant date	Jul 13, 2021

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. An ophthalmic formulation comprising an aqueous suspension containing brimonidine or its pharmaceutically acceptable salt at a concentration of from about 0.05 to about 0.5% weight by volume, and a cation exchange resin, wherein the suspension is suitable for once-a-day topical instillation.

2. The ophthalmic formulation according to claim 1 , wherein the pharmaceutically acceptable salt of brimonidine is a tartrate salt.

3. The ophthalmic formulation according to claim 1 , wherein the suspension comprises a pH adjusting agent and the pH of the aqueous suspension is in the range of from about 7.0 to about 8.0.

4. The ophthalmic formulation according to claim 1 , wherein the cation exchange resin is polystyrene divinyl benzene sulphonate.

5. The ophthalmic formulation according to claim 2 , wherein the weight ratio between brimonidine and cation exchange resin is in the range of from about 0.3:1 to about 1:0.3.

6. The ophthalmic formulation according to claim 1 , wherein the suspension comprises one or more suspending agents selected from carbopol, polyvinylpyrrolidone or hydroxypropyl methylcellulose.

7. The ophthalmic formulation according to claim 1 , wherein a particle size distribution of the cation exchange resin particles complexed with brimonidine is such that the D 50 value is from about 50 nanometers to about 350 nanometers.

8. The ophthalmic formulation according to claim 1 , wherein the cation exchange resin is polystyrene divinyl benzene sulphonate and the weight ratio between brimonidine and cation exchange resin is in the range of from about 0.3:1 to about 1:0.3.

9. An ophthalmic formulation of brimonidine, comprising brimonidine or a pharmaceutically acceptable salt thereof at a concentration of about 0.35% weight by volume, a cation exchange resin, and a suspending agent, wherein the ophthalmic formulation is an aqueous suspension and is suitable for once-a-day topical instillation.

10. The ophthalmic formulation according to claim 9 , wherein the suspending agent is selected from carbopol, polyvinylpyrrolidone, hydroxypropyl methylcellulose or mixtures thereof.

11. An ophthalmic formulation, comprising (a) reversible clusters of drug loaded ion-exchange resin particles, said clusters have a D 50 value of at least 2 micrometers and (b) a suspending agent, wherein the ophthalmic formulation is an aqueous suspension and the drug is brimonidine or its pharmaceutically acceptable salt at a concentration of from about 0.05% to about 0.5% weight by volume.

12. The ophthalmic formulation of claim 11 , wherein the ion-exchange resin is a cation-exchange resin.

13. The ophthalmic formulation of claim 12 , wherein the cation-exchange resin is polystyrene divinyl benzene sulphonate and the weight ratio between brimonidine and the cation exchange resin is from about 0.3:1 to about 1:0.3.

14. The ophthalmic formulation of claim 11 , wherein the suspending agent comprises one or more suspending agents selected from carbopol, polyvinylpyrrolidone or hydroxypropyl methylcellulose.

15. The ophthalmic formulation of claim 11 , wherein the formulation comprises a pH adjusting agent and the pH of the aqueous suspension is in the range of from about 7.0 to about 8.0.

16. The ophthalmic formulation of claim 11 , which is suitable for once-a-day topical instillation.

17. The ophthalmic formulation of claim 11 , wherein the drug is the tartrate salt of brimonidine.

18. The ophthalmic formulation of claim 11 , wherein the brimonidine or a pharmaceutically acceptable salt thereof is at a concentration of about 0.35% weight by volume.

19. The ophthalmic formulation of claim 11 , wherein the drug loaded ion-exchange resin particles deagglomerate into individual drug loaded ion-exchange resin particles having a D 50 value from about 50 nanometers to about 350 nanometers.

Assignees

• Sun Pharma Advanced Res Co Ltd

Inventors

• Khopade Ajay Jaysingh
• Halder Arindam

Classifications

• A61K31/498 Primary

  Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine · CPC title

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title

• A61K45/06

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

• A61K9/0051

  Ocular inserts or implants · CPC title

• B01J39/20

  obtained by reactions only involving unsaturated carbon-to-carbon bonds · CPC title