Stable ophthalmic formulations

1. A stable ophthalmic pharmaceutical composition for the treatment of glaucoma, ocular hypertension, or a combination thereof, the stable ophthalmic pharmaceutical composition comprising: (a) a therapeutically-effective amount of dorzolamide, or a pharmaceutically acceptable salt thereof, (b) a therapeutically-effective amount of latanoprost, and (c) a cyclodextrin, wherein the composition has a pH between about 6.0 and about 6.2, and wherein the composition is stable with respect to degradation of the dorzolamide and latanoprost for at least 4 months.

2. The stable ophthalmic pharmaceutical composition according to claim 1 , further comprising a mucoadhesive, a preservative, a pH-adjusting agent, a tonicity-adjusting agent, a buffering agent, an antioxidant, or a combination thereof.

3. The stable ophthalmic pharmaceutical composition according to claim 2 , further comprising a therapeutically effective amount of an additional anti-glaucoma agent.

4. The stable ophthalmic pharmaceutical composition according to claim 3 , wherein the additional anti-glaucoma agent is a beta blocker.

5. The stable ophthalmic pharmaceutical composition according to claim 4 , wherein the beta blocker is timolol.

6. The stable ophthalmic pharmaceutical composition according to claim 1 , wherein the pharmaceutically acceptable salt of dorzolamide is dorzolamide hydrochloride.

7. The stable ophthalmic pharmaceutical composition according to claim 1 , wherein the cyclodextrin is hydroxypropyl-β-cyclodextrin.

8. The stable ophthalmic pharmaceutical composition according to claim 2 , wherein the mucoadhesive is hyaluronic acid or a pharmaceutically acceptable salt thereof, polyvinyl alcohol, polyvinyl-pyrrolidone, hydroxypropyl-methylcellulose, carboxymethyl-cellulose, hydroxyethyl cellulose, a poloxamer, alginic acid, chitosan, xanthan gum, carrageenan, acrylic acid, acrylic acid derivatives, or a combination thereof.

9. The stable ophthalmic pharmaceutical composition according to claim 2 , wherein the preservative is benzalkonium chloride, chlorobutanol, phenylmercuric acetate, phenylmercuric nitrate, polyhexinide, cetrimide, cetylpyridinium chloride, EDTA, or a combination thereof.

10. The stable ophthalmic pharmaceutical composition of claim 2 , wherein the pH-adjusting agent is hydrochloric acid, boric acid, acetic acid, sodium hydroxide, potassium hydroxide, or a combination thereof.

11. The stable ophthalmic pharmaceutical composition of claim 2 , wherein the tonicity-adjusting agent is sodium chloride, potassium chloride, mannitol, glycerol, sorbitol, xylitol, or a combination thereof.

12. The stable ophthalmic pharmaceutical composition of claim 2 , wherein the buffering agent is an acetate buffer, a citrate buffer, a phosphate buffer, a borate buffer, or a combination thereof.

13. The stable ophthalmic pharmaceutical composition of claim 2 , wherein the antioxidant is sodium metabisulfite, sodium thiosulfate, acetyl cysteine, BHA, BHT, vitamin E, ascorbic acid, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, or a combination thereof.

14. The stable ophthalmic pharmaceutical composition according to claim 1 , wherein the composition comprises the following components in the following weight percentages:

dorzolamide hydrochloride

1-3%

latanoprost

0.003-0.01% 

HP-β-cyclodextrin

  2-10%.

15. A stable ophthalmic pharmaceutical composition comprising: (a) a therapeutically-effective amount of dorzolamide, or a pharmaceutically acceptable salt thereof, (b) a therapeutically-effective amount of lantanoprost, and (c) a cyclodextrin, wherein the composition has a pH between about 6.0 and about 6.2, and wherein the composition is stable with respect to degradation of the dorzolamide and latanoprost for at least 4 months.

16. The stable ophthalmic pharmaceutical composition according to claim 15 , wherein after 6 months of storage at 25° C. or at 40° C., the composition comprises at least 97% of the initial amount of dorzolamide, and at least 98% of the initial amount of latanoprost.

17. A method of treating glaucoma, ocular hypertension, or a combination thereof, comprising topically administering a stable ophthalmic pharmaceutical composition according to claim 1 to the eye of a patient in need thereof.