Ophthalmic formulations and uses thereof

1. A topical ophthalmic formulation comprising:

(a) physiologic levels of electrolytes mimicking serum levels;

(b) an antimicrobial compound;

(c) an anti-inflammatory or steroidal compound, and

(d) 150 ppm to 250 ppm benzalkonium chloride as a preservative,

the formulation excluding serum.

2. The formulation of claim 1 wherein (a), (b), (c), and (d) are in a single topical ophthalmic formulation.

3. The formulation of claim 1 wherein the antimicrobial compound is an aminoglycoside, fluoroquinolone, tetralide, and/or cephalosporin or their ophthalmically-acceptable derivatives.

4. The formulation of claim 1 wherein the antimicrobial compound is tobramycin, gentamicin, ciproflaxacin, norfloxacin, ofloxacin, and/or sparfloxacin; or their ophthalmically-acceptable derivatives.

5. The formulation of claim 1 wherein the antimicrobial compound is tobramycin or its ophthalmically-acceptable derivatives.

6. The formulation of claim 1 wherein the anti-inflammatory compound is diclofenac, bromfenac, dexamethasone and/or prednisolone or their ophthalmically-acceptable derivatives.

7. The formulation of claim 1 wherein the anti-inflammatory compound is prednisolone or its ophthalmically-acceptable derivatives.

8. The formulation of claim 1 wherein the steroidal compound is prednisolone, dexamethasone, fluormetholone, beta-methasone, and/or corticosterone or their ophthalmically-acceptable derivatives.

9. The formulation of claim 1 wherein the steroidal compound is prednisolone or its ophthalmically-acceptable derivatives.

10. The formulation of claim 1 which comprises potassium in a concentration from about 136.85 to about 207.23 mg/L.

11. The formulation of claim 1 which comprises the following ranges of electrolytes:

potassium in a concentration from about 136.85 to about 207.23 mg/L;

chloride in a concentration from about 3368.7 to about 3829.68 mg/L;

calcium in a concentration from about 85 to about 103 mg/L;

magnesium in a concentration from about 14.592 to about 24.32 mg/L; and

phosphate in a concentration from about 85 to about 150 mg/L.

12. The formulation of claim 1 which comprises the following ranges of electrolytes:

sodium in a concentration from about 3105 to about 3358 mg/L;

potassium in a concentration from about 136.85 to about 207.23 mg/L;

chloride in a concentration from about 3368.7 to about 3829.68 mg/L;

calcium in a concentration from about 85 to about 103 mg/L;

magnesium in a concentration from about 14.592 to about 24.32 mg/L;

phosphate in a concentration from about 85 to about 150 mg/L; and

bicarbonate in a concentration from about 1281 to about 2013 mg/L.

13. The formulation of claim 1 further comprising an additional ophthalmically-acceptable excipient.

14. The formulation of claim 13 wherein the excipient is a buffer, osmotic agent, demulcent, surfactant, emollient, and/or tonicity agent.

15. The formulation of claim 14 wherein the osmolality of the formulation is from about 200 to about 500 mOsm/Kg.

16. The formulation of claim 14 wherein the osmolality of the formulation is from about 250 to about 400 mOsm/Kg.

17. The formulation of claim 1 wherein the formulation is an aqueous, non-aqueous, gel, or ointment formulation.

18. The formulation of claim 1 containing 175 ppm to 225 ppm benzalkonium chloride as a preservative.

19. The formulation of claim 1 containing 200 ppm benzalkonium chloride as a preservative.

20. A composition for use in a topical ophthalmic formulation comprising:

Component

Amount/mL

%

Prednisolone Acetate USP

 0.01 g

1.040

Tobramycin USP

0.003 g

0.303

Hydroxypropyl Methylcellulose

0.003 g

0.300

USP

Polysorbate 80 NF

0.0005 g 

0.0500

Potassium Chloride USP

0.000275 g   

0.0275

Calcium Chloride, Dihydrate

0.000315 g   

0.0315

USP

Magnesium Chloride,

0.000125 g   

0.0125

Hexahydrate USP

Sodium Phosphate Dibasic,

0.00015 g  

0.015

Anhydrous USP

Benzalkonium Chloride NF,

0.000405

0.02025

50% Solution

(0.0002025 g of

(as 100%

100% BAK

BAK)

Sodium Chloride USP

0.00505 g  

0.505

Sodium Borate Decahydrate

0.0045 g 

0.450

USP

Sodium Sulfate Decahydrate

0.0038 g 

0.380

USP

Sulfuric Acid

As required

As required

for pH 6.85

for pH 6.85

Water For Injection USP

q.s. to 1 mLz

q.s. to 100%

the formulation excluding serum, the electrolytes in the formulation mimicking a physiologic serum amount or concentration.

21. The formulation of claim 20 wherein the osmolality of the formulation is from about 200 to about 500 mOsm/kg.

22. The formulation of claim 20 wherein the osmolality of the formulation is from about 250 to about 400 mOsm/kg.

23. An ophthalmic kit comprising the composition of claim 1 and a means to apply the composition to the eye.

24. An ophthalmic kit comprising the formulation of claim 20 and a means to apply the formulation to the eye.

25. The kit of claim 24 wherein the application means is an eye dropper, an eye cup, an eye spray or gel ointment tube.

26. The kit of claim 25 further comprising a single dose or a multi dose of the formulation in a single container.

27. A method of treating an ocular disease, injury or disorder comprising administering the formulation of claim 1 to a patient in need of such treatment.

28. The method of claim 27 wherein the ocular disease, injury or disorder is caused by surgery, physical damage to the eye, glaucoma, diabetic retinopathy, and/or macular degeneration.

29. The method of claim 28 wherein the ocular disease, injury or disorder is one which results in vascular leakage in the eye or by inflammation in the eye.

30. The method of claim 29 wherein the inflammation in the eye is caused by surgical trauma, dry eye, an allergic, viral, or bacterial infection, injury from a chemical, radiation or thermal burn, or penetration of a foreign body.

31. A method of treating an eye wherein its normal condition has been disrupted or changed comprising administering to the eye the composition of claim 1 .

32. A method of treating an eye wherein its normal condition has been disrupted or changed comprising administering to the eye the formulation of claim 20 .