Suspension of loteprednol etabonate for ear, eye, or nose treatment

• US 5,540,930 A
• Filed: 10/25/1993
• Issued: 07/30/1996
• Est. Priority Date: 10/25/1993
• Status: Expired due to Term

• Current Assignee: Bausch & Lomb Incorporated (Bausch Health Cos., Inc.)
• Original Assignee: Pharmos Corporation
• Inventors: Friedman, Doron I., Guy, Yaacov J.
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US08/142,743
• Time in Patent Office: 1,009 Days
• Field of Search: 514/772.3, 514/772.2, 514/772.5, 514/778, 514/914, 424/489, 424/427, 424/428, 424/437
• US Class Current: 424/427
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 31/79 Polymers of vinyl pyrrolidone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The invention provides novel compositions of matter containing water-insoluble steroid drugs suitable for therapeutic use. The invention provides stable aqueous suspensions of water-insoluble steroid drugs of particle sizes of ≦15 μm which remain in such a state so as to allow for immediate suspension, when desired, even after extended periods of settling.

Claims

1. A composition for ophthalmic or otolaryngological anti-inflammatory use comprising:

(A) a corticosteroid having a particle size of 0.1 to 30 microns in diameter in an amount of about 0.2 to 2% by weight;

(B) a nonionic polymer in an aqueous medium;

(C) a nonionic surface active agent in an amount sufficient to retain the corticosteroid in suspension; and

(D) a nonionic tonicity agent in an amount sufficient to achieve isotonicity, wherein the molar ratio of (A);

(B);

(C) is between about 1;

20;

1 and about 1;

0.01;

0.5.

2. The composition of claim 1 wherein the corticosteroid is selected from the group consisting of soft steroids having anti-inflammatory activity.

3. The composition of claim 1 wherein the corticosteroid is loteprednol etabonate and is present in an amount of about 0.5 to 1% by weight.

4. The composition of claim 3 wherein said corticosteroid has a particle size less than about fifteen microns.

5. The composition of claim 1 further including a preservative for preventing microbial formation in said composition and in an amount of about 0.01 to 0.025% by weight.

6. The composition of claim 5 wherein said preservative is benzalkonium chloride.

7. The composition of claim 6 further comprising disodium edetate.

8. The composition of claim 1 wherein said nonionic polymer is selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, or dextran and is present in an amount of about 0.2 to 2% by weight and wherein the nonionic surfactant is present in an amount of about 0.05 to 1% by weight.

9. The composition of claim 1 wherein said nonionic polymer is polyvinylpyrrolidone and is present in an amount of about 0.4 to 1% by weight.

10. The composition of claim 1 wherein said nonionic surface active agent is tyloxapol and is present in an amount of about 0.1 to 0.6% by weight.

11. The composition of claim 1 further comprising an additional therapeutic drug in admixture with said corticosteroid, wherein said additional therapeutic drug is selected from the group consisting of betaxalol, athenolol, livobanolol, epinenephrin, dipivalyl, oxonolol, acetazilumide-base, methazalomide, tobramycin, gentamycin, piroxicam, indomethacin, naproxen, phenylbutazone, ibuprofen, and diclofenac-acid.

12. A composition for ophthalmic or otolaryngological anti-inflammatory use according to claim 1 in which the nonionic tonicity agent is glycerol in an amount 2 to 2.8%.

13. A composition for ophthalmic or otolaryngological anti-inflammatory use comprising a nonionic polymer in an aqueous medium, a nonionic tonicity agent in an amount effective to product isotonicity, and a nonionic surface active agent in an amount sufficient to retain the polymer and tonicity agent in the aqueous medium, and further comprising a corticosteroid having a particle size of 0.1 to 30 microns in diameter in an amount of about 0.2 to 2% by weight, wherein the molar ratio of corticosteroid to nonionic polymer to nonionic surface active agent is between about 1:

20;

1 and about 1;

0.01;

0.05.

14. The composition of claim 13 wherein said nonionic tonicity agent is a nonionic diol and is present in an amount of about 2 to 2.8% by weight.

15. The composition of claim 13 wherein the nonionic polymer is present in an amount of about 0.2 to 2% by weight;

the nonionic tonicity agent is present in an amount of about 2 to 2.8% by weight; and

the nonionic surface active agent is present in an amount of about 0.05 to 1% by weight.

16. The composition of claim 13 further comprising a preservative of benzalkonium chloride, disodium edetate, and mixtures thereof in an amount of about 0.01 to 0.025% by weight.

17. The composition of claim 13 wherein the nonionic polymer is polyvinyl pyrrolidone and is present in an amount of about 0.4 to 1% by weight, the nonionic tonicity agent is mannitol or a diol and is present in an amount of about 2 to 2.8% by weight, and the nonionic surface active agent is tyloxapol and is present in an amount of about 0.1 to 0.6% by weight.