Stabilizing compositions for antibiotics and methods of use

• US 8,461,143 B2
• Filed: 11/18/2011
• Issued: 06/11/2013
• Est. Priority Date: 09/26/2006
• Status: Expired due to Fees

• Current Assignee: Taro Pharmaceutical North America Incorporated (Sun Pharmaceutical Industries Limited)
• Original Assignee: Taro Pharmaceutical North America Incorporated (Sun Pharmaceutical Industries Limited)
• Inventors: Gao, Shen, Moros, Daniel A., Asotra, Satish
• Primary Examiner(s): McCormick, Melenie
• Assistant Examiner(s): Betton, Timothy E
• Application Number:
  US13/299,829
• Publication Number:
  US 20120065182A1
• Time in Patent Office: 571 Days
• Field of Search: 514/192
• US Class Current: 514/192
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/424 condensed with heterocyclic ring systems, e.g. clavulanic acid
• CPC Class Codes: A61K 31/43 Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula , e.g. penicillins, penems
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention is directed to improved liquid antibiotic formulations. In some embodiments, the present invention is directed to a composition comprising an antibiotic in a liquid comprising triglycerides, wherein the composition has less than about 5% water (w/v).

Claims

1. A liquid pharmaceutical composition comprising a β

-lactam antibiotic;

one or more of dried silicon dioxide, dried colloidal silicon dioxide and dried magnesium trisilicate; and

a low moisture content medium chain triglyceride vehicle, wherein the composition is a liquid, the concentration of medium chain triglycerides ranges from about 50% to about 99% (w/v) of the composition, and the composition contains less than about 1.0% (w/v) water.

2. The composition of claim 1, wherein the composition is a suspension.

3. The composition of claim 1, wherein the one or more of silicon dioxide, colloidal silicon dioxide and magnesium trisilicate are dried prior to inclusion in the pharmaceutical composition.

4. The composition of claim 1, wherein the medium chain triglycerides contain less than about 0.1% (w/w) water.

5. The composition of claim 1, wherein the composition is suitable for oral delivery.

6. The composition of claim 1, wherein the β

-lactam antibiotic is a penicillin selected from the group consisting of penicillin G, penicillin V, methicillin, nafcillin, oxacillin, cloxacillin, dicloxacllin, ampicillin, amoxicillin, carbenicillin, ticarcillin, piperacillin, mezlocillin, aziocillin, and mixtures thereof.

7. The composition of claim 1, wherein the β

-lactam antibiotic is amoxicillin.

8. The composition of claim 1, wherein the β

-lactam antibiotic is stable for at least about ten days when stored at a temperature of about 20°

C. to about 25°

C.

9. A method for preparing a pharmaceutical composition for reconstitution, comprising the steps of:

a) drying one or more of silicon dioxide, colloidal silicon dioxide and magnesium trisilicate;

b) mixing a β

-lactam antibiotic and one or more of dried silicon dioxide, dried colloidal silicon dioxide and dried magnesium trisilicate to prepare a powder;

c) placing an amount of the powder sufficient to provide a therapeutically effective amount of the β

-lactam antibiotic into a first container;

d) providing a second container containing a low moisture content medium chain triglyceride vehicle in a quantity sufficient to reconstitute the amount of the powder;

e) packaging the first and second containers together in a kit.

10. A liquid pharmaceutical composition, comprising a β

-lactam antibiotic, one or more dried hygroscopic excipients and a low moisture content medium chain triglyceride vehicle, wherein the composition is a liquid and the composition contains less than about 1.0% (w/v) water.

11. The composition of claim 10, wherein the composition is a suspension.

12. The composition of claim 10, wherein the β

-lactam antibiotic is a penicillin selected from the group consisting of penicillin G, penicillin V, methicillin, nafcillin, oxacillin, cloxacillin, dicloxacllin, ampicillin, amoxicillin, carbenicillin, ticarcillin, piperacillin, mezlocillin, aziocillin, and mixtures thereof.

13. The composition of claim 10, wherein the β

-lactam antibiotic is amoxicillin.

14. The composition of claim 10, wherein the one or more hygroscopic excipients comprise one or more of silicon dioxide, colloidal silicon dioxide and magnesium trisilicate.

15. The composition of claim 10, wherein the hygroscopic excipients are dried prior to inclusion in the pharmaceutical composition.

16. The composition of claim 10, wherein the medium chain triglycerides contain less than about 0.1% (w/w) water.

17. The composition of claim 10, wherein the concentration of medium chain triglycerides is from about 50% (w/v) to about 99% (w/v).

18. The composition of claim 10, wherein the β

-lactam antibiotic is stable for at least about ten days when stored at a temperature of about 20°

C. to about 25°

C.

19. The composition of claim 10, wherein the composition is suitable for oral delivery.

20. A liquid pharmaceutical composition for oral delivery consisting essentially of a β

-lactam antibiotic, one or more of silicon dioxide, colloidal silicon dioxide and magnesium trisilicate, and a low moisture content medium chain triglyceride vehicle, wherein the composition is a liquid, the concentration of medium chain triglycerides ranges from about 50% to about 99% (w/v) of the composition, and the composition contains less than about 1.0% (w/v) water.