CO-SPRAY DRYING OF CIPROFLOXACIN AND COLISTIN AND THE USES THEREOF

• US 20190328728A1
• Filed: 04/26/2019
• Published: 10/31/2019
• Est. Priority Date: 04/26/2018
• Status: Active Grant

• Current Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Original Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Inventors: Zhou, Qi, Shetty, Nivedita
• Granted Patent: US 11,110,085 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient

Abstract

The present disclosure generally relates to a combination dry powder inhaler (DPI) formulation of Ciprofloxacin and Colistin through co-spray drying, particularly to a co-sprayed colistin and Ciprofloxacin dry powder inhaler for the treatment of various bacterial infections. Methods of use and composition matters are within the scope of this disclosure.

Claims

1. A process for manufacturing a dry powder composition comprising the steps of

a. dissolving a polymyxin compound and a quinolone compound, or a pharmaceutically acceptable salt thereof, respectively, in an aqueous or an organic medium to prepare a solution;

b. adding one or more pharmaceutically acceptable excipients to said solution; and

c. spray-drying of said solution.

2. The process of claim 1 further comprising a step of adding leucine to the solution of colistin and ciprofloxacin, wherein said leucine comprises about 10% to 60% of the total solid weight of leucine/polymyxin/quinolone mixture.

3. The process of claim 2, wherein said polymyxin is colistin or a pharmaceutically acceptable salt thereof, and said quinolone drug is ciprofloxancin or a pharmaceutically acceptable salt thereof.

4. The process of claim 3, wherein said solution comprises about 5 to 200 mg of colistin and ciprofloxacin in a ratio of about 1:

10 to about 10;

1 (weight/weight) per milliliter.

5. The process of claim 3, wherein said leucine comprises about 10% to 60% of the total solid weight of leucine/colistin/ciprofloxacin mixture.

6. The process of claim 1, wherein said aqueous medium is water or an aqueous solution of an organic solvent selected from the group consisting of acetonitrile, methanol, ethanol, or isopropyl alcohol wherein said organic solvent is to improve the solubility of drug material colistin/ciprofloxacin which could not be fully dissolved in pure water.

7. A dry powder composition manufactured according to the process of claim 2, wherein said leucine comprises about 10% to 60% of the total solid weight of leucine/polymyxin/quinolone mixture.

8. A pharmaceutical composition comprising a product manufactured according to the process of claim 1 together with one or more pharmaceutically acceptable excipients.

9. A pharmaceutical composition comprising a product manufactured according to the process of claim 2 together with one or more pharmaceutically acceptable excipients.

10. A pharmaceutical composition manufactured according to a process of:

a. dissolving colistin and ciprofloxacin in an aqueous or an organic medium to prepare a solution;

b. adding one or more pharmaceutically acceptable excipients to said solution; and

c. spray-drying of said solution.

11. The pharmaceutical composition manufactured according to claim 10, wherein said process further comprising a step of adding leucine to the solution of colistin and ciprofloxacin, wherein said leucine comprises about 10% to 60% of the total solid weight of leucine/colistin/ciprofloxacin mixture.

12. The pharmaceutical composition manufactured according to claim 10, wherein said solution comprises about 5 to 200 mg of colistin and ciprofloxacin per milliliter.

13. The pharmaceutical composition manufactured according to claim 12, wherein colistin and ciprofloxacin are in a ratio of about 1:

10 to about 10;

1 (weight/weight)

14. The pharmaceutical composition manufactured according claim 10 is administered by inhalation.

15. A method for treating a patient with a bacterial infection comprising the step of administering a therapeutically effective amount of a pharmaceutical composition to a patient in need of relief from said infection, wherein said pharmaceutical composition is manufactured according to a process comprising the steps of

a. dissolving colistin and ciprofloxacin in an aqueous or an organic medium to prepare a solution;

b. adding one or more pharmaceutically acceptable excipients to said solution; and

c. spray-drying of said solution.

16. The method according to claim 15, wherein said process further comprising a step of adding leucine to the solution of colistin and ciprofloxacin, wherein said leucine comprises about 10% to 60% of the total solid weight of leucine/colistin/ciprofloxacin mixture.

17. The method according to claim 16, wherein said infection is an infection of the lungs.

18. The method according to claim 15, wherein said infection is an infection of the lungs.

19. The method according to claim 15, wherein said infection is caused by Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae.

20. The method according to claim 15, wherein said pharmaceutical composition is administered by inhalation.