# US 11,110,085 B2 · Co-spray drying of ciprofloxacin and colistin and the uses thereof

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- Number: US 11,110,085 B2
- Document ID: US11110085B2
- Status: Granted
- Kind: B2
- Application number: 16/395,302
- Filed: 2019-04-26
- Published: 2019-10-31
- Granted: 2021-09-07
- Earliest claimed: 2018-04-26
- Assignees: Purdue Research Foundation
- Applicants: Purdue Research Foundation
- Inventors: Qi Zhou; Nivedita Shetty
- Web page: https://patentgrep.com/patent/US11110085B2

## CPC

- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 9/0075: {for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles}
- A61K 9/1617: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/1694: {resulting in granules or microspheres of the matrix type containing more than 5% of excipient}
- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## 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

### Claim 1

A process for manufacturing a dry powder composition consisting of leucine, dual antibiotics of a polymycin and a quinolone, comprising the steps of
a. dissolving leucine, a polymyxin compound and a quinolone compound, or a pharmaceutically acceptable salts 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 to afford said dry powder composition of dual antibiotics with an improved inhalable fraction of said antibiotics and an increased physical stability and aerosolization stability as compared with quinolone alone.

### Claim 2 (depends on 1)

The process of claim 1, wherein said leucine comprises about 10% to 60% of the total solid weight.

### Claim 3 (depends on 1)

The process of claim 1, wherein said polymyxin is colistin or a pharmaceutically acceptable salt thereof, and said quinolone is ciprofloxancin or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The process of claim 1, 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.

### Claim 5 (depends on 1)

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 polymyxin and quinolone compounds which could not be fully dissolved in pure water.

### Claim 6 (depends on 1)

A dry powder composition manufactured according to the process of claim 1, wherein said leucine comprises about 10% to 60% of the total solid weight of leucine, polymyxin and quinolone compounds mixture.

### Claim 7 (depends on 1)

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

### Claim 8 (depends on 2)

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

### Claim 9

A pharmaceutical composition consisting of leucine and dual antibiotics of a polymycin and a quinolone manufactured according to a process of:
a. dissolving leucine, said polymycin and said quinolone, or pharmaceutically acceptable salts thereof, 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 to afford said pharmaceutical composition of dual antibiotics with an improved inhalable fraction of said antibiotics and an increased physical stability and aerosolization stability as compared with quinolone alone.

### Claim 10 (depends on 9)

The pharmaceutical composition manufactured according to claim 9, wherein said leucine comprises about 10% to 60% of the total solid weight of leucine, said polymycin and said quinolone mixture.

### Claim 11 (depends on 9)

The pharmaceutical composition manufactured according to claim 9, wherein said solution comprises about 5 to 200 mg of said polymycin and said quinolone per milliliter.

### Claim 12 (depends on 11)

The pharmaceutical composition manufactured according to claim 11, wherein said polymycin and said quinolone are in a ratio of about 1:10 to about 10:1 (weight/weight).

### Claim 13 (depends on 9)

The pharmaceutical composition manufactured according claim 9 is administered by inhalation.

### Claim 14

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 consisting of leucine, a quinolone, and a polymycin is manufactured according to a process comprising the steps of
a. dissolving said leucine, polymycin and quinolone antibiotics, or pharmaceutically acceptable salts thereof, 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 to afford said pharmaceutical composition of dual antibiotics of said polymycin and said quinolone with an improved inhalable fraction of said antibiotics and an increased physical stability and aerosolization stability as compared with quinolone alone.

### Claim 15 (depends on 14)

The method according to claim 14, wherein said leucine comprises about 10% to 60% of the total solid weight of leucine, said polymycin and said quinolone mixture.

### Claim 16 (depends on 14)

The method according to claim 14, wherein said polymycin is colistin or a pharmaceutically acceptable salt thereof, and said quinolone is ciprofloxancin or a pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 14)

The method according to claim 14, wherein said infection is an infection of the lungs.

### Claim 18 (depends on 14)

The method according to claim 14, wherein said infection is caused by Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae.

### Claim 19 (depends on 14)

The method according to claim 14, wherein said pharmaceutical composition is administered by inhalation.