# US 2018/0021280 A1 · Levodopa and Carbidopa Intestinal Gel and Methods of Use

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- Number: US 2018/0021280 A1
- Document ID: US20180021280A1
- Status: Published application
- Kind: A1
- Application number: 15/655,078
- Filed: 2017-07-20
- Published: 2018-01-25
- Earliest claimed: 2016-07-20
- Assignees: AbbVie Inc.
- Applicants: AbbVie Inc.
- Inventors: Alexandru DEAC; Ye HUANG; John M. LIPARI; Alexander RUGGLES; Thin Yu TUN
- Web page: https://patentgrep.com/patent/US20180021280A1

## CPC

- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61K 9/00: Medicinal preparations characterised by special physical form {(nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12)}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/10: Dispersions; Emulsions
- A61K 31/195: having an amino group
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61K 47/38: Cellulose; Derivatives thereof
- A61P 25/16: Anti-Parkinson drugs
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure provides (a) a pharmaceutical composition comprising a levodopa active agent and a carbidopa active agent and (b) methods of treating Parkinson's disease and associated conditions comprising administering the pharmaceutical composition to a subject with Parkinson's disease.

## Claims

### Claim 1

A pharmaceutical composition for intraduodenal administration comprising:
(a) a levodopa active agent in an amount of about 4.0 w/w % of the total composition;
(b) a carbidopa active agent in an amount of about 1.0 w/w % of the total composition;
(c) a polymer-based suspending agent in an amount of about 0.1 w/w % to about 5 w/w % of the total composition; and
(d) a liquid vehicle,
wherein:
(i) the liquid vehicle is water, polyethylene glycol, or a mixture of water and polyethylene glycol;
(ii) the acceptance value of the pharmaceutical composition is less than or equal to 15 with respect to the levodopa active agent and less than or equal to 15 with respect to the carbidopa active agent; and
(iii) the yield value of the pharmaceutical composition is at least about 0.3 Pa,
wherein:
the acceptance value and yield value are measured after exposing the pharmaceutical composition to a temperature of about 25° C. and relative humidity of about 60% for a period of at least about 8 weeks.

### Claim 2 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the polymer-based suspending agent is a carbomer.

### Claim 3 (depends on 2)

The pharmaceutical composition according to claim 2, wherein the polymer based suspending agent is Carbopol® 971P or Carbopol® 974P.

### Claim 4 (depends on 2)

The pharmaceutical composition according to claim 2, wherein the composition comprises the polymer-based suspending agent in an amount of about 0.1 w/w % to about 0.3 w/w % of the total composition.

### Claim 5 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the polymer based suspending agent is a hydrocolloid polymer.

### Claim 6 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the polymer-based suspending agent is selected from the group consisting of locust beam gum, guar gum, methylcellulose, sodium carboxymethylcellulose with microcrystalline cellulose, xanthan gum, and gum tragacanth.

### Claim 7 (depends on 6)

The pharmaceutical composition according to claim 6, wherein the composition comprises the polymer-based suspending agent in an amount of about 1 w/w % to about 5 w/w % of the total composition.

### Claim 8 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the liquid vehicle is water.

### Claim 9 (depends on 1)

The pharmaceutical composition according to claim 1 comprising:
(a) levodopa in an amount of about 4.0 w/w % of the total composition;
(b) carbidopa monohydrate in an amount of about 1.0 w/w % of the total composition;
(c) Carbopol® 971P or Carbopol® 974P in an amount of about 0.1 w/w % to about 0.2 w/w % of the total composition; and
(d) water.

### Claim 10 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the levodopa active agent has a median particle size distribution (D50) of ≦37 μm.

### Claim 11 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the carbidopa active agent has a median particle size distribution (D50) of about ≦10 μm.

### Claim 12 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the amount of impurities in the pharmaceutical composition is in an amount of less than about 5.8 w/w % of the total weight of the composition when maintained at a temperature of about 20-25° C. and a relative humidity of 60% for a period of at least 15 weeks.

### Claim 13 (depends on 1)

A pharmaceutical dosage form comprising the pharmaceutical composition according to claim 1 in a disposable drug reservoir having an oxygen impermeable enclosure disposed therein, wherein the oxygen impermeable enclosure is purged with an inert gas and an oxygen scavenger is added.

### Claim 14 (depends on 13)

The pharmaceutical dosage form according to claim 13 comprising about 40 mg/mL or the levodopa active agent and about 10 mg/mL of the carbidopa active agent.

### Claim 15 (depends on 9)

A pharmaceutical dosage form comprising the pharmaceutical composition according to claim 9 in a disposable drug reservoir having an oxygen impermeable enclosure disposed therein, wherein the oxygen impermeable enclosure is purged with an inert gas and an oxygen scavenger is added.

### Claim 16

A method of preparing the pharmaceutical composition comprising a levodopa active agent and a carbidopa active agent for intraduodenal administration, wherein
(i) the pharmaceutical composition has an acceptance value of the pharmaceutical composition is less than or equal to 15 with respect to the levodopa active agent and less than or equal to 15 with respect to the carbidopa active agent; and
(ii) the pharmaceutical composition has a yield value of at least about 0.3 Pa,
wherein:
the acceptance value and yield value are measured after exposing the pharmaceutical composition to a temperature of about 25° C. and relative humidity of about 60% for a period of at least about 8 weeks,
the method comprising:
adding a acrylic acid-based polymer suspending agent to water to form a dispersion;
adding a neutralizing agent to the dispersion to bring the pH to about 6.5 to form a medium;
adding a levodopa active agent and a carbidopa active agent to water to form a slurry; and
adding the slurry to the medium to form the pharmaceutical composition.

### Claim 17 (depends on 16)

The pharmaceutical composition according to claim 16, wherein the acrylic acid-based polymer suspending agent is Carbopol® 971P or Carbopol® 974P.

### Claim 18

A method of preparing the pharmaceutical composition comprising a levodopa active agent and a carbidopa active agent for intraduodenal administration, wherein
(i) the pharmaceutical composition has an acceptance value of the pharmaceutical composition is less than or equal to 15 with respect to the levodopa active agent and less than or equal to 15 with respect to the carbidopa active agent; and
(ii) the pharmaceutical composition has a yield value of at least about 0.3 Pa,
wherein:
the acceptance value and yield value are measured after exposing the pharmaceutical composition to a temperature of about 25° C. and relative humidity of about 60% for a period of at least about 8 weeks,
the method comprising:
adding a hydrocolloid polymer suspending agent to water to form a dispersion;
adding a levodopa active agent and a carbidopa active agent to water to form a slurry; and
adding the slurry to the medium to form the pharmaceutical composition.

### Claim 19 (depends on 18)

The pharmaceutical composition according to claim 18, wherein the polymer-based suspending agent is selected from the group consisting of locust beam gum, guar gum, sodium carboxymethylcellulose with microcrystalline cellulose, xanthan gum, and gum tragacanth.

### Claim 20 (depends on 1)

A method of treating Parkinson's disease in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition according to claim 1.