# US 12,109,188 B1 · Liquid pharmaceutical formulations of topiramate

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- Number: US 12,109,188 B1
- Document ID: US12109188B1
- Status: Granted
- Kind: B1
- Application number: 18/126,221
- Filed: 2023-03-24
- Published: 2024-10-03
- Granted: 2024-10-08
- Earliest claimed: 2023-03-24
- Applicants: TaP Pharmaceuticals AG
- Inventors: Nilesh Parikh; William Hite
- Web page: https://patentgrep.com/patent/US12109188B1

## CPC

- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 31/36: Compounds containing methylenedioxyphenyl groups, e.g. sesamin
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- 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)}
- A61K 9/10: Dispersions; Emulsions
- A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin}
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- 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

Certain embodiments of the present disclosure provide liquid pharmaceutical formulations, suitable for oral administration, that contain a therapeutically effective amount of topiramate that is from 50 mg/ml to 100 mg/ml and amounts of polyethylene glycol (“PEG”) 400 and glycerol sufficient to result in a greater than a prior art taught calculated maximum amount of the topiramate being in the solution phase of the formulation, at room temperature.

## Claims

### Claim 1

A liquid pharmaceutical formulation, suitable for oral administration, that consists of a therapeutically effective amount of topiramate and:
(a) 10% w/w polyethylene glycol (“PEG”) 400 and a quantity of glycerol, from 72.5% w/w to 86% w/w, that brings the formulation to 100% w/w, wherein from 25 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation;
(b) 15% w/w PEG 400 and a quantity of glycerol, from 67.5% w/w to 81% w/w, that brings the formulation to 100% w/w, wherein from 32.5 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation;
(c) 20% w/w PEG 400 and a quantity of glycerol, from 62.5% w/w to 76% w/w, that brings the formulation to 100% w/w, wherein from 40 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation; or
(d) 25% w/w PEG 400 and a quantity of glycerol, from 57.5% w/w to 71% w/w, that brings the formulation to 100% w/w, wherein from 47.5 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation.

### Claim 2 (depends on 1)

A method of making the formulation of claim 1, consisting of: mixing the PEG 400, the glycerol, and the topiramate to form a suspension or clear solution.

### Claim 3 (depends on 2)

The method of claim 2, wherein when a suspension results from the mixing, the formulation is heated to between 40° C. and 100° C. until a clear solution is obtained.

### Claim 4 (depends on 2)

The method of claim 2, wherein the topiramate is mixed with the PEG 400 to form a suspension or a clear solution and then the glycerol is mixed with the suspension or the clear solution of PEG 400 and topiramate.

### Claim 5 (depends on 4)

The method of claim 4, wherein when a suspension results from mixing the topiramate and the PEG 400, the mixture of the topiramate and the PEG 400 is heated to between 40° C. and 100° C. until a clear solution is obtained or the mixture of the topiramate, PEG 400, and the glycerol is heated to between 40° C. and 100° C. until a clear solution is obtained.

### Claim 6 (depends on 1)

A method of treating one or more of conditions: (i) partial-onset tonic-clonic seizures, (ii) primary generalized tonic-clonic seizures, or (iii) seizures associated with Lennox-Gastaut syndrome, comprising orally administering the formulation of claim 1 to a subject presenting one or more of conditions (i), (ii), and (iii).

### Claim 7

A liquid pharmaceutical formulation, suitable for oral administration, that consists of about 4% w/w to about 8% w/w topiramate and:
(a) 10% w/w PEG 400 and a quantity of glycerol, from 81% w/w to 86% w/w, that brings the formulation to 100% w/w, wherein from 25 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation;
(b) 15% w/w PEG 400 and a quantity of glycerol, from 76% w/w to 81% w/w, that brings the formulation to 100% w/w, wherein from 32.5 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation;
(c) 20% w/w PEG 400 and a quantity of glycerol, from 71% w/w to 76% w/w, that brings the formulation to 100% w/w, wherein from 40 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation; or
(d) 25% w/w PEG 400 and a quantity of glycerol, from 65% w/w to 69% w/w, that brings the formulation to 100% w/w, wherein from 47.5 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation.

### Claim 8 (depends on 7)

A method of making the formulation of claim 7, consisting of: mixing the glycerol, the PEG 400, and the topiramate to form a suspension or clear solution.

### Claim 9 (depends on 8)

The method of claim 8, wherein when a suspension results from the mixing, the formulation is heated to between 40° C. and 100° ° C. until a clear solution is obtained.

### Claim 10 (depends on 9)

The method of claim 9, wherein the topiramate is mixed with the PEG 400 to form a suspension or a clear solution and then the glycerol is mixed with the suspension or the clear solution of PEG 400 and topiramate.

### Claim 11 (depends on 10)

The method of claim 10, wherein when a suspension results from mixing the topiramate and the PEG 400, the mixture of the topiramate and the PEG 400 is heated to between 40° C. and 100° C. until a clear solution is obtained or the mixture of the topiramate, PEG 400, and the glycerol is heated to between 40° C. and 100° C. until a clear solution is obtained.

### Claim 12 (depends on 7)

A method of treating one or more of conditions: (i) partial-onset tonic-clonic seizures, (ii) primary generalized tonic-clonic seizures, or (iii) seizures associated with Lennox-Gastaut syndrome, comprising orally administering the formulation of claim 7 to a subject presenting one or more of conditions (i), (ii), and (iii).

### Claim 13

A liquid pharmaceutical formulation, suitable for oral administration, that consists of a therapeutically effective amount of topiramate, from 0.01% w/w to 2.0% w/w of a sweetener, from 0.01% w/w to 2.0% w/w of a flavorant, or a combination the sweetener and the flavorant, and:
(a) 10% w/w polyethylene glycol (“PEG”) 400 and a quantity of glycerol, from 72.5% w/w to 86% w/w, that brings the formulation to 100% w/w, wherein from 25 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation;
(b) 15% w/w PEG 400 and a quantity of glycerol, from 67.5% w/w to 81% w/w, that brings the formulation to 100% w/w, wherein from 32.5 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation;
(c) 20% w/w PEG 400 and a quantity of glycerol, from 62.5% w/w to 76% w/w, that brings the formulation to 100% w/w, wherein from 40 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation; or
(d) 25% w/w PEG 400 and a quantity of glycerol, from 57.5% w/w to 71% w/w, that brings the formulation to 100% w/w, wherein from 47.5 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation.

### Claim 14 (depends on 13)

The formulation of claim 13, wherein the sweetener is sucrose.

### Claim 15 (depends on 13)

The formulation of claim 13, wherein the flavorant is a berry.

### Claim 16 (depends on 13)

The formulation of claim 13, wherein the formulation further consists of the sweetener and the flavorant, wherein the sweetener is sucrose and the flavorant is a berry.

### Claim 17

A liquid pharmaceutical formulation, suitable for oral administration, that consists of about 4% w/w to about 8% w/w topiramate, and:
(a) 10% w/w PEG 400 and a quantity of glycerol, from 81% w/w to 86% w/w, that brings the formulation to 100% w/w, wherein from 25 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation;
(b) 15% w/w PEG 400 and a quantity of glycerol, from 76% w/w to 81% w/w, that brings the formulation to 100% w/w, wherein from 32.5 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation;
(c) 20% w/w PEG 400 and a quantity of glycerol, from 71% w/w to 76% w/w, that brings the formulation to 100% w/w, wherein from 40 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation; or
(d) 25% w/w PEG 400 and a quantity of glycerol, from 65% w/w to 69% w/w, that brings the formulation to 100% w/w, wherein from 47.5 mg/ml to 70 mg/ml of the topiramate is, at room temperature, in the solution phase of the formulation,
wherein each of (a), (b), (c), and (d) further consist of: (i) from 0.01% w/w to 2.0% w/w of a sweetener, (ii) from 0.01% w/w to 2.0% w/w of a flavorant, or (iii) a combination of the sweetener and the flavorant.

### Claim 18 (depends on 17)

The formulation of claim 17, wherein the sweetener is sucrose.

### Claim 19 (depends on 17)

The formulation of claim 17, wherein the flavorant is a berry.

### Claim 20 (depends on 17)

The formulation of claim 17, wherein the formulation consists of the sweetener and the flavorant, wherein the sweetener is sucrose and the flavorant is a berry.