COMPOSITION AND METHOD FOR PROTON PUMP INHIBITOR SUSPENSION

• US 20190321348A1
• Filed: 06/16/2017
• Published: 10/24/2019
• Est. Priority Date: 06/16/2016
• Status: Active Grant

• Current Assignee: Azurity Pharmaceuticals, Inc.
• Original Assignee: Cutispharma, Inc. (Azurity Pharmaceuticals, Inc.)
• Inventors: Fallin, Ken, Renaud, Kaity, Mione, Peter, Muni, Neal, Gandhi, Anisa
• Granted Patent: US 11,207,307 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• 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 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Abstract

Suspensions of pump inhibitors (PPIs) are disclosed. The suspension may include a PPI, a copolymer of ethylene oxide and propylene oxide; simethicone emulsion; Sodium Bicarbonate; and Sodium Citrate, USP (Dihydrate). The suspensions have desirable viscosities and enhanced stability.

Claims

1. A suspension of a proton pump inhibitor (PPI), comprising a PPI;

a copolymer of ethylene oxide and propylene oxide;

simethicone emulsion;

Sodium Bicarbonate;

Sodium Citrate, USP (Dihydrate);

a preservative, a thickening agent, a sweetener, and water.

2. The suspension of claim 1, wherein the copolymer of ethylene oxide and propylene oxide is Poloxamer 188.

3. The suspension of claim 1, wherein the thickening agent is xanthan gum.

4. The suspension of claim 1, wherein the thickening agent is hydroxyethylcellulose.

5. The suspension of claim 1, wherein the sweetener is sorbitol.

6. The suspension of claim 1, wherein the preservative is benzyl alcohol.

7. The suspension of claim 1, further comprising propylene glycol.

8. The suspension of claim 1, further comprising FD&

C Red No. 40, Flavor Strawberry 28082, Saccharin Sodium, and Sucralose.

9. The suspension of claim 1, wherein the pH of the formulation is at least pH 8.0.

10. The suspension of claim 1, wherein the formulation retains homogeneity of less than +/−

5% of assay for active pharmaceutical ingredient after at least 30 days.

11. The suspension of claim 1, wherein the dynamic viscosity is greater than or equal to 50 and less than or equal to 1000 centipoise (cP).

12. The suspension of claim 1, wherein the dynamic viscosity is greater than or equal to 40 and less than or equal to 50 centipoise (cP).

13. The suspension of claim 1, wherein the dynamic viscosity is greater than or equal to 200 and less than or equal to 300 centipoise (cP).

14. The suspension of claim 1, wherein the suspension includes the following:

a. 0.5% (w/v) Benzyl Alcohol, NF;

b. 0.003% (w/v) FD&

C Red No. 40;

c. 0.15% (w/v) Flavor Strawberry 28082;

d. 0.35% (w/v) hydroyethylcellulose, NF;

e. 2.00-4.00% (w/v) Poloxamer 188, NF;

f. 5.0% (w/v) Propylene Glycol, USP;

g. 0.2% (w/v) Simethicone Emulsion, USP (30%);

h. 8.4% (w/v) Sodium Bicarbonate, USP, Granular No. 5;

i. 1.0% (w/v) Sodium Citrate, USP (Dihydrate);

j. 0.45% (w/v) Sucralose, NF;

k. 0.4% (w/v) Xanthan Gum, NF; and

l. Purified water, USP.

15. The suspension of claim 1, wherein the suspension includes the following:

a. 0.5% (w/v) Benzyl Alcohol, NF;

b. 0.003% (w/v) FD&

C Red No. 40;

c. 0.15% (w/v) Flavor Strawberry 28082;

d. 0.07% (w/v) Ammonium Glycyrrhizate, NF;

e. 0.25% (w/v) Hydroxyethylcellulose, NF;

f. 2.0% (w/v) Poloxamer 188, USP;

g. 0.08% (w/v) Saccharin Sodium, USP;

h. 0.2% (w/v) Simethicone Emulsion, USP (30%);

i. 8.4% (w/v) Sodium Bicarbonate, USP, Granular No. 5;

j. 1.0% (w/v) Sodium Citrate, USP (Dihydrate);

k. 2.5% (w/v) Sorbitol Solution, USP (70%);

l. 0.4% (w/v) Sucralose, NF; and

m. Purified water, USP.

20. A method of delivering a PPI suspension to a subject, said method comprising passing the suspension of claim 1 through a tube having a diameter of between 5 French and 12 French.

25. The suspension of claim 1, wherein the suspension comprises a pH of at least 8.

26. The suspension of claim 1, wherein the formulation retains homogeneity of less than +/−

5% of assay for active pharmaceutical ingredient after at least 30 days.

27. The suspension of claim 1, wherein the formulation maintains homogeneity of the active pharmaceutical ingredient for at least 30 days after reconstitution.

28. The suspension of claim 1, wherein the suspension includes the following:

0.4%-0.6% (w/v) Benzyl Alcohol, NF;

0.2%-0.5% (w/v) hydroyethylcellulose;

1.0%-6.0% (w/v) Poloxamer 188, NF;

0.1%-0.3% (w/v) Simethicone Emulsion, USP (30%);

8.0%-8.8% (w/v) Sodium Bicarbonate, USP, Granular No. 5;

0.5%-1.5% (w/v) Sodium Citrate, USP (Dihydrate);

0.35%-0.5% (w/v) Sucralose, NF;

1.5%-4% (w/v) Sorbitol solution, and

8%-12% (w/v) Glycerin 99.7%.

29. The suspension of claim 28, wherein the suspension includes the following:

0.4%-0.6% (w/v) Benzyl Alcohol, NF;

0.002%-0.005% (w/v) FD&

C Red No. 40;

0.1%-0.2% (w/v) Flavor Strawberry 28082;

0.2%-0.5% (w/v) hydroyethylcellulose;

1.0%-6.0% (w/v) Poloxamer 188, NF;

0.1%-0.3% (w/v) Simethicone Emulsion, USP (30%);

8.0%-8.8% (w/v) Sodium Bicarbonate, USP, Granular No. 5;

0.5%-1.5% (w/v) Sodium Citrate, USP (Dihydrate);

0.35%-0.5% (w/v) Sucralose, NF;

Purified water, USP

1.5%-4% (w/v) Sorbitol solution, and

8%-12% (w/v) Glycerin 99.7%.

30. The suspension of claim 28, wherein the suspension includes the following:

0.5% (w/v) Benzyl Alcohol, NF;

0.003% (w/v) FD&

C Red No. 40;

0.15% (w/v) Flavor Strawberry 28082;

0.35% (w/v) hydroyethylcellulose;

2.0% (w/v) Poloxamer 188, NF;

0.15% (w/v) Simethicone Emulsion, USP (30%);

8.4% (w/v) Sodium Bicarbonate, USP, Granular No. 5;

1.0% (w/v) Sodium Citrate, USP (Dihydrate);

0.4% (w/v) Sucralose, NF;

Purified water, USP

2.5% (w/v) Sorbitol solution, and

10% (w/v) Glycerin 99.7%.

31. The suspension of claim 28, wherein the suspension includes the following:

0.5% (w/v) Benzyl Alcohol, NF;

0.003% (w/v) FD&

C Red No. 40;

0.15% (w/v) Flavor Strawberry 28082;

0.35% (w/v) hydroyethylcellulose;

4.0% (w/v) Poloxamer 188, NF;

0.15% (w/v) Simethicone Emulsion, USP (30%);

8.4% (w/v) Sodium Bicarbonate, USP, Granular No. 5;

1.0% (w/v) Sodium Citrate, USP (Dihydrate);

0.4% (w/v) Sucralose, NF;

Purified water, USP

2.5% (w/v) Sorbitol solution, and

10% (w/v) Glycerin 99.7%.

16. A liquid diluent comprising:

0.4-0.6% (w/v) Benzyl Alcohol, NF;

0.002-0.005% (w/v) dye;

0.1-0.2% (w/v) flavoring;

0.06-0.08% (w/v) Ammonium Glycyrrhizate, NF;

1.00-3.00% (w/v) Poloxamer 188, NF;

4.0-6.0% (w/v) Propylene Glycol, USP;

0.1-0.3% (w/v) Simethicone Emulsion, USP;

8.0-8.8% (w/v) Sodium Bicarbonate, USP;

0.5-1.5% (w/v) Sodium Citrate, USP (Dihydrate);

0.4-0.45% (w/v) Sucralose, NF;

0.3-0.5% (w/v) Xanthan Gum, NF; and

purified water, USP.

17. The liquid diluent of claim 16, comprising:

0.5% (w/v) Benzyl Alcohol, NF;

0.003% (w/v) FD&

C Red No. 40;

0.15% (w/v) Flavor Strawberry 28082;

0.07% (w/v) Ammonium Glycyrrhizate, NF;

2.00% (w/v) Poloxamer 188, NF;

5.0% (w/v) Propylene Glycol, USP;

0.2% (w/v) Simethicone Emulsion, USP (30%);

8.4% (w/v) Sodium Bicarbonate, USP, Granular No. 5;

1.0% (w/v) Sodium Citrate, USP (Dihydrate);

0.45% (w/v) Sucralose, NF;

0.4% (w/v) Xanthan Gum, NF; and

Purified water, USP.

18-19. -19. (canceled)

21. A suspension of a proton pump inhibitor (PPI), comprising a PPI, a copolymer of ethylene oxide and propylene oxide;

simethicone emulsion;

Sodium Bicarbonate; and

Sodium Citrate, USP (Dihydrate), wherein the suspension is stable for at least 30 days when stored at 2-8 degrees Celsius.

22. A diluent for a proton pump inhibitor (PPI), comprising a copolymer of ethylene oxide and propylene oxide;

simethicone emulsion;

Sodium Bicarbonate; and

Sodium Citrate, USP (Dihydrate), wherein the diluent is stable for at least 24 months when stored between 2 and 25 degrees Celsius.

23. The suspension of claim 22, wherein the diluent is stable for at least 24 months when stored between 2 and 8 degrees Celsius.

24. (canceled)