NOVEL PHARMACEUTICAL DOSAGE FORMS COMPRISING VALGANCICLOVIR HYDROCHLORIDE

• US 20150057296A1
• Filed: 10/31/2014
• Published: 02/26/2015
• Est. Priority Date: 12/13/2006
• Status: Active Grant

• Current Assignee: Cheplapharm Arzneimittel GmbH
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Bachynsky, Maria Oksana, Infeld, Martin Howard, Shah, Navnit Hargovindas
• Granted Patent: US 9,642,911 B2
• Time in Patent Office: Days
• US Class Current: 514/263.38
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• 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 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: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/22 for herpes viruses

Abstract

The present invention provides novel solid pharmaceutical dosage forms for oral administration, after being constituted in water. The solid dosage forms comprise a therapeutically effective amount of valganciclovir hydrochloride and a non-hygroscopic organic acid present in an amount sufficient to stabilize the valganciclovir hydrochloride in a predetermined amount of water. The present invention also provides novel liquid pharmaceutical dosage forms for oral administration after constituting the solid pharmaceutical dosage form with water. A non-hygroscopic bulking agent may optionally be included in the above dosage form. These novel pharmaceutical dosage forms are useful in the treatment or control of viruses such as herpes simplex virus and cytomegalovirus. The present invention also provides a method for treating these diseases employing the solid and liquid pharmaceutical dosage forms and a method for preparing these pharmaceutical dosage forms.

Claims

1. A solid pharmaceutical dosage form for oral administration, after being constituted in water, comprising:

(a) a therapeutically effective amount of valganciclovir hydrochloride; and

(b) a non-hygroscopic organic acid present in an amount sufficient to stabilize the valganciclovir hydrochloride in a predetermined amount of water.

2. The solid dosage form according to claim 1, wherein valganciclovir hydrochloride is present in an amount from about 10% to about 90%, by weight of the total composition.

3. The solid dosage form according to claim 1, wherein the non-hygroscopic organic acid is selected from the group consisting of fumaric acid, succinic acid, and adipic acid.

4. The solid dosage form according to claim 3, wherein the non-hygroscopic organic acid is fumaric acid.

5. The solid dosage form according to claim 1, wherein the non-hygroscopic organic acid is aspartic acid or glutamic acid.

6. The solid dosage form according to claim 1, further comprising an effective amount of a non-hygroscopic bulking agent.

7. The solid dosage form according to claim 6, wherein the non-hygroscopic bulking agent is selected from the group consisting of mannitol and lactose.

8. The solid dosage form according to claim 7, wherein the non-hygroscopic bulking agent is mannitol.

9. The solid dosage form according to claim 6, wherein the non-hygroscopic bulking agent is present in an amount up to about 90% by weight of the total composition.

10. The solid dosage form according to claim 1, wherein the dosage form has the following composition:

11. A liquid pharmaceutical dosage form for oral administration comprising:

(a) a therapeutically effective amount of valganciclovir hydrochloride;

(b) a predetermined amount of water; and

(c) a non-hygroscopic organic acid present in an amount sufficient to stabilize the valganciclovir hydrochloride in the predetermined amount of water.

12. The liquid dosage form according to claim 11, wherein valganciclovir hydrochloride is present in an amount from about 10 mg/mL to about 90 mg/mL.

13. The liquid dosage form according to claim 11, wherein the non-hygroscopic organic acid is selected from the group consisting of fumaric acid, succinic acid, and adipic acid.

14. The liquid dosage form according to claim 13, wherein the non-hygroscopic organic acid is fumaric acid.

15. The liquid dosage form according to claim 11, wherein the non-hygroscopic organic acid is an amino acid.

16. The liquid dosage form according to claim 11, wherein the non-hygroscopic organic acid is present in the liquid dosage form in an amount sufficient to lower the pH to 3.8 or below.

17. The liquid dosage form according to claim 11, further comprising an effective amount of a non-hygroscopic bulking agent.

18. The liquid dosage form according to claim 17, wherein the non-hygroscopic bulking agent is selected from the group consisting of mannitol and lactose.

19. The liquid dosage form according to claim 18, wherein the non-hygroscopic bulking agent is mannitol.

20. The liquid dosage form according to claim 17, wherein the non-hygroscopic bulking agent is present in an amount up to about 90% by weight of the total composition.

21. The liquid dosage form according to claim 11, wherein the dosage form has the following composition:

22. A method of treating a subject infected with a virus selected from the group consisting of herpes simplex virus and cytomegalovirus comprising administering to a patient, in need thereof, a therapeutically effective amount of a liquid pharmaceutical dosage form for oral administration comprising:

(a) a therapeutically effective amount of valganciclovir hydrochloride;

(b) a predetermined amount of water; and

(c) a non-hygroscopic organic acid present in an amount sufficient to stabilize the valganciclovir hydrochloride in the predetermined amount of water.

23. The method according to claim 22, wherein valganciclovir hydrochloride is present in an amount from about 10 mg/mL to about 90 mg/mL and the non-hygroscopic organic acid is present in the liquid dosage form in an amount sufficient to lower the pH to 3.8 or below.

24. The method according to claim 22 wherein the non-hygroscopic organic acid is fumaric acid.

25. The method according to claim 22, further comprising an effective amount of a non-hygroscopic bulking agent selected from the group consisting of mannitol and lactose.