Formulation of doxylamine and pyridoxine and/or metabolites or salts thereof

• US 9,089,489 B2
• Filed: 03/27/2014
• Issued: 07/28/2015
• Est. Priority Date: 02/22/2012
• Status: Active Grant

• Current Assignee: Duchesnay Incorporated
• Original Assignee: Duchesnay Incorporated
• Inventors: Vranderick, Manon, St-Onge, Jean-Luc, Gedeon, Christelle, Gallo, Michele, Gervais, ric
• Primary Examiner(s): Vu, Jake
• Application Number:
  US14/228,228
• Publication Number:
  US 20140314680A1
• Time in Patent Office: 488 Days
• Field of Search: 424/468
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4402 only substituted in position 2, e.g. pheniramine, bisacodyl
• CPC Class Codes: A61K 31/4415 Pyridoxine, i.e. Vitamin B6 pyridoxal phosphate A61K31/675
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 11/14 Antitussive agents

Abstract

A dual release oral dosage system/dosage form comprising an immediate release component/composition and a delayed release component/composition is described. Each of the immediate release component/composition and delayed release component/composition comprises one or more of doxylamine, an analog thereof, a derivative thereof, a prodrug thereof, a metabolite thereof and/or a salt thereof, and one or more of pyridoxine, a salt thereof, a metabolite thereof and/or a salt of the metabolite. The dual release oral dosage system/dosage form exhibits an improved pharmacokinetic profile relative to the current Diclectin® formulation and is useful for example for the alleviation of the symptoms of nausea and vomiting, for example in the case of nausea and vomiting in pregnancy (NVP).

Claims

1. A dual release oral dosage form comprising:

(A) an immediate release composition comprising;

(a) from about 5 mg to about 20 mg of doxylamine and/or a pharmaceutically acceptable salt thereof; and

(b) from about 5 mg to about 20 mg of pyridoxine and/or a pharmaceutically acceptable salt thereof; and

(B) a delayed release composition comprising;

(a) from about 5 mg to about 20 mg of doxylamine and/or a pharmaceutically acceptable salt thereof; and

(b) from about 5 mg to about 20 mg of pyridoxine and/or a pharmaceutically acceptable salt thereof;

wherein said immediate release composition is for effecting release of (a) doxylamine and/or pharmaceutically acceptable salt thereof and (b) pyridoxine and/or pharmaceutically acceptable salt thereof, which begins prior to release of (a) doxylamine and/or pharmaceutically acceptable salt thereof and (b) pyridoxine and/or pharmaceutically acceptable salt thereof, from the delayed release component, within the gastrointestinal tract.

2. The dual release oral dosage form of claim 1, wherein said immediate release composition is for effecting release substantially within the stomach.

3. The dual release oral dosage form of claim 1, wherein said delayed release composition is for effecting release substantially within the intestine, and there is substantially no release from said delayed release composition in the stomach.

4. The dual release oral dosage form of claim 1, wherein said dosage form comprises from about 10 mg to about 20 mg of doxylamine and/or pharmaceutically acceptable salt thereof.

5. The dual release oral dosage form of claim 4, wherein said dosage form comprises about 20 mg of doxylamine and/or pharmaceutically acceptable salt thereof.

6. The dual release oral dosage form of claim 1, wherein said dosage form comprises from about 10 mg to about 25 mg of pyridoxine and/or pharmaceutically acceptable salt thereof.

7. The dual release oral dosage form of claim 6, wherein said dosage form comprises from about 10 mg to about 20 mg of pyridoxine and/or pharmaceutically acceptable salt thereof.

8. The dual release oral dosage form of claim 7, wherein said dosage form comprises about 20 mg of pyridoxine and/or pharmaceutically acceptable salt thereof.

9. The dual release oral dosage form of claim 1, wherein said dosage form comprises an identifying characteristic for correlation with its administration in a dosage regimen.

10. The dual release oral dosage form of claim 9, where said identifying characteristic is shape, color, an identifying mark, or any combination thereof.

11. The dual release oral dosage form of claim 1, wherein said dual release oral dosage form comprises (a) a core comprising said delayed release composition and (b) one or more coats substantially surrounding said core, said one or more coats comprising said immediate release composition.

12. The dual release oral dosage form of claim 11, wherein said core is coated with an enteric material.

13. The dual release oral dosage form of claim 1, wherein said immediate release composition is not in contact with said delayed release composition, within said dual release oral dosage form.

14. The dual release oral dosage form of claim 1, wherein said immediate release composition, delayed release composition, or both, further comprise at least one pharmaceutically acceptable carrier or excipient.

15. The dual release oral dosage form of claim 1, where said immediate release composition comprises a pharmaceutically acceptable doxylamine salt and a pharmaceutically acceptable pyridoxine salt.

16. The dual release oral dosage form of claim 1, wherein said delayed release composition comprises a pharmaceutically acceptable doxylamine salt and a pharmaceutically acceptable pyridoxine salt.

17. The dual release oral dosage form of claim 1, where said dual release oral dosage form is a tablet.

18. The dual release oral dosage form of claim 1, wherein the amount of doxylamine and/or pharmaceutically acceptable salt thereof comprised in the immediate release component or composition is substantially equivalent to the amount of doxylamine and/or pharmaceutically acceptable salt thereof comprised in the delayed release component or composition.

19. The dual release oral dosage form of claim 1, wherein the amount of pyridoxine and/or pharmaceutically acceptable salt thereof comprised in the immediate release component or composition is substantially equivalent to the amount of pyridoxine and/or pharmaceutically acceptable salt thereof comprised in the delayed release component or composition.

20. The dual release oral dosage form of claim 1, wherein said pharmaceutically acceptable doxylamine salt is doxylamine succinate.

21. The dual release oral dosage form of claim 1, wherein said pharmaceutically acceptable pyridoxine salt is pyridoxine hydrochloride.

22. The dual release oral dosage form of claim 1, wherein said immediate release composition comprises about 10 mg of doxylamine succinate and about 10 mg of pyridoxine hydrochloride, and said delayed release composition comprises about 10 mg of doxylamine succinate and about 10 mg of pyridoxine hydrochloride.

23. A method for alleviating the symptoms of nausea and vomiting in a mammal, said method comprising administering the dual release oral dosage form of claim 1 to a mammal in need thereof.

24. A method for alleviating the symptoms of nausea and vomiting of human pregnancy, said method comprising administering dual release oral dosage form of claim 1 to a pregnant human female in need thereof.

25. The method of claim 23, wherein said dual release oral dosage form is administered under fasted conditions.

26. The method of claim 24, wherein said dual release oral dosage form is administered under fasted conditions.

27. The method of claim 23, wherein said dual release oral dosage form is administered under fed conditions.

28. The method of claim 24, wherein said dual release oral dosage form is administered under fed conditions.

29. The method of claim 23, wherein said dual release oral dosage form is administered twice-a-day.

30. The method of claim 24, wherein said dual release oral dosage form is administered twice-a-day.