Composition for the management of nausea and vomiting
View Patent ↗A pharmaceutical dosage system comprising (a) an effective amount of one or more of Doxylamine, an analog thereof, a derivative thereof, a prodrug thereof, a metabolite thereof and/or a salt thereof; (b) an effective amount of one or more of (i) Pyridoxine, (ii) an analog thereof, (iii) a derivative thereof, (iv) a prodrug thereof, (v) a metabolite thereof and (vi) a salt of any of (i)-(v); and (c) an effective amount of one or more compounds of formula (I) wherein R is H, PO 3 - or The system exhibits an improved pharmacokinetic profile relative to the current Diclectin®/Diclegis® 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 of pregnancy (NVP).
1. A method for alleviating the symptoms of nausea and vomiting in a human subject, said method comprising administering to a human subject in need thereof pharmaceutical dosage form comprising the following (I) or (II):
(I)
(A) a core consisting of:
(a) about 10 mg of Doxylamine or a pharmaceutically acceptable salt thereof;
(b) about 10 mg of Pyridoxine or a pharmaceutically acceptable salt thereof; and
(c) about 40 mg of a riboflavin compound selected from riboflavin, riboflavin-5-phosphate and flavin adenine dinucleotide, or a pharmaceutically acceptable salt thereof; and
(d) one or more pharmaceutically acceptable excipients;
(B) a delayed release coating surrounding said core;
(C) an immediate release component surrounding said delayed release coating and consisting of:
(a) about 10 mg of Doxylamine or a pharmaceutically acceptable salt thereof;
(b) about 10 mg of Pyridoxine or a pharmaceutically acceptable salt thereof; and
(c) one or more pharmaceutically acceptable excipients and/or coatings; or
(II)
(A) a core consisting of the following ingredients:
(a) about 10 mg of Doxylamine or a pharmaceutically acceptable salt thereof;
(b) about 10 mg of Pyridoxine or a pharmaceutically acceptable salt thereof; and
(c) one or more pharmaceutically acceptable excipients;
(B) a delayed release coating surrounding said core;
(C) an immediate release component surrounding said delayed release coating and consisting of:
(a) about 10 mg of Doxylamine or a pharmaceutically acceptable salt thereof;
(b) about 10 mg of Pyridoxine or a pharmaceutically acceptable salt thereof;
(c) about 40 mg of a riboflavin compound selected from riboflavin, riboflavin-5-phosphate and flavin adenine dinucleotide, or a pharmaceutically acceptable salt thereof; and
(d) one or more pharmaceutically acceptable excipients and/or coatings.
2. The method of claim 1 , wherein said subject is a pregnant female and said method is for alleviating the symptoms of nausea and vomiting of human pregnancy (NVP) in said subject.
3. The method of claim 1 , wherein the riboflavin compound is riboflavin.
4. The method of claim 1 , wherein the riboflavin compound is riboflavin-5-phosphate.
5. The method of claim 1 , wherein the riboflavin compound is flavin adenine dinucleotide.
6. The method of claim 1 , wherein said Doxylamine or pharmaceutically acceptable salt thereof is Doxylamine succinate.
7. The method of claim 1 , wherein said Pyridoxine or pharmaceutically acceptable salt thereof is Pyridoxine hydrochloride.
8. The method of claim 1 , wherein said dosage form is in the form of a tablet, a pill, or a capsule.
9. The method of claim 8 , wherein said dosage form is in the form of a tablet.
10. The method of claim 1 , wherein:
(a) the Doxylamine or pharmaceutically acceptable salt thereof is Doxylamine succinate;
(b) the Pyridoxine or pharmaceutically acceptable salt thereof is Pyridoxine hydrochloride; and
(c) the riboflavin compound is riboflavin.
11. The method of claim 1 , wherein said dosage form comprises:
(I)
(A) a core consisting of:
(a) about 10 mg of Doxylamine or a pharmaceutically acceptable salt thereof;
(b) about 10 mg of Pyridoxine or a pharmaceutically acceptable salt thereof;
(c) about 40 mg of a riboflavin compound selected from riboflavin, riboflavin-5-phosphate and flavin adenine dinucleotide, or a pharmaceutically acceptable salt thereof; and
(d) one or more pharmaceutically acceptable excipients;
(B) a delayed release coating surrounding said core;
(C) an immediate release component surrounding said delayed release coating and consisting of:
(a) about 10 mg of Doxylamine or a pharmaceutically acceptable salt thereof;
(b) about 10 mg of Pyridoxine or a pharmaceutically acceptable salt thereof; and
(c) one or more pharmaceutically acceptable excipients and/or coatings.
12. The method of claim 1 , wherein said dosage form comprises:
(II)
(A) a core consisting of the following ingredients:
(a) about 10 mg of Doxylamine or a pharmaceutically acceptable salt thereof;
(b) about 10 mg of Pyridoxine or a pharmaceutically acceptable salt thereof; and
(c) one or more pharmaceutically acceptable excipients;
(B) a delayed release coating surrounding said core;
(C) an immediate release component surrounding said delayed release coating and consisting of:
(a) about 10 mg of Doxylamine or a pharmaceutically acceptable salt thereof;
(b) about 10 mg of Pyridoxine or a pharmaceutically acceptable salt thereof;
(c) about 40 mg of a riboflavin compound selected from riboflavin, riboflavin-5-phosphate and flavin adenine dinucleotide, or a pharmaceutically acceptable salt thereof; and
(d) one or more pharmaceutically acceptable excipients and/or coatings.
13. The method of claim 1 , wherein a coating surrounds said delayed release coating.
14. The method of claim 2 , wherein the riboflavin compound is riboflavin.
15. The method of claim 2 , wherein the riboflavin compound is riboflavin-5-phosphate.
16. The method of claim 2 , wherein the riboflavin compound is flavin adenine dinucleotide.
17. The method of claim 2 , wherein said Doxylamine or pharmaceutically acceptable salt thereof is Doxylamine succinate.
18. The method of claim 2 , wherein said Pyridoxine or pharmaceutically acceptable salt thereof is Pyridoxine hydrochloride.
19. The method of claim 2 , wherein said dosage form is in the form of a tablet, a pill, or a capsule.
20. The method of claim 2 , wherein said dosage form is in the form of a tablet.
21. The method of claim 2 , wherein:
(a) the Doxylamine or pharmaceutically acceptable salt thereof is Doxylamine succinate;
(b) the Pyridoxine or pharmaceutically acceptable salt thereof is Pyridoxine hydrochloride; and
(c) the riboflavin compound is riboflavin.
22. The method of claim 2 , wherein said dosage form comprises:
(I)
(A) a core consisting of:
(a) about 10 mg of Doxylamine or a pharmaceutically acceptable salt thereof;
(b) about 10 mg of Pyridoxine or a pharmaceutically acceptable salt thereof;
(c) about 40 mg of a riboflavin compound selected from riboflavin, riboflavin-5-phosphate and flavin adenine dinucleotide, or a pharmaceutically acceptable salt thereof; and
(d) one or more pharmaceutically acceptable excipients;
(B) a delayed release coating surrounding said core;
(C) an immediate release component surrounding said delayed release coating and consisting of:
(a) about 10 mg of Doxylamine or a pharmaceutically acceptable salt thereof;
(b) about 10 mg of Pyridoxine or a pharmaceutically acceptable salt thereof; and
(c) one or more pharmaceutically acceptable excipients and/or coatings.
23. The method of claim 2 , wherein said dosage form comprises:
(II)
(A) a core consisting of the following ingredients:
(a) about 10 mg of Doxylamine or a pharmaceutically acceptable salt thereof;
(b) about 10 mg of Pyridoxine or a pharmaceutically acceptable salt thereof; and
(c) one or more pharmaceutically acceptable excipients;
(B) a delayed release coating surrounding said core;
(C) an immediate release component surrounding said delayed release coating and consisting of:
(a) about 10 mg of Doxylamine or a pharmaceutically acceptable salt thereof;
(b) about 10 mg of Pyridoxine or a pharmaceutically acceptable salt thereof;
(c) about 40 mg of a riboflavin compound selected from riboflavin, riboflavin-5-phosphate and flavin adenine dinucleotide, or a pharmaceutically acceptable salt thereof; and
(d) one or more pharmaceutically acceptable excipients and/or coatings.
24. The method of claim 2 , wherein a coating surrounds said delayed release coating.