Formulation of doxylamine and pyridoxine and/or metabolites or salts thereof
View Patent ↗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).
1. A method for alleviating the symptoms of nausea and vomiting, said method comprising administering to a human subject in need thereof 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 dosage form comprises from about 10 mg to about 30 mg of doxylamine and/or pharmaceutically acceptable salt thereof and from about 10 mg to about 30 mg of pyridoxine and/or pharmaceutically acceptable salt thereof, and
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 composition, within the gastrointestinal tract.
2. The method of claim 1 , wherein said human subject is a pregnant woman and said nausea and vomiting is nausea and vomiting of pregnancy (NVP).
3. The method of claim 1 , wherein said dosage form comprises from about 10 mg to about 20 mg of doxylamine and/or pharmaceutically acceptable salt thereof.
4. The method of claim 3 , wherein said dosage form comprises about 20 mg of doxylamine and/or pharmaceutically acceptable salt thereof.
5. The method of claim 1 , wherein said dosage form comprises from about 10 mg to about 20 mg of pyridoxine and/or pharmaceutically acceptable salt thereof.
6. The method of claim 5 , wherein said dosage form comprises about 20 mg of pyridoxine and/or pharmaceutically acceptable salt thereof.
7. The method of claim 1 , wherein said immediate release composition comprises doxylamine succinate.
8. The method of claim 1 , wherein said delayed release composition comprises doxylamine succinate.
9. The method of claim 1 , wherein said immediate release composition comprises pyridoxine hydrochloride.
10. The method of claim 1 , wherein said delayed release composition comprises pyridoxine hydrochloride.
11. The method of claim 1 , wherein said dosage form comprises:
(a) a core comprising said delayed release composition;
(b) a delayed release coating substantially surrounding the core; and
(c) one or more coats substantially surrounding said delayed release coating, said one or more coats comprising said immediate release composition.
12. The method of claim 11 , wherein the one or more coats comprise a first coat and a second coat.
13. The method of claim 12 , wherein the first coat comprises the doxylamine and/or pharmaceutically acceptable salt thereof, and the second coat comprises the pyridoxine and/or a pharmaceutically acceptable salt thereof.
14. The method of claim 11 , wherein:
(A) said core comprises:
(a) about 5 to about 15 mg of doxylamine succinate; and
(b) about 5 to about 15 mg of pyridoxine hydrochloride;
(B) said delayed release coating is an enteric coating; and
(C) said one or more coats comprise:
(a) about 5 to about 15 mg of doxylamine succinate; and
(b) about 5 to about 15 mg of pyridoxine hydrochloride.
15. The method of claim 11 , wherein:
(i) said core comprises:
(a) about 10 mg of doxylamine succinate; and
(b) about 10 mg of pyridoxine hydrochloride; and
(ii) said one or more coats comprise:
(a) a first coat comprising about 10 mg of pyridoxine hydrochloride; and
(b) a second coat comprising about 10 mg of doxylamine succinate.
16. The method of claim 1 , wherein said dosage form is administered under fasted conditions.
17. The method of claim 1 , wherein said dosage form is administered under fed conditions.
18. The method of claim 1 , wherein said dosage form is administered from once-a-day to three times a day.
19. The method of claim 18 , wherein said dosage form is administered twice-a-day.
20. The method of claim 15 , wherein said dosage form is administered from once-a-day to three times a day.
21. The method of claim 20 , wherein said dosage form is administered twice-a-day.