COMPOSITIONS AND METHODS FOR TREATING NOCTURNAL ACID BREAKTHROUGH AND OTHER ACID RELATED DISORDERS

1 . A method for treating and/or preventing nocturnal acid breakthrough in a subject in need thereof, the method comprising: administering to the subject a solid pharmaceutical composition comprising an acid labile proton pump inhibitor and a buffering agent, wherein:

(a) the proton pump inhibitor is not enteric coated;

(b) the proton pump inhibitor is present in the composition in an amount of about 5 mg to about 60 mg;

(c) the buffering agent is present in the composition in an amount of about 200 mg to about 3500 mg; and

(d) the administration step is performed between about 8:00 pm and about 12:00 am, inclusive.

2 . The method of claim 1 , wherein the administration step is performed between about 9:00 pm and about 12:00 am, inclusive.

3 . The method of claim 1 , wherein the administration step is performed between about 9:30 pm and about 11:30 pm, inclusive.

4 . The method of claim 1 wherein the proton pump inhibitor is of Formula (I):

wherein

R 1 is hydrogen, alkyl, halogen, cyano, carboxy, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoylalkyl, hydroxy, alkoxy which is optionally fluorinated, hydroxyalkyl, trifluoromethyl, acyl, carbamoyloxy, nitro, acyloxy, aryl, aryloxy, alkylthio, or alkylsulfinyl;

R 2 is hydrogen, alkyl, acyl, acyloxy, alkoxy, amino, aralkyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonylmethyl, alkoxycarbonylmethyl, or alkylsulfonyl;

R 3 and R 5 are the same or different and each is hydrogen, alkyl, alkoxy, amino, or alkoxyalkoxy;

R 4 is hydrogen, alkyl, alkoxy which may optionally be fluorinated, or alkoxyalkoxy;

Q is nitrogen, CH, or CR 1 ;

W is nitrogen, CH, or CR 1 ;

y is an integer of 0 through 4; and

Z is nitrogen, CH, or CR 1 ;

or a free base, salt, ester, hydrate, amide, enantiomer, isomer, tautomer, prodrug, polymorph, or derivative thereof.

5 . The method of claim 1 wherein the proton pump inhibitor is omeprazole, tenatoprazole, lansoprazole, rabeprazole, esomeprazole, pantoprazole, pariprazole, leminoprazole and nepaprazole or a free base, a free acid, or a salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, prodrug, or derivative of such compounds.

6 . The method of claim 1 wherein the proton pump inhibitor is omeprazole or lansoprazole.

7 . The method of claim 1 wherein the proton pump inhibitor is omeprazole.

8 . The method of claim 1 wherein the proton pump inhibitor is present in an amount of about 10 mg to about 40 mg on a dry weight basis.

9 . The method of claim 1 wherein the buffering agent is present in an amount of about 400 mg to about 3000 mg on a dry weight basis.

10 . The method of claim 1 wherein the buffering agent is present in an amount of about 500 mg to about 2500 mg on a dry weight basis.

11 . The method of claim 1 wherein the composition further comprises at least one pharmaceutically acceptable excipient.

12 . The method of claim 1 wherein the composition is a dosage form is selected from a tablet, a suspension tablet, a bite suspension tablet, a rapid dispersion tablet, a chewable tablet, an effervescent tablet, a bilayer tablet, a caplet, a capsule, a powder, a lozenge, a sachet, a cachet, a troche, a pellet, a granule and a microgranule.

13 . A method for treating and/or preventing nocturnal acid breakthrough in a subject in need thereof, the method comprising: administering to the subject a solid pharmaceutical composition comprising an acid labile proton pump inhibitor and a buffering agent, wherein:

(a) the proton pump inhibitor is not enteric coated,

(b) the proton pump inhibitor is present in the composition in an amount of about 5 mg to about 60 mg;

(c) the buffering agent is present in the composition in an amount of about 200 mg to about 3500 mg; and

(d) the administration step is performed prior to 12:00 am and at such a time so as to result in a blood serum concentration of the proton pump inhibitor of at least about 0.1 micromolar at any time point from about 12:00 am to about 6:00 am following administration.

14 . The method of claim 13 wherein the administration step is performed at such a time so as to result in a blood serum concentration of the proton pump inhibitor of at least about 0.9 micromolar at any time point from about 1:00 am to about 5:00 am following administration.

15 . The method of claim 13 wherein the proton pump inhibitor is of Formula (I):

wherein

R 1 is hydrogen, alkyl, halogen, cyano, carboxy, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoylalkyl, hydroxy, alkoxy which is optionally fluorinated, hydroxyalkyl, trifluoromethyl, acyl, carbamoyloxy, nitro, acyloxy, aryl, aryloxy, alkylthio, or alkylsulfinyl;

R 2 is hydrogen, alkyl, acyl, acyloxy, alkoxy, amino, aralkyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonylmethyl, alkoxycarbonylmethyl, or alkylsulfonyl;

R 3 and R 5 are the same or different and each is hydrogen, alkyl, alkoxy, amino, or alkoxyalkoxy;

R 4 is hydrogen, alkyl, alkoxy which may optionally be fluorinated, or alkoxyalkoxy;

Q is nitrogen, CH, or CR 1 ;

W is nitrogen, CH, or CR 1 ;

y is an integer of 0 through 4; and

Z is nitrogen, CH, or CR 1 ;

or a free base, salt, ester, hydrate, amide, enantiomer, isomer, tautomer, prodrug, polymorph, or derivative thereof.

16 . The method of claim 13 wherein the proton pump inhibitor is omeprazole, tenatoprazole, lansoprazole, rabeprazole, esomeprazole, pantoprazole, pariprazole, leminoprazole and nepaprazole or a free base, a free acid, or a salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, prodrug, or derivative of such compounds.

17 . The method of claim 13 wherein the proton pump inhibitor is omeprazole or lansoprazole.

18 . The method of claim 13 wherein the proton pump inhibitor is omeprazole.

19 . The method of claim 13 wherein the proton pump inhibitor is present in an amount of about 10 mg to about 40 mg on a dry weight basis.

20 . The method of claim 13 wherein the buffering agent is present in an amount of about 400 mg to about 3000 mg on a dry weight basis.

21 . The method of claim 13 wherein the buffering agent is present in an amount of about 500 mg to about 2500 mg on a dry weight basis.

22 . The method of claim 13 wherein the composition further comprises at least one pharmaceutically acceptable excipient.

23 . The method of claim 13 wherein the composition is a solid dosage form is selected from a tablet, a suspension tablet, a bite suspension tablet, a rapid dispersion tablet, a chewable tablet, an effervescent tablet, a bilayer tablet, a caplet, a capsule, a powder, a lozenge, a sachet, a cachet, a troche, a pellet, a granule and a microgranule.

24 . A method for treating and/or preventing nocturnal acid breakthrough in a subject in need thereof, the method comprising: administering to the subject a solid pharmaceutical composition comprising an acid labile proton pump inhibitor and a buffering agent, wherein:

(a) the proton pump inhibitor is not enteric coated;

(b) the proton pump inhibitor is present in the composition in an amount of about 5 mg to about 60 mg;

(c) the buffering agent is present in the composition in an amount of about 200 mg to about 3500 mg; and

(d) the administration step is performed prior to 2:00 am and at such a time so as to result in a blood serum concentration of the proton pump inhibitor of at least about 1 micromolar at any time point from about 2:00 am to about 4:00 am following administration.

25 . A method for treating and/or preventing nocturnal acid breakthrough in a subject in need thereof, the method comprising the steps of:

(a) determining the subject's typical period of nocturnal acid breakthrough; and

(b) providing the subject with a pharmaceutical composition comprising an acid labile, substituted benzimidazole H + , K + -ATPase proton pump inhibitor and a buffering agent at a time such that the subject exhibits a blood serum concentration of the proton pump inhibitor of at least about 0.1 micromolar at any time point during the subject's determined typical period of nocturnal acid breakthrough.

26 . A method for treating and/or preventing nocturnal acid breakthrough in a subject in need thereof, the method comprising the steps of:

(a) determining the subject's typical period of nocturnal acid breakthrough; and

(b) providing the subject with a pharmaceutical composition comprising an acid labile, substituted benzimidazole H + , K + -ATPase proton pump inhibitor and a buffering agent at a time such that the subject exhibits a blood serum concentration of the proton pump inhibitor of at least about 1 micromolar at any time point during the subject's determined typical period of nocturnal acid breakthrough.