Novel formulations of proton pump inhibitors and methods of using these formulations

A method of treating a gastrointestinal disorder in a patient comprising the step of administering a composition in a solid dosage form comprising:

• (a) about 10 mgs to about 100 mgs of at least one acid labile bicyclic-aryl-imidazole proton pump inhibiting agent;
• (b) at least one antacid in an amount sufficient to increase gastric fluid pH to a pH that prevents acid degradation of at least some of the proton pump inhibitor in the gastric fluid;
• wherein the antacid comprises at least about 400 mgs of NaHCO3;
• and
• (c) about 0.5 wt-% to about 3 wt-% of sodium stearyl fumarate;
• wherein the composition is administered to a fasted subject daily and the Tmax of the proton pump inhibitor is less than about 45 minutes on Day 1 and Day 7 of administration of the composition.

A method of treating or preventing nocturnal acid breakthrough or reducing nighttime gastric acidity in a patient by administering a pharmaceutical composition in solid dosage form at bedtime, wherein the pharmaceutical composition comprises:

• (a) about 10 mgs to about 100 mgs of at least one acid labile bicyclic-aryl-imidazole proton pump inhibiting agent;
• (b) at least one antacid in an amount sufficient to increase gastric fluid pH to a pH that prevents acid degradation of at least some of the proton pump inhibitor in the gastric fluid;
• wherein the antacid comprises at least about 400 mgs of NaHCO3;
• and
• (c) about 0.5 wt-% to about 3 wt-% of sodium stearyl fumarate;
• wherein the composition is administered to a fasted subject daily and the Tmax of the proton pump inhibitor is less than about 45 minutes on Day 1 and Day 7 of administration.

A method of treating or preventing nocturnal acid breakthrough or reducing nighttime gastric acidity in a patient by administering a pharmaceutical composition in solid dosage form at bedtime, wherein the pharmaceutical composition comprises:

• (a) about 10 to about 100 mgs of at least one acid labile bicyclic-aryl-imidazole proton pump inhibiting agent;
• and
• (b) between about 20 mEq to about 40 mEq of antacid, wherein the antacid comprises at least about 400 mgs of NaHCO3;
• wherein after administration of the composition for 7 days, the composition is at least about 20% better at maintaining the pH of the patients stomach above 4 during the first 4 hours after administration.

A pharmaceutical composition in a tablet dosage form comprising:

• (a) about 20 to about 100 mg of a proton pump inhibitor;
• and
• (b) at least about 400 mgs of directly compressible sodium bicarbonate;
• wherein the hardness of the tablet is between 10-20 kP.

A pharmaceutical composition in a tablet dosage form comprising:

• (a) about 20 mg to about 80 mg of a proton pump inhibitor selected from omeprazole and esomeprazole, or a pharmaceutically acceptable salt, solvate or polymorph thereof;
• (b) about 400 mgs to about 1,400 mgs of directly compressible sodium bicarbonate;
• (c) about 2 wt-% to about 8 wt-% of a disintegrant;
• (d) about 3 wt-% to about 10 wt-% of a binder;
• and
• (e) about 0.5 wt-% and about 3 wt-% of a lubricant.

A pharmaceutical composition comprising:

• an immediate release portion of the composition comprising:
• (a) about 20 mgs to about 100 mgs of at least one acid labile bicyclic-aryl-imidazole proton pump inhibiting agent;
• (b) at least one antacid in an amount sufficient to increase gastric fluid pH to a pH that prevents acid degradation of at least some of the proton pump inhibitor in the gastric fluid;
• wherein the antacid comprises at least about 400 mgs of directly compressible NaHCO3;
• and
• a sustained release portion of the composition comprising:
• (a) about 20 mgs to about 100 mgs of at least one acid labile bicyclic-aryl-imidazole proton pump inhibiting agent;
• and
• (b) about 10-80 wt-% of at least one slowly soluble polymer or a combination of slowly soluble polymers;
• wherein upon administration to a subject, a measurable serum level of the PPI is achieved for more than about 4 hours.

A pharmaceutical composition comprising:

• an immediate release portion of the composition comprising:
• (a) about 20 mgs to about 100 mgs of at least one acid labile bicyclic-aryl-imidazole proton pump inhibiting agent;
• (b) at least one antacid in an amount sufficient to increase gastric fluid pH to a pH that prevents acid degradation of at least some of the proton pump inhibitor in the gastric fluid;
• wherein the antacid comprises at least about 400 mgs of directly compressible NaHCO3;
• and
• a sustained release portion of the composition comprising:
• (a) about 20 mgs to about 100 mgs of at least one acid labile bicyclic-aryl-imidazole proton pump inhibiting agent;
• and
• (b) about 10-80 wt-% of at least one slowly soluble polymer or a combination of slowly soluble polymers;
• wherein at least about 70% of the proton pump inhibitor in the immediate release portion of the composition is released within about 1 hour and less than about 80% of the proton pump inhibitor in the sustained release portion of the composition is released within 2 hours in vitro.