Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
View Patent ↗In one general aspect of the present invention, pharmaceutical formulations comprising both a proton pump inhibitor microencapsulated or dry coated with a material that enhances the shelf-life of the pharmaceutical composition and one or more antacid are described. In another general aspect of the present invention, pharmaceutical formulations comprising both a proton pump inhibitor microencapsulated or dry coated with a taste-masking material and one or more antacid are described.
1. A solid pharmaceutical composition having an enhanced shelf-life, comprising:
(a) about 1 to about 120 mg of omeprazole, or a free base, free acid, salt, enantiomer, isomer, or tautomer, thereof, in combination with sodium bicarbonate, wherein said combination is microencapsulated with a material that enhances the shelf-life of the pharmaceutical composition comprising at least one cellulose hydroxypropyl ether; and
(b) about 1 to about 160 mEq of antacid comprising sodium bicarbonate wherein the pharmaceutical composition is not enteric coated and has less than 5% total new impurities after 1 year of storage at room temperature.
2. The pharmaceutical composition according to claim 1 , wherein the antacid comprises at least one soluble buffer.
3. The pharmaceutical composition according to claim 2 , wherein the soluble buffer is present in about 5 mEq to about 40 mEq.
4. The pharmaceutical composition according to claim 1 comprising about 500 to about 2000 mg of antacid.
5. The pharmaceutical composition according to claim 1 , wherein the omeprazole has less than 1% degradation after one month of storage at room temperature.
6. The pharmaceutical composition according to claim 1 further comprising one or more excipients selected from the group consisting of parietal cell activators, organic solvents, erosion facilitators, flavoring agents, sweetening agents, diffusion facilitators, antioxidants and carrier materials selected from binders, suspending agents, disintegration agents, filling agents, surfactants, solubilizers, stabilizers, lubricants, wetting agents, diluents, anti-adherents, and antifoaming agents.
7. The pharmaceutical composition according to claim 6 , wherein the flavoring agent comprises peach, menthol, aspartame, sucralose, xylitol, mint, sucrose, or a mixture thereof.
8. The pharmaceutical composition according to claim 1 in the form of a capsule, a chewable tablet, a tablet, or a powder.
9. The pharmaceutical composition according to claim 1 , wherein the maximum serum concentration is reached within about 1 hour after administration of the pharmaceutical formulation to a subject.
10. The pharmaceutical composition according the claim 1 , wherein the average particle size of the microencapsulated omeprazole is between about 20 to about 500 microns in diameter.
11. The pharmaceutical composition according the claim 1 , wherein the average particle size of the microencapsulated proton pump inhibitor is between about 50 to about 150 microns in diameter.
12. A method of treating an acid related gastrointestinal disorder in a subject in need thereof by administering a pharmaceutical composition having an enhanced shelf-life, comprising:
(a) about 1 to about 120 mg of omeprazole or a free base, free acid, salt, enantiomer, isomer, or tautomer thereof in combination with sodium bicarbonate, wherein said combination is microencapsulated with a material that enhances the shelf-life of the pharmaceutical composition wherein the material that enhances the shelf-life of the pharmaceutical formulation comprising at least one cellulose hydroxypropyl ether; and
(b) about 1 to about 160 mEq of at least one antacid comprising sodium bicarbonate; wherein the pharmaceutical composition is not enteric coated and has less than 5% total new impurities after 1 year of storage at room temperature.
13. The pharmaceutical composition according to claim 1 , wherein a serum concentration of the omeprazole is about 0.3 μg/ml within about 45 minutes after administration of the pharmaceutical formulation to a subject.
14. The pharmaceutical composition according to claim 1 , wherein a serum concentration of the omeprazole is about 0.45μg/ml within about 30 minutes after administration of the pharmaceutical formulation to a subject.
15. The pharmaceutical composition according to claim 1 , wherein a serum concentration of the omeprazole is about 0.1 μg/ml within about 15 minutes after administration of the pharmaceutical formulation to a subject.
16. The pharmaceutical composition according to claim 1 , wherein about 50% of the omeprazole is released from the composition within about 1 hour after exposure to gastrointestinal fluid.
17. The pharmaceutical composition according to claim 1 , wherein about 70% of the omeprazole is released from the composition within about 1.5 hours after exposure to gastrointestinal fluid.
18. The pharmaceutical composition according to claim 1 , wherein a maximum serum concentration is reached within about 45 minutes after administration of the pharmaceutical formulation to a fasting subject.
19. The pharmaceutical composition according to claim 1 , wherein the antacid is present in an amount of about 1 mEq to about 3 mEq per mg of omeprazole.
20. The pharmaceutical composition according to claim 1 , wherein the antacid is present in an amount of between about 5 mEq to about 60 mEq.
21. The pharmaceutical composition according to claim 1 , wherein the material that enhances the shelf-life of the pharmaceutical formulation sufficiently dissolves in water in less than about 30 minutes.
22. The pharmaceutical composition according to claim 1 , wherein the material that enhances the shelf-life of the pharmaceutical formulation sufficiently disintegrates to release the omeprazole into the gastrointestinal fluid within about 1 hour.
23. The pharmaceutical composition according to claim 1 , wherein the drug loading of the omeprazole into microspheres is about 20 wt-% of omeprazole to microencapsulated omeprazole.
24. The pharmaceutical composition according to claim 1 , wherein the drug loading of the omeprazole into microspheres is between about 10 wt-% to about 60 wt-% of omeprazole to microencapsulated omeprazole.
25. A chewable tablet, comprising:
(a) between about 1 to about 120 mg of omeprazole, or a free base, free acid, salt, enantiomer, isomer, or tautomer thereof in combination with sodium bicarbonate, wherein said combination is microencapsulated with a material that enhances the shelf-life of the chewable tablet comprising cellulose hydroxypropyl ether;
(b) between about 1 mEq and about 160 mEq of antacid comprising sodium bicarbonate; and
(c) at least one flavoring agent; wherein the pharmaceutical composition is not enteric coated and has less than 5% total new impurities after 1 year of storage at room temperature;
wherein upon administration of the chewable tablet to a fasted subject, the maximum serum concentration of the omeprazole is reached within about 45 minutes after administration.
26. The chewable tablet according to claim 25 , wherein the flavoring agent comprises peach, menthol, aspartame, sucralose, sucrose, xylitol, mint, or a mixture thereof.
27. The chewable tablet according to claim 25 , wherein a serum concentration of the omeprazole is about 0.5 μg/ml within about 1 hour after administration of the pharmaceutical formulation to a subject.
28. The chewable tablet according to claim 25 , wherein about 70% of the omeprazole is released from the composition within about 1.5 hours after exposure to gastrointestinal fluid.
29. The chewable tablet according to claim 25 , wherein the antacid is present in an amount of about 1.0 mEq to about 3 mEq per mg of omeprazole.
30. The chewable tablet according to claim 25 , wherein the antacid comprises sodium bicarbonate, sodium carbonate, calcium carbonate, magnesium oxide, potassium bicarbonate, magnesium hydroxide, magnesium, carbonate, and mixtures thereof.
31. The chewable tablet according to claim 25 , wherein the drug loading of the proton pump inhibitor into microspheres is about 20 wt-% of omeprazole to microencapsulated omeprazole.
32. The chewable tablet according to claim 25 , wherein the drug loading of the omeprazole into microspheres is between about 10 wt-% to about 60 wt-% of omeprazole to microencapsulated omeprazole.