Controlled release pharmaceutical formulations of nitazoxanide
View Patent ↗Solid dosage formulations of nitazoxanide or a nitazoxanide analogue are provided that comprise a controlled release portion and an immediate release portion. The pharmaceutical composition is typically in the form of a bilayer solid oral dosage form comprising (a) a first layer comprising a first quantity of nitazoxanide or analogue thereof in a controlled release formulation; and (b) a second layer comprising a second quantity of nitazoxanide or analogue thereof in an immediate release formulation. Method of using the formulations in the treatment of hepatitis C are also provided.
1. A pharmaceutical composition in the form of a solid dosage form comprising:
a) controlled release granules comprising a first quantity of nitazoxanide or an analogue thereof and b) immediate release granules comprising a second quantity of nitazoxanide or an analogue thereof.
2. The composition of claim 1 , wherein the solid dosage form is a capsule.
3. The composition of claim 1 , wherein a ratio of the first quantity of nitazoxanide or an analogue thereof to the second quantity of nitazoxanide or an analogue thereof is about 1:1 to about 4:1.
4. The composition of claim 3 , wherein the ratio of the first quantity of nitazoxanide or an analogue thereof to the second quantity of nitazoxanide or an analogue thereof is about 2.5:1 to about 4:1.
5. The composition of claim 1 , further comprising a pharmaceutically acceptable additive or excipient.
6. The composition of claim 5 , wherein the additive or excipient is selected from starch, lactose, xylitol, sorbitol, confectioner's sugar, compressible sugar, dextrates, dextrin, dextrose, fructose, lactitol, mannitol, sucrose, talc, microcrystalline cellulose, calcium carbonate, calcium phosphate dibasic or tribasic, dicalcium phosphaste dehydrate, and calcium sulfate.
7. A method of reducing one or more side-effects associated with treatment with nitazoxanide or tizoxanide in a patient, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition in the form of a solid dosage form, the composition comprising a) controlled release granules comprising a first quantity of nitazoxanide or an analogue thereof and b) immediate release granules comprising a second quantity of nitazoxanide or an analogue thereof.
8. The method of claim 7 , wherein the one or more side effects is selected from abdominal pain, diarrhea, flatulence and nausea.
9. The method of claim 7 , wherein the solid dosage form is a capsule.
10. The method of claim 7 , wherein a ratio of the first quantity of nitazoxanide or an analogue thereof to the second quantity of nitazoxanide or an analogue thereof is about 1:1 to about 4:1.
11. The method of claim 10 , wherein the ratio of the first quantity of nitazoxanide or an analogue thereof to the second quantity of nitazoxanide or an analogue thereof is about 2.5:1 to about 4:1.
12. The method of claim 7 , further comprising a pharmaceutically acceptable additive or excipient.
13. The method of claim 12 , wherein the additive or excipient is selected from starch, lactose, xylitol, sorbitol, confectioner's sugar, compressible sugar, dextrates, dextrin, dextrose, fructose, lactitol, mannitol, sucrose, talc, microcrystalline cellulose, calcium carbonate, calcium phosphate dibasic or tribasic, dicalcium phosphaste dehydrate, and calcium sulfate.
14. A method for increasing the bioavailability of nitazoxanide or an analogue thereof in a patient, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition in the form of a solid dosage form, the composition comprising a) controlled release granules comprising a first quantity of nitazoxanide or an analogue thereof and b) immediate release granules comprising a second quantity of nitazoxanide or an analogue thereof.
15. The method of claim 14 , wherein the solid dosage form is a capsule.
16. The method of claim 14 , wherein a ratio of the first quantity of nitazoxanide or an analogue thereof to the second quantity of nitazoxanide or an analogue thereof is about 1:1 to about 4:1.
17. The method of claim 16 , wherein the ratio of the first quantity of nitazoxanide or an analogue thereof to the second quantity of nitazoxanide or an analogue thereof is about 2.5:1 to about 4:1.
18. The method of claim 14 , further comprising a pharmaceutically acceptable additive or excipient.
19. The method of claim 18 , wherein the additive or excipient is selected from starch, lactose, xylitol, sorbitol, confectioner's sugar, compressible sugar, dextrates, dextrin, dextrose, fructose, lactitol, mannitol, sucrose, talc, microcrystalline cellulose, calcium carbonate, calcium phosphate dibasic or tribasic, dicalcium phosphaste dehydrate, and calcium sulfate.
20. A method of extending absorption of nitazoxanide or an analogue thereof in a patient, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition in the form of a solid dosage form, the composition comprising a) controlled release granules comprising a first quantity of nitazoxanide or an analogue thereof and b) immediate release granules comprising a second quantity of nitazoxanide or an analogue thereof.
21. The method of claim 20 , wherein the solid dosage form is a capsule.
22. The method of claim 20 , wherein a ratio of the first quantity of nitazoxanide or an analogue thereof to the second quantity of nitazoxanide or an analogue thereof is about 1:1 to about 4:1.
23. The method of claim 22 , wherein the ratio of the first quantity of nitazoxanide or an analogue thereof to the second quantity of nitazoxanide or an analogue thereof is about 2.5:1 to about 4:1.
24. The method of claim 20 , further comprising a pharmaceutically acceptable additive or excipient.
25. The method of claim 24 , wherein the additive or excipient is selected from starch, lactose, xylitol, sorbitol, confectioner's sugar, compressible sugar, dextrates, dextrin, dextrose, fructose, lactitol, mannitol, sucrose, talc, microcrystalline cellulose, calcium carbonate, calcium phosphate dibasic or tribasic, dicalcium phosphaste dehydrate, and calcium sulfate.