Pharmaceutical composition with gastric residence and controlled release

1. A controlled-release pharmaceutical composition with gastric residence comprising two or three layers and consisting essentially of:

(a) an active principle combined with an excipient which modifies its release,

(b) a carbon dioxide-generating system in a swelling hydrophilic polymer matrix consisting of a hydrophilic polymer chosen from the following families of hydrophilic polymers:

natural polysaccharides,

cellulose derivatives,

polyvinylpyrrolidones,

polymers derived from acrylic acid and methacrylic acid and salts thereof, or

aminoacid polymers,

or a mixture of 2 or 3 hyrdophilic polymers chosen from the same family wherein (a) and (b) are included in the same layer [(a)+(b)] or in separate layers ](a)[ and [(b)] and wherein multiple layers containing (a), (b) or (a) and (b) in the same tablet have the same or different compositions and dimensions, and

(c) a hydrophilic excipient capable of promoting the hydration of swelling polymer matrices, chosen from lactose, mannitol, sorbitol, microcrystalline cellulose, sodium lauryl sulfate, sodium ricinoleate, sodium tetradecyl sulfate, sodium dioctyl sulfosulfonate, ketomagrocol, poloxamer and polysorbates.

2. A composition according to claim 1 wherein the carbon dioxide-generating system comprises at least one carbon dioxide-generating agent chosen from an alkali metal carbonate, an alkaline-earth metal carbonate and an alkali metal bicarbonate.

3. A composition according to claim 2 wherein the carbon dioxide-generating system comprises at least one carbon dioxide-generating agent and at least one acidic compound chosen from the group consisting of monocarboxylic acids, polycarboxylic acids and partial salts of polycarboxylic acids.

4. A composition according to claim 3 wherein the acidic compound is tartaric acid, succinic acid, citric acid or a partial salt thereof.

5. A composition according to claim 4 wherein the active principle is a benzamide.

6. A composition according to claim 4 wherein the active principle is an α 1 -antagonist.

7. A composition according to claim 4 wherein the active principle is captopril, furosemide, ursodeoxycholic acid, amoxicillin, (+)-α-aminomethyl-2-methoxy-5-sulfonamidobenzenemethanol or 3′-(2-amino-1-hydroxyethyl)-4′-fluoromethanesulfonanilide, or a salt thereof.

8. A composition according to claim 4 wherein the active principle is selected from the group consisting of amisulpride (D)-tartrate, (S)-(−)-amisulpride, (S)-(−)-amisulpride (D)-tartrate, tiapride hydrochloride, alfuzosine hydrochloride and 3′-(2-amino-1-hydroxyethyl)4′-fluoromethanesulfonanilide hydrochloride.

9. A composition according to claim 1 wherein the active principle is a benzamide.

10. A composition according to claim 1 wherein the active principle is an α 1 -antagonist.

11. A composition according to claim 1 wherein the active principle is captopril, furosemide, ursodeoxycholic acid, amoxicillin, (+)-α-aminomethyl-2-methoxy-5-sulfonamidobenzenemethanol or 3′-(2-amino-1-hydroxyethyl)-4′-fluoromethanesulfonanilide, or a salt thereof.

12. A composition according to claim 1 wherein the active principle is selected from the group consisting of amisulpride (D)-tartrate, (S)-(−)-amisulpride, (S)-(−)-amisulpride (D)-tartrate, tiapride hydrochloride, alfuzosine hydrochloride and 3′-(2-amino-1-hydroxyethyl)4′-fluoromethanesulfonanilide hydrochloride.

13. A composition according to claim 1 wherein the excipient which modifies the release of the active principle is a hydrophilic polymer chosen from the following families of hydrophilic polymers:

natural polysaccharides,

cellulose derivatives,

polyvinylpyrrolidones,

polymers derived from acrylic acid and methacrylic acid and salts thereof, or

aminoacid polymers,

or a mixture of 2 or 3 hydrophilic polymers chosen from the same family,

or, when (a) and (b) are in separate layers, said excipient may further be a lipid substance chosen from hydrogenated castor oil, beeswax, carnauba wax, glyceryl trimyristate, glyceryl trilaurate, glyceryl tristearate, cetyl palmitate and glyceryl behenate, or a combination of a hydrophilic polymer and a lipid substance.

14. A composition according to claim 13 wherein the carbon dioxide-generating system comprises at least one carbon dioxide-generating agent which may be chosen from an alkali metal carbonate or alkaline-earth metal carbonate and an alkali metal bicarbonate.

15. A composition according to claim 14 wherein the carbon dioxide-generating system comprises at least one carbon dioxide-generating agent and at least one acidic compound chosen from the group consisting of monocarboxylic acids, polycarboxylic acids and partial salts of polycarboxylic acids.

16. A composition according to claim 15 wherein the acidic compound is tartaric acid, succinic acid, citric acid or a partial salt thereof.

17. A composition according to claim 16 wherein the active principle is a benzamide.

18. A composition according to claim 16 wherein the active principle is an α 1 -antagonist.

19. A composition according to claim 16 wherein the active principle is captopril, furosemide, ursodeoxycholic acid, amoxicillin, (+)-α-aminomethyl-2-methoxy-5-sulfonamidobenzenemethanol or 3′-(2-amino-1-hydroxyethyl)-4′-fluoromethanesulfonanilide, or a salt thereof.

20. A composition according to claim 16 wherein the active principle is selected from the group consisting of amisulpride (D)-tartrate, (S)-(−)-amisulpride, (S)-(−)-amisulpride (D)-tartrate, tiapride hydrochloride, alfuzosine hydrochloride and 3′-(2-amino-1-hydroxyethyl)-4′-fluoromethanesulfonanilide hydrochloride.

21. A composition according to claim 1 wherein the hydrophilic polymer is chosen from

alginates, xantham gum, guar gum, gum arabic or carob gum,

methylhydroxyethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, calcium carboxymethylcellulose, hydroxypropylcellulose or hydroxypropylmethylcellulose,

polyacrylates, or polylysines.

22. A composition according to claim 21 wherein the excipient which modifies the release of the active principle is a hydrophilic polymer chosen from the following families of hydrophilic polymers:

natural polysaccharides,

cellulose derivatives,

polyvinylpyrrolidones,

polymers derived from acrylic acid and methacrylic acid and salts thereof, or

aminoacid polymers,

or a mixture of 2 or 3 hydrophilic polymers chosen from the same family,

or, when (a) and (b) are in separate layers, said excipient may further be a lipid substance chosen from hydrogenated castor oil, beeswax, carnauba wax, glyceryl trimyristate, glyceryl trilaurate, glyceryl tristearate, cetyl palmitate and glyceryl behenate, or a combination of a hydrophilic polymer and a lipid substance.

23. A composition according to claim 22 wherein the carbon dioxide-generating system comprises at least one carbon dioxide-generating agent chosen from an alkali metal carbonate or alkaline-earth metal carbonate and an alkali metal bicarbonate.

24. A composition according to claim 23 wherein the carbon dioxide-generating system comprises at least one carbon dioxide-generating agent and at least one acidic compound chosen from the group consisting of monocarboxylic acids, polycarboxylic acids and partial salts of polycarboxylic acids.

25. A composition according to claim 24 wherein the acidic compound is tartaric acid, succinic acid, citric acid or a partial salt thereof.

26. A composition according to claim 25 wherein the active principle is a benzamide.

27. A composition according to claim 25 wherein the active principle is an α 1 -antagonist.

28. A composition according to claim 25 wherein the active principle is captopril, furosemide, ursodeoxycholic acid, amoxicillin, (+)-α-aminomethyl-2-methoxy-5-sulfonamidobenzenemethanol or 3′-(2-amino-1-hydroxyethyl)-4′-fluoromethanesulfonanilide, or a salt thereof.

29. A composition according to claim 25 wherein the active principle is selected from the group consisting of amisulpride (D)-tartrate, (S)-(−)-amisulpride, (S)-(−)-amisulpride (D)-tartrate, tiapride hydrochloride, alfuzosine hydrochloride and 3′-(2-amino-1-hydroxyethyl)-4′-fluoromethanesulfonanilide hydrochloride.