Controlled-release formulations, method of manufacture, and use thereof

1. A controlled-release matrix composition in a solid dosage form, consisting essentially of:

a pharmaceutically effective amount of an active agent, or a pharmaceutically acceptable salt or solvate thereof;

an ionic non-gelling matrix polymer that is practically insoluble and unswellable at a first aqueous fluid pH and is soluble at a second aqueous fluid pH, wherein the ionic non-gelling matrix polymer is selected from the group consisting of cellulose acetate phthalate, cellulose acetate succinate, polyvinylacetate phthalate, cellulose acetate maleate, cellulose acetate trimellitate, cellulose acetate butyrate, cellulose acetate propionate, a methacrylic acid-methyl methacrylate co-polymer, a methacrylic acid-ethyl acrylate co-polymer, a methacrylic acid-methyl acrylate-methyl methacrylate, and a combination thereof;

a pH modifier present in an amount to control the release of the active agent from the composition, wherein the pH modifier is a pharmaceutically acceptable organic acid, or an alkali metal or alkaline earth metal salt thereof; and

a soluble, non-gelling pharmaceutically acceptable excipient;

wherein the controlled-release matrix composition is substantially free of a gelling or swelling excipient and does not contain a functional coating or a lipophilic component.

2. The controlled-release composition of claim 1 , wherein the ionic non-gelling matrix polymer is selected from the group consisting of a methacrylic acid-methyl methacrylate co-polymer, a methacrylic acid-ethyl acrylate co-polymer, methacrylic acid-methyl acrylate-methyl methacrylate, and a combination thereof.

3. The controlled-release composition of claim 1 , wherein the ionic non-gelling matrix polymer is present in an amount from about 5 to about 85 wt % based on the total weight of the composition.

4. The controlled-release composition of claim 1 , wherein the active agent is selected from the group consisting of an antihypertensive agent, an antidepressant agent, an antianxiety agent, an anticlotting agent, an anticonvulsant agent, a blood glucose-lowering agent, a decongestant agent, an antihistamine agent, an antitussive agent, an anti-inflammatory agent, an antipsychotic agent, a cognitive enhancer, a cholesterol-reducing agent, an antiobesity agent, an autoimmune disorder agent, an anti-impotence agent, an antibacterial agent, an antifungal agent, a hypnotic agent, an anti-Parkinsonism agent, an antiviral agent, an anti-neoplastic agent, a barbituate agent, a sedative agent, a nutritional agent, a beta blocker, an emetic agent, an anti-emetic agent, a diuretic agent, an anticoagulant agent, a cardiotonic agent, an androgen agent, a corticoid, an anabolic agent, a growth hormone secretagogue, an anti-infective agent, a coronary vasodilator, a carbonic anhydrase inhibitor, an antiprotozoal agent, a gastrointestinal agent, a serotonin antagonist, an anesthetic agent, a hypoglycemic agent, a dopaminergic agent, an anti-Alzheimer's Disease agent, an anti-ulcer agent, a platelet inhibitor, a glycogen phosphorylase inhibitor, a muscle relaxant, and a pharmaceutically acceptable combination thereof.

5. The controlled-release composition of claim 1 , wherein the active agent has a solubility of greater than or equal to about 2.0 mg/ml in an aqueous medium at room temperature.

6. The controlled-release composition of claim 5 , wherein the active agent is quetiapine or a salt thereof.

7. The controlled-release composition of claim 1 , wherein the pH modifier is sodium citrate.

8. The controlled-release composition of claim 1 , wherein the pH modifier is present in the matrix in an amount from about 2 to about 50 wt % based on the total weight of the composition.

9. The controlled-release composition of claim 1 , wherein the soluble, non-gelling pharmaceutically acceptable excipient is a sugar polyol, a monosaccharide, a disaccharide, a polysaccharide, or a combination thereof.

10. The controlled-release composition of claim 1 , wherein the soluble, non-gelling pharmaceutically acceptable excipient is lactose, sucrose, dextrose, fructose, glucose, maltose, polydexotrose, sorbitol, xylitoi, mannitol, galactitol, maltitol, lactitol, erythritol, maltose, dextrin, maltodextrin, xylose, galactose, trehalose, tagatose, or a combination thereof.

11. The controlled-release composition of claim 1 , wherein the soluble, non-gelling pharmaceutically acceptable excipient is present in an amount from about 1 to about 70 wt % based on the total weight of the composition.

12. The controlled-release composition of claim 1 , wherein the first aqueous fluid has a pH equal to or less than about 4.5, and the second aqueous fluid has a pH greater than about 4.5.

13. The controlled-release composition of claim 1 , wherein the first aqueous fluid is human gastric fluid, and the second aqueous fluid is human intestinal fluid.

14. The controlled-release composition of claim 1 , wherein the solid dosage form is a tablet, a capsule, a granule, a mini-tablet, or a pellet.

15. The controlled-release composition of claim 1 , wherein the controlled-release composition is in a once a day dosage form or a twice a day dosage form.

16. A controlled-release matrix composition in a solid dosage form, consisting essentially of:

a pharmaceutically effective amount of an active agent, or a pharmaceutically acceptable salt or solvate thereof;

an ionic non-gelling matrix polymer that is practically insoluble and unswellable at a first aqueous fluid pH and is soluble at a second aqueous fluid pH, wherein the ionic non-gelling matrix polymer is selected from the group consisting of cellulose acetate phthalate, cellulose acetate succinate, polyvinylacetate phthalate, cellulose acetate maleate, cellulose acetate trimellitate, cellulose acetate butyrate, cellulose acetate propionate, a methacrylic acid-methyl methacrylate co-polymer, a methacrylic acid-ethyl acrylate co-polymer, a methacrylic acid-methyl acrylate-methyl methacrylate, and a combination thereof;

a pH modifier present in an amount to control the release of the active agent from the composition, wherein the pH modifier is a pharmaceutically acceptable organic acid, or an alkali metal or alkaline earth metal salt thereof;

a soluble, non-gelling pharmaceutically acceptable excipient; and

a non-functional coating;

wherein the controlled-release matrix composition is substantially free of a gelling or swelling excipient and does not contain a functional coating or a lipophilic component.