Controlled Release Formulations

• US 20080057123A1
• Filed: 08/29/2007
• Published: 03/06/2008
• Est. Priority Date: 08/30/2006
• Status: Abandoned Application

• Current Assignee: Jagotec Ag (Vectura Group Ltd.)
• Original Assignee: Jagotec Ag (Vectura Group Ltd.)
• Inventors: Vergnault, Guy, Grenier, Pascal, Nhamias, Alain
• Application Number:
  US11/847,012
• Publication Number:
  US 20080057123A1
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2886 having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Controlled release oral dosage formulations containing one or more active agent, and methods of use thereof, are provided for the once-a-day treatment. The formulation can be in the form of a trilayer tablet containing a core or central layer and one or more barrier layers. The core may contain one or more enteric materials or polymeric materials which modulates the release of the active agent.

Claims

1. A controlled release solid oral dosage formulation comprising

(a) a core comprising one or more active agents and one or more enteric materials;

and optionally

(b) one or more barrier layers comprising one or more swellable, erodible, or gellable polymers,

wherein, upon administration to a subject, the active agent is released with an ascending release rate in response to the changes in pH as the dosage formulation descends the GI tract.

2. The formulation of claim 1, wherein the one or more active agents is selected from the group consisting of hypnotics, sedatives, tranquilizers, anti-convulsants, musclerelaxants, analgesics, anti-inflammatory, anesthetics, anti-spasmodics, anti-ulcer-agents, anti-parasitics, anti-microbials, anti-fungal, cardiovascular agents, diuretics, cytostatics, anti-neoplastic agents, anti-viral agents, anti-glaucoma agents, anti-depressants, sympathomimetics, hypoglycaemics, diagnostic agents, anti-cough, physic energizers, anti-parkinson agents, local anesthetics, muscle contractants, anti-malarials, hormonal agents, contraceptives, anorexic, anti-arthritic, anti-diabetic, anti-hypertensive, anti-pyretic, anti-cholingergic, bronchodilator, central nervous system, inotropic, vasodilator, vasoconstrictor, decongestant, hematinic, electrolyte supplement, germicidal, parasympathetolytic, parasymphatethomimetic, antiemetic, psychostimulant, vitamin, beta-blockers, H-2 blocker, beta-2 agonist, counterirritants, coagulating modifying agents, stimulants, anti-hormones, drug-antagonists, lipid-regulating agents, uricosurics, cardiac glycosides, ergot and derivatives thereof, expectorants, muscle relaxants, anti-histamines, purgatives, contrast materials, radiopharmaceuticals, imaging agents, anti-allergic agents, and combinations thereof.

3. The formulation of claim 1, wherein the concentration of the one or more active agents is from about 0.1% to about 90% by weight of the composition, from about 0.5% to about 20% by weight of the composition, or from about 1% to about 10% by weight of the composition.

4. The formulation of claim 1, wherein the one or more enteric materials is selected from the group consisting of cellulose acetate phthalate, alginates, alkali-soluble acrylic resins, hydroxypropyl methylcellulose phthalate, methacrylate-methacrylic acid co-polymers, polyvinyl acetate phthalate, styrol maleic acid copolymers, and combinations thereof.

5. The formulation of claim 1, wherein the concentration of the one or more enteric materials is from bout 0.1% to about 20% by weight of the compositions, from about 1 to about 15% by weight of the composition, or from about 5 to about 10% by weight of the composition.

6. The formulation of claim 1, wherein the core or central layer further comprises one or more non-enteric polymeric materials that modulate the release of the calcium channel blocker.

7. The formulation of claim 6, wherein the one or more non-enteric polymeric materials are selected from the group consisting of crosslinked polyvinylpyrrolidone, hydroxypropylmethylcellulose, hydroxypropylcellulose, crosslinked sodium carboxymethylcellulose, carboxymethyl starch, acrylic and methacrylic acid polymers and copolymers, polyesters, polyanhydrides, polymethylvinylether/anhydride copolymers, potassium methacrylate-divinylbenzene copolymer, polyvinylalcohols, glucan, scleroglucan, mannan, starch and derivatives thereof, betacyclodextrins, cyclodextrin derivatives containing linear and/or branched polymeric chains, and combinations thereof.

8. The formulation of claim 7, wherein the one or more polymeric materials that modulate the release of the calcium channel blocker are present in a concentration from about 1% to about 90% by weight of the core, or from about 10% to about 45% by weight of the core.

9. The formulation of claim 1, wherein the one or more swellable, erodible, or gellable polymers are selected from the group consisting of hydroxypropylmethylcellulose, carboxyvinyl polymers;

polyvinylalcohols;

glucans, scleroglucans;

mannans;

xantans;

alginates and derivatives thereof;

polyanhydrides;

polyaminoacids;

methylvinylether/maleic anhydride copolymers;

carboxymethylcellulose and derivatives thereof;

ethylcellulose, methylcellulose, and other cellulosic derivatives; and

combinations thereof.

10. The formulation of claim 1, wherein the concentration of the one or more swellable, erodible, and/or gellable polymers is from about 5% and to about 90% by weight of the barrier layer(s) or from about 25% and to about 75% by weight of the barrier layer(s).

11. The formulation of claim 10, wherein the polymer is hydroxypropylmethylcellulose.

12. The formulation of claim 1, wherein the core and/or the barrier layer further comprise one or more excipients selected from the group consisting of plasticizers, diluents, binders, lubricants, surfactants, pH modifying agents, anti-adherents, disintegrators, fillers, pigments, colorants, stabilizing agents, flavoring agents, glidants, and combinations thereof.

13. The formulation of claim 1, wherein the formulation is in the form of a tablet or caplet.

14. The formulation of claim 1, wherein the central layer and/or the barrier layer further comprises one or more adjuvants that further modulate the release of the active agent selected from the group consisting of glyceryl monostearate, triglyceride derivatives, semi-synthetic glycerides, hydrogenated castor oil, glyceryl palmitostearate, cetyl alcohol, polyvinylpyrrolidone, glycerol, ethylcellulose, methylcellulose, sodium carboxymethylcellulose, magnesium stearate, stearic acid, talc, sodium benzoate, boric acid, polyoxyethylenglycols, colloidal silica, and combinations thereof.

15. The formulation of claim 1, further comprising one or more coating materials which modulate release of the active agent.

16. The formulation of claim 15, wherein the one or more coating materials are selected from the group consisting of immediate release coatings, taste masking coatings, sustained released coatings, enteric coatings, delayed release coatings, and combinations thereof.

17. A method of treating a cardiovascular disorder, the method comprising administering to a patient in need thereof a formulation comprising

(a) a core comprising one or more active agents and one or more enteric materials;

and optionally

(b) one or more barrier layers comprising one or more swellable, erodible, or gellable polymers,

wherein, upon administration to a subject, the active agent is released with an ascending release rate in response to the changes in pH as the dosage formulation descends the GI tract.

18. The method of claim 17, wherein the concentration of the one or more active agents is from about 0.1% to about 90% by weight of the composition, from about 0.5% to about 20% by weight of the composition, or from about 1% to about 10% by weight of the composition.

19. The method of claim 17, wherein the one or more enteric materials is selected from the group consisting of cellulose acetate phthalate, alginates, alkali-soluble acrylic resins, hydroxypropyl methylcellulose phthalate, methacrylate-methacrylic acid co-polymers, polyvinyl acetate phthalate, styrol maleic acid copolymers, and combinations thereof.

20. The method of claim 17, wherein the concentration of the one or more enteric materials is from bout 0.1% to about 20% by weight of the compositions, from about 1 to about 15% by weight of the composition, or from about 5 to about 10% by weight of the composition.

21. The method of claim 17, wherein the core or central layer further comprises one or more non-enteric polymeric materials that modulate the release of the calcium channel blocker.

22. The method of claim 17, wherein the one or more non-enteric polymeric materials are selected from the group consisting of crosslinked polyvinylpyrrolidone, hydroxypropylmethylcellulose, hydroxypropylcellulose, crosslinl(ed sodium carboxymethylcellulose, carboxymethyl starch, acrylic and methacrylic acid polymers and copolymers, polyesters, polyanhydrides, polymethylvinylether/alnhydride copolymers, potassium methacrylate-divinylbenzene copolymer, polyvinylalcohols, glucan, scleroglucaln, mannan, starch and derivatives thereof betacyclodextrins, cyclodextrin derivatives containing linear and/or branched polymeric chains, and combinations thereof.

23. The method of claim 17, wherein the one or more polymeric materials that modulate the release of the calcium channel blocker are present in a concentration from about 1% to about 90% by weight of the core, or from about 10% to about 45% by weight of the core.

24. The method of claim 17, wherein the one or more swellable, erodible, or gellable polymers are selected from the group consisting of hydroxypropylmethylcellulose, carboxyvinyl polymers;

polyvinylalcohols;

glucans, scleroglucans;

mannans;

xantans;

alginates and derivatives thereof;

polyanhydrides;

polyaminoacids;

methylvinylether/maleic anhydride copolymers;

carboxymethylcellulose and derivatives thereof;

ethylcellulose, methylcellulose, and other cellulosic derivatives; and

combinations thereof.

25. The method of claim 17, wherein the concentration of the one or more swellable, erodible, and/or gellable polymers is from about 5% and to about 90% by weight of the barrier layer(s) or from about 25% and to about 75% by weight of the barrier layer(s).