Dual controlled release dosage form

• US 20060204578A1
• Filed: 02/15/2006
• Published: 09/14/2006
• Est. Priority Date: 11/06/2001
• Status: Active Grant

• Current Assignee: Osmotica Kereskedelmi Es Szolgaltato Kft (Osmotica Pharmaceuticals Plc)
• Original Assignee: Osmotica Kereskedelmi Es Szolgaltato Kft (Osmotica Pharmaceuticals Plc)
• Inventors: Vergez, Juan A., Ricci, Marcelo A.
• Granted Patent: US 8,329,217 B2
• Time in Patent Office: Days
• US Class Current: 424/473
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/401 Proline; Derivatives thereof, e.g. captopril
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 31/4025 not condensed and containing further heterocyclic rings, e.g. cromakalim
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 31/5517 condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• 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: A61K 9/4808 : characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/5042 : Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5078 : with drug-free core

Abstract

A dosage form that provides a controlled release of at least two different active agents is provided. Particular embodiments include a dosage form that provides therapeutically effective levels of a first active agent and a second active agent in a mammal for an extended period of time following oral administration. An osmotic device containing a bi-layered core is provided. The osmotic device provides a dual controlled release of both drugs from the core. The layers of the core are in stacked, substantially concentric or substantially eccentric arrangement.

Claims

1. ) A dual controlled release osmotic device comprising:

a) a core comprising a first active agent-containing controlled release layer and a second active agent-containing controlled release layer in direct contact therewith; and

b) a membrane surrounding the core, wherein the membrane comprises at least one preformed passageway in communication with at least one of the first and second active agent-containing controlled release layers;

whereby the osmotic device provides a controlled release of the first active agent through the at least one preformed passageway according to a first release profile and the second layer provides a controlled release of the second active through the at least one preformed passageway according to a second release profile.

2. ) The osmotic device of claim 1, wherein the layers are in stacked arrangement and in contact with one another.

3. ) The osmotic device of claim 1, wherein the second active agent-containing layer surrounds the first active agent-containing layer.

4. ) The osmotic device of claim 2 or 3, wherein the osmotic device comprises at least one first preformed passageway in communication with the first active agent-containing layer and at least one second preformed passageway in communication with the second active agent-containing layer.

5. ) The osmotic device of claim 2 or 3, wherein the membrane comprises at least one preformed passageway in communication with both the first and second active agent-containing layers.

6. ) The osmotic device of claim 2 or 3, wherein the membrane comprises at least two preformed passageways and at least one of the two preformed passageways is plugged with a water soluble or water erodible material.

7. ) The osmotic device of claim 2 or 3, wherein the membrane comprises at least two preformed passageways both of which are plugged with a water soluble or water erodible material, wherein the material plugging the first passageway is the same as the material plugging the second passageway.

8. ) The osmotic device of claim 2 or 3, wherein the membrane comprises at least two preformed passageways both of which are plugged with a water soluble or water erodible material, wherein the material plugging the first passageway is different than the material plugging the second passageway.

9. ) The osmotic device of claim 2 or 3 further comprising at least one external coat exterior to the membrane.

10. ) The osmotic device of claim 9, wherein the external coat is independently selected at each occurrence from water soluble and water erodible.

11. ) The osmotic device of claim 9, wherein the external coat is independently selected at each occurrence from inert and drug-containing.

12. ) The osmotic device of claim 9, wherein the external coat is independently selected at each occurrence from microporous, permeable, semipermeable and impermeable.

13. ) The osmotic device of claim 2 or 3 further comprising at least one internal coat interposed the core and the membrane.

14. ) The osmotic device of claim 13, wherein the internal coat is independently selected at each occurrence from water soluble and water erodible.

15. ) The osmotic device of claim 13, wherein the internal coat is independently selected at each occurrence from inert and drug-containing.

16. ) The osmotic device of claim 13, wherein the internal coat is independently selected at each occurrence from microporous, permeable, semipermeable and impermeable.

17. ) The osmotic device of claim 2 or 3, wherein the first drug and the second drug are released sequentially or in an overlapping manner when the osmotic device is exposed to an aqueous environment.

18. ) The osmotic device of claim 1 further comprising an external coat surrounding the membrane, and the membrane comprises at least a first preformed passageway and at least a second preformed passageway, wherein the first passageway has been formed after application of the external coat to the membrane, and the second passageway has been formed before application of the external coat to the membrane such that the second passageway is plugged by the external coat, and release of the second drug begins after release of the first drug has started.

19. ) The osmotic device of claim 1 further comprising an external coat surrounding the membrane, and the membrane comprises at least a first preformed passageway and at least a second preformed passageway, wherein the first and second passageways have been formed before application of the external coat to the membrane;

and the first and second passageways are plugged by the external coat.

20. ) The osmotic device of claim 19, wherein release of the first drug and the second drug is delayed for a period of time after exposure to an aqueous environment.

21. ) The osmotic device of any one of claims 1, 2 or 3, wherein each drug is independently released according to a timed, targeted, pseudo-first order, first order, pseudo-zero order, zero-order, and/or delayed release profile.

22. ) The osmotic device of claim 4, wherein each drug is independently released according to a timed, targeted, pseudo-first order, first order, pseudo-zero order, zero-order, and/or delayed release profile.

23. ) The osmotic device of claim 5, wherein each drug is independently released according to a timed, targeted, pseudo-first order, first order, pseudo-zero order, zero-order, and/or delayed release profile.

24. ) The osmotic device of claim 6, wherein each drug is independently released according to a timed, targeted, pseudo-first order, first order, pseudo-zero order, zero-order, and/or delayed release profile.

25. ) The osmotic device of claim 7, wherein each drug is independently released according to a timed, targeted, pseudo-first order, first order, pseudo-zero order, zero-order, and/or delayed release profile.

26. ) The osmotic device of claim 8, wherein each drug is independently released according to a timed, targeted, pseudo-first order, first order, pseudo-zero order, zero-order, and/or delayed release profile.

27. ) The osmotic device of claim 9, wherein each drug is independently released according to a timed, targeted, pseudo-first order, first order, pseudo-zero order, zero-order, and/or delayed release profile.

28. ) The osmotic device of claim 13, wherein each drug is independently released according to a timed, targeted, pseudo-first order, first order, pseudo-zero order, zero-order, and/or delayed release profile.

29. ) The osmotic device of claim 16, wherein each drug is independently released according to a timed, targeted, pseudo-first order, first order, pseudo-zero order, zero-order, and/or delayed release profile.

30. ) The osmotic device of claim 17, 18 or 19, wherein each drug is independently released according to a timed, targeted, pseudo-first order, first order, pseudo-zero order, zero-order, and/or delayed release profile.

31. ) The osmotic device of claim 1, wherein the membrane has at least two preformed passageways, at least one passageway is in communication with the first composition and at least one passageway is in communication with the second composition.

48. ) The osmotic device of claim 1 or 32, wherein the first and second active agents are independently selected at each occurrence from the group consisting of an antibiotic agent, antihistamine agent, decongestant, anti-inflammatory agent, antiparasitic agent, antiviral agent, local anesthetic, antifungal agent, amoebicidal agent, trichomonocidal agent, analgesic agent, anti-arthritic agent, anti-asthmatic agent, anticoagulant agent, anticonvulsant agent, anti-Alzheimer'"'"'s disease agent antidepressant agent, antidiabetic agent, antineoplastic agent, anti-psychotic agent, neuroleptic agent, antihypertensive agent, hypnotic agent, sedative agent, anxiolytic energizer agent, anti-Parkinson agent, muscle relaxant agent, antimalarial agent, hormonal agent, contraceptive agent, sympathomimetic agent, hypoglycemic agent, antilipemic agent, ophthalmic agent, electrolytic agent, diagnostic agent, prokinetic agent, gastric acid secretion inhibitor agent, anti-ulcerant agent, anti-flatulent agent, anti-incontinence agent, and cardiovascular agent.

49. ) The osmotic device of claim 1 or 32, wherein first and second active agents are selected as follows:

a) the first active agent is a prokinetic agent and the second active agent is a gastric acid secretion inhibitor agent;

b) the first active agent is a decongestant and the second active agent is an antihistamine;

c) the first active agent is a first anti-incontinence agent and the second active agent is a different second anti-incontinence agent;

d) the first active agent is a first antihypertensive agent and the second active agent is a different second antihypertensive agent;

e) the first active agent is an antidepressant agent and the second active agent is an anti-psychotic agent;

f) the first active agent is a first analgesic or anti-inflammatory agent, and the second active agent is a different second analgesic or anti-inflammatory agent;

g) the first active agent is an antiviral agent and the second active agent is an antihistamine agent;

h) the first active agent is a muscle relaxant agent and the second active agent is an anti-inflammatory or analgesic agent;

i) the first active agent is an antidiabetic agent and the second active agent is a different antidiabetic agent;

j) the first active agent is an antidepressant and the second active agent is an agent for the treatment of Alzheimer'"'"'s disease;

k) the first active agent is an anticonvulsant and the second active agent is an anti-psychotic agent;

l) the first active agent is an antilipemic agent and the second active agent is a different antilipemic agent;

m) the first active agent is an antidepressant and the second active agent is an anti-Parkinson agent;

or

n) the first active agent is an antidiabetic agent and the second active agent is an antilipemic agent.

50. ) The osmotic device of claim 1 or 32, wherein the first and second active agents are selected as follows:

a) the first active agent is pridinol and the second active agent is a selective or specific COX-II inhibitor agent;

b) the analgesic and anti-inflammatory agents are selected from the group consisting of an non-steroidal anti-inflammatory agent, a steroidal, anti-inflammatory agent, an opioid receptor agonist agent, and a selective or specific COX-II inhibitor agent;

c) the antihypertensive agent is selected from the group consisting of a calcium channel blocker agent, an angiotensin converting enzyme inhibitor agent, a diuretic agent and a beta-adrenergic antagonist agent;

d) the antidiabetic agent is selected from the following main groups of oral antidiabetic drugs available;

sulphonylureas, tolbutamide, chlorpropamide, tolazamide, acetohexamide, glibenclamide, gliclazide, 1-butyl-3-metanilylurea, carbutamide, glibonuride, glipizide, glyburide, gliquidone, glisoxepid, glybuthiazole, glibuzole, glyhexamide, glymidine, glypinamide, phenbutamide, and tolcyclamide;

thiazolidinediones, glitazones, rosiglitazone, pioglitazone, and troglitazone;

biguanidines, metformin;

nateglinide; and

repaglinide

e) the anti-Alzheimer'"'"'s disease agent is selected from the group consisting of memantine, donepexil, galantamine, rivastigmine, and tacrine;

f) the antidepressant is selected from the group consisting of venlafaxine, amitriptyline, citalopram, bupropion, clomipramine, desipramine, nefazodone, fluoxetine, doxepin, fluvoxamine, maprotiline, imipramine, mirtazapine, nortriptyline, paroxetine, phenelzine, tranylcypromine, protriptyline, sertraline, trazodone, trimipramine, and amoxapine;

g) the anticonvulsant is selected from the group consisting of carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, topiramate, and zonisamide;

h) the antipsychotic agent is selected from the group consisting of chlorpromazine, clozapine, fluphenazine, haloperidol, loxapine, mesoridazine, molindone, olanzapine, quetiapine, ziprasidone, risperidone, perphenazine, pimozide, prochlorperazine, thioridazine, thiothixene, and trifluoperazine;

i) the antilipemic agent is selected from the group consisting of cholestyramine, cholestipol, nicotinic acid, clofibrate, gemfibrozil, dextrothyroxine sodium, prabucol, mevastatin, lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, pitavastatin, and ezetimibe;

j) the anti-Parkinson agent is selected from the group consisting of levodopa, benztropine mesylate, benzeraside, carbidopa, bromocriptine, pergolide, selegiline, ropirinol, pramipexole, amantadine, entacapone, tolcapone, biperiden, carbelogine, apomorphine, lisuride, prociclidine, and trihexylphenidyl;

or

k) the first active agent is pridinol and the second active agent is licofelone.

32. ) A dual controlled release osmotic device comprising:

a) a core comprising a first controlled release composition comprising a first active agent and at least one pharmaceutical excipient, and a different second controlled release composition comprising a second active agent and at least one pharmaceutical excipient, wherein the first and second compositions contact one another and are in stacked arrangement; and

b) a membrane enveloping the core and having at least one preformed passageway to permit a controlled release of the first and second drugs from the core when the osmotic device is exposed to an aqueous environment, wherein at least one passageway is in communication with the first composition.

33. ) The osmotic device of claim 32, wherein the membrane is semipermeable.

34. ) The osmotic device of claim 32 further comprising at least one external coat exterior to the membrane.

35. ) The osmotic device of claim 34, wherein the external coat is independently selected at each occurrence from water soluble and water erodible.

36. ) The osmotic device of claim 34, wherein the external coat is independently selected at each occurrence from inert and drug-containing.

37. ) The osmotic device of claim 34, wherein the external coat is independently selected at each occurrence from microporous, permeable, semipermeable and impermeable.

38. ) The osmotic device of claim 32 further comprising at least one internal coat interposed the core and the membrane.

39. ) The osmotic device of claim 38, wherein the internal coat is independently selected at each occurrence from water soluble and water erodible.

40. ) The osmotic device of claim 38, wherein the internal coat is independently selected at each occurrence from inert and drug-containing.

41. ) The osmotic device of claim 38, wherein the internal coat is independently selected at each occurrence from microporous, permeable, semipermeable and impermeable.

42. ) The osmotic device of claim 32, wherein the first drug and the second drug are released sequentially or in an overlapping manner when the osmotic device is exposed to an aqueous environment.

43. ) The osmotic device of claim 32 further comprising an external coat surrounding the semipermeable membrane, wherein the first passageway has been formed after application of the external coat to the semipermeable membrane and the second passageway has been formed before application of the external coat to the semipermeable membrane such that the second passageway is plugged by the external coat and release of the second drug begins after release of the first drug has started.

44. ) The osmotic device of claim 32 further comprising an external coat surrounding the semipermeable membrane, wherein the first and second passageways have been formed before application of the external coat to the semipermeable membrane;

the first and second passageways are plugged by the external coat; and

release of the first drug and the second drug is delayed for a period of time after exposure to an aqueous environment.

45. ) The osmotic device of claim 33, wherein the first drug and the second drug are released sequentially or in an overlapping manner when the osmotic device is exposed to an aqueous environment.

46. ) The osmotic device of claim 32, wherein the membrane has at least two preformed passageways, at least one passageway is in communication with the first composition and at least one passageway is in communication with the second composition.

47. ) The osmotic device of claim 32, 33, 34, 38, 42 or 45, wherein each drug is independently released according to a timed, targeted, pseudo-first order, first order, pseudo-zero order, zero-order, and/or delayed release profile.