Rupturing controlled release device having a preformed passageway

• US 8,029,822 B2
• Filed: 05/21/2004
• Issued: 10/04/2011
• Est. Priority Date: 05/22/2003
• Status: Active Grant

• Current Assignee: Osmotica Kereskedelmi Es Szolgaltato Kft (Osmotica Pharmaceuticals Plc), Osmotica Pharmaceutical Corporation (Osmotica Pharmaceuticals Plc)
• Original Assignee: Osmotica Kereskedelmi Es Szolgaltato Kft (Osmotica Pharmaceuticals Plc)
• Inventors: Vergez, Juan A, Faour, Joaquina
• Primary Examiner(s): Kishore; Gollamudi
• Assistant Examiner(s): Maewall; Snigdha
• Application Number:
  US10/851,866
• Publication Number:
  US 20050008702A1
• Time in Patent Office: 2,692 Days
• Field of Search: 424/463, 424/473
• US Class Current: 424/463
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer

Abstract

The present invention provides a simple and improved osmotic device that is capable of providing a controlled release of active agent contained in the core first through a preformed passageway and then through an in situ formed second passageway into an environment of use. One or both of the passageways optionally increases in size during use of the osmotic device. The preformed passageway and/or the second passageway increase the release rate of the active agent, enable the release of large particles containing active agent, and/or enable the release of active agents that are substantially insoluble in the environment of use. By virtue of the in situ formation of the second aperture, the device is able to release a greater overall percentage of active agent than it would release in absence of the second aperture.

Claims

1. A rupturing controlled release device comprising:

a) a core comprising an active agent and, optionally, at least one excipient, and b) a wall enclosing the core and having a weakened section and a preformed passageway there through, wherein the wall ruptures at the weakened section during use due to an increase of internal osmotic pressure of the core during use of the device to form a second passageway by breakage of the wall at a location spaced away from the preformed passageway such that active agent is released over an extended period of time from both passageways.

2. The controlled release device of claim 1, wherein the device is an osmotic device comprising:

a) a core comprising at least one active agent, at least one osmopolymer, and, optionally, at least one excipient;

b) a wall surrounding the core, the wall comprising a semipermeable membrane and optionally one or more other coatings or membranes; and

c) a preformed passageway in the wall for at least initial release of the contents of the core, wherein the wall ruptures during due to an increase of internal osmotic pressure of the core during use of the device to form a spaced away second aperture by breakage of the wall such that the device provides an increased release rate of active agent after rupture as compared to before rupture of the wall, and the device provides a controlled release of the contents from the core.

3. The device of claim 1, wherein the release rate of active agent increases over time during use.

4. The device of claim 1 or 2, wherein at least 80% of the active agent is released by the end of use.

5. The device of claim 1 or 2, wherein the core comprises a swellable material, and the second passageway forms due to an increase of internal osmotic pressure of the core during use of the device.

6. The device of claim 1 or 2, wherein the preformed passageway is formed by mechanical means during manufacture of the osmotic device.

7. The device of claim 1 or 2, wherein the preformed passageway is plugged with a soluble material that dissolves during use of the osmotic device.

8. The device of claim 1 or 2, wherein the wall ruptures in a predetermined manner.

9. The device of claim 1 or 2, wherein the wall ruptures in a random manner.

10. The device of claim 1 or 2, wherein the second passageway is smaller than or approximates the size of the preformed passageway.

11. The device of claim 1 or 2, wherein the second passageway is larger than the preformed passageway.

12. The device of claim 1 or 2, wherein the second passageway forms at a predetermined location of the wall.

13. The device of claim 1 or 2, wherein the core comprises a nucleus that is coated with active agent and at least one excipient.

14. The device of claim 1, 2, or 3, wherein the exterior of the wall has at least one coating that effects the operation of the osmotic device in a manner according to the properties of the coating.

15. The device of claim 1 or 2, wherein the second passageway is formed more than about one hour after exposure of the device to an environment of use.

16. The device of claim 6, wherein the second passageway is formed more than about one hour after exposure of the device to an environment of use.

17. The device of claim 1 or 2, wherein the second passageway is formed more than about three hours after exposure of the device to an environment of use.

18. The device of claim 1 or 2, wherein the core comprises a first layer comprising the active agent and the at least one excipient and a second layer comprising a swellable material and/or an osmotic agent.

19. The device of claim 1 or 2, wherein the core comprises a nucleus comprising a swellable material and/or an osmotic agent and a coating surrounding the nucleus and comprising the active substance and the at least one excipient.

20. The device of claim 1 further comprising one or more coatings on the exterior of the wall, wherein the one or more coatings are independently selected at each occurrence from the group consisting of a drug-containing coating, a release rate modifying coating, a porous coating;

a soluble coating, an insoluble coating, a semipermeable membrane; and

a delayed release coating.

21. The device of claim 1 or 2, wherein the active agent is selected from the group consisting of albuterol, atenolol, acyclovir, amlodipine besylate, amoxicillin trihydrate, acetaminophen, allopurinol, atorvastatin calcium, aspirin, alprazolam, azithromycin dihydrate, caffeine monohydrate, candesartan cilexetil, carisoprodol, cimetidine, ciprofloxacin HCl, ciprofloxacin HCl monohydrate, citalopram, carbamazepine, carvedilol, celecoxib, clonazepam, clopidogrel bisulfate, diazepam, doxazosin mesylate, enalapril maleate, esomeprazole magnesium, eprosartan mesylate, fexofenadine HCl, fluconazole, fluoxetine HCl, galanthamine HBr, gemfibrozil, felodipine, glipizide, glyburide, hydrochlorothiazide, ibuprofen, lamotrigine, lansoprazole, loratadine, lorazepam, modafinil, memantine HCl, metronidazole, naproxen, nifedipine, nisoldipine, olanzapine, omeprazole, olmersartan medoxomil, paroxetine HCl, prednisone, pindolol, pioglitazone HCl, raloxifene HCl, ramipril, risperidone, rofecoxib, sertraline HCl, sildenafil citrate, simvastatin, tegaserod maleate, temazepan, telmisartan, trazodone HCl, triamterene, valsartan, vardenafil HCl, and zolpidem tartrate.

22. The device of claim 5, wherein the swellable material, when present, is selected from the group consisting of hydroxypropyl methylcellulose, poly(vinlypyrrolidone)-(vinyl acetate) copolymer, poly(vinylpyrrolidone), methyl methacrylate, calcium pectinate, poly(ethylene-vinyl acetate), hydroxylalkyl alkylcellulose, polyvinylalcohol, polyethylene oxide, a blend of gelatin and polyvinyl-pyrrolidone, gelatin, glucose, saccharide, povidone, copovidone, and polysaccharide gum.

23. The device of claim 18, wherein the swellable material, when present, is selected from the group consisting of hydroxypropyl methylcellulose, poly(vinlypyrrolidone)-(vinyl acetate) copolymer, poly(vinylpyrrolidone), methyl methacrylate, calcium pectinate, poly(ethylene-vinyl acetate), hydroxylalkyl alkylcellulose, polyvinylalcohol, polyethylene oxide, a blend of gelatin and polyvinyl-pyrrolidone, gelatin, glucose, saccharide, povidone, copovidone, and polysaccharide gum.

24. The device of claim 19, wherein the swellable material, when present, is selected from the group consisting of hydroxypropyl methylcellulose, poly(vinlypyrrolidone)-(vinyl acetate) copolymer, poly(vinylpyrrolidone), methyl methacrylate, calcium pectinate, poly(ethylene-vinyl acetate), hydroxylalkyl alkylcellulose, polyvinylalcohol, polyethylene oxide, a blend of gelatin and polyvinyl-pyrrolidone, gelatin, glucose, saccharide, povidone, copovidone, and polysaccharide gum.

25. The device of claim 2, wherein the at least one osmopolymer is selected from the group consisting of hydroxypropyl methylcellulose, poly(vinlypyrrolidone)-(vinyl acetate) copolymer, poly(vinylpyrrolidone), methyl methacrylate, calcium pectinate, poly(ethylene-vinyl acetate), hydroxylalkyl alkylcellulose, polyvinylalcohol, polyethylene oxide, a blend of gelatin and polyvinyl-pyrrolidone, gelatin, glucose, saccharide, povidone, copovidone, and polysaccharide gum.

26. The device of claim 1 or 2, wherein:

the core further comprises a surfactant, a diluent, an osmagent, and a binder; and

the wall comprises one or more cellulose esters and a plasticizer.

27. The device of claim 26, wherein:

the surfactant is selected from the group consisting of polysorbate, fatty amine oxides, fatty acid alkanolamides, and poly(oxyethylene)-block-poly(oxypropylene) copolymers, diethylene glycol monostearate, sodium lauryl sulfate, sorbitan monooleate, polyoxyethylene sorbitan fatty acid esters, polysorbate, bile salts, and glyceryl monostearate;

the diluent is selected from the group consisting of microcrystalline cellulose, lactose, sucrose, mannitol, cellulose, starch, sorbitol, dibasic calcium phosphate, and calcium carbonate;

the osmagent is selected from the group consisting of sodium chloride, salt, mannitol, acid, sugar, base, calcium salt, sodium salt, and lactose;

the binder is selected from the group consisting of poly(vinylpyrrolidone), povidone, sodium carboxymethylcellulose, alginic acid, poly(ethylene glycol), guar gum, polysaccharide, bentonite clay, sugar, poloxamer, collagen, albumin, gelatin, poly(propylene glycol), and poly(ethylene oxide);

the cellulose esters are selected from the group consisting of cellulose acetate, cellulose acetate phthalate, cellulose acetate trimelletate, cellulose acylate, and cellulose fatty acid ester; and

the plasticizer is selected from the group consisting of poly(ethylene glycol), low molecular weight polymer, citrate ester, triacetin, propylene glycol, glycerin, sorbitol lactate, ethyl lactate, butyl lactate, ethyl glycolate, and dibutylsebacate.

28. The device of claim 26, wherein:

the active agent is nifedipine present in an amount ranging from about 30-100 mg;

a surfactant is present in an amount ranging from about 0.10-7.50 mg;

a diluent is present in an amount ranging from about 20.00-270.00 mg;

an osmagent is present in an amount ranging from about 45.00-640.00 mg;

a binder is present in an amount ranging from about 10.00-150.00 mg;

at least one osmopolymer is present in an amount ranging from about 3.00-345.00 mg;

cellulose esters are present in an amount ranging from about 17.50-50.00 mg; and

a plasticizer is present in an amount ranging from about 0.50-7.00 mg.

29. The device of claim 26, wherein the active agent is selected from the group consisting of doxazosin, nifedipine, felodipine, carisoprodol, and a pharmaceutically acceptable salt thereof.

30. The device of claim 5, wherein:

the core further comprises a surfactant, a diluent, an osmagent, and a binder; and

the wall comprises one or more cellulose esters and a plasticizer.

31. The device of claim 30, wherein:

the surfactant is selected from the group consisting of polysorbate, fatty amine oxides, fatty acid alkanolamides, and poly(oxyethylene)-block-poly(oxypropylene) copolymers, diethylene glycol monostearate, sodium lauryl sulfate, sorbitan monooleate, polyoxyethylene sorbitan fatty acid esters, polysorbate, bile salts, and glyceryl monostearate;

the diluent is selected from the group consisting of microcrystalline cellulose, lactose, sucrose, mannitol, cellulose, starch, sorbitol, dibasic calcium phosphate, and calcium carbonate;

the osmagent is selected from the group consisting of sodium chloride, salt, mannitol, acid, sugar, base, calcium salt, sodium salt, and lactose;

the binder is selected from the group consisting of poly(vinylpyrrolidone), povidone, sodium carboxymethylcellulose, alginic acid, poly(ethylene glycol), guar gum, polysaccharide, bentonite clay, sugar, poloxamer, collagen, albumin, gelatin, poly(propylene glycol), and poly(ethylene oxide);

the cellulose esters are selected from the group consisting of cellulose acetate, cellulose acetate phthalate, cellulose acetate trimelletate, cellulose acylate, and cellulose fatty acid ester; and

the plasticizer is selected from the group consisting of poly(ethylene glycol), low molecular weight polymer, citrate ester, triacetin, propylene glycol, glycerin, sorbitol lactate, ethyl lactate, butyl lactate, ethyl glycolate, and dibutylsebacate.

32. The device of claim 30, wherein the active agent is selected from the group consisting of doxazosin, nifedipine, felodipine, carisoprodol, and a pharmaceutically acceptable salt thereof.

33. The device of claim 18, wherein:

the core further comprises a surfactant, a diluent, an osmagent, and a binder; and

the wall comprises one or more cellulose esters and a plasticizer.

34. The device of claim 33, wherein:

the surfactant is selected from the group consisting of polysorbate, fatty amine oxides, fatty acid alkanolamides, and poly(oxyethylene)-block-poly(oxypropylene) copolymers, diethylene glycol monostearate, sodium lauryl sulfate, sorbitan monooleate, polyoxyethylene sorbitan fatty acid esters, polysorbate, bile salts, and glyceryl monostearate;

the diluent is selected from the group consisting of microcrystalline cellulose, lactose, sucrose, mannitol, cellulose, starch, sorbitol, dibasic calcium phosphate, and calcium carbonate;

the osmagent is selected from the group consisting of sodium chloride, salt, mannitol, acid, sugar, base, calcium salt, sodium salt, and lactose;

the binder is selected from the group consisting of poly(vinylpyrrolidone), povidone, sodium carboxymethylcellulose, alginic acid, poly(ethylene glycol), guar gum, polysaccharide, bentonite clay, sugar, poloxamer, collagen, albumin, gelatin, poly(propylene glycol), and poly(ethylene oxide);

the cellulose esters are selected from the group consisting of cellulose acetate, cellulose acetate phthalate, cellulose acetate trimelletate, cellulose acylate, and cellulose fatty acid ester; and

the plasticizer is selected from the group consisting of poly(ethylene glycol), low molecular weight polymer, citrate ester, triacetin, propylene glycol, glycerin, sorbitol lactate, ethyl lactate, butyl lactate, ethyl glycolate, and dibutylsebacate.

35. The device of claim 33, wherein the active agent is selected from the group consisting of doxazosin, nifedipine, felodipine, carisoprodol, and a pharmaceutically acceptable salt thereof.

36. The device of claim 19, wherein:

the core further comprises a surfactant, a diluent, an osmagent, and a binder; and

the wall comprises one or more cellulose esters and a plasticizer.

37. The device of claim 36, wherein:

the surfactant is selected from the group consisting of polysorbate, fatty amine oxides, fatty acid alkanolamides, and poly(oxyethylene)-block-poly(oxypropylene) copolymers, diethylene glycol monostearate, sodium lauryl sulfate, sorbitan monooleate, polyoxyethylene sorbitan fatty acid esters, polysorbate, bile salts, and glyceryl monostearate;

the diluent is selected from the group consisting of microcrystalline cellulose, lactose, sucrose, mannitol, cellulose, starch, sorbitol, dibasic calcium phosphate, and calcium carbonate;

the osmagent is selected from the group consisting of sodium chloride, salt, mannitol, acid, sugar, base, calcium salt, sodium salt, and lactose;

the binder is selected from the group consisting of poly(vinylpyrrolidone), povidone, sodium carboxymethylcellulose, alginic acid, poly(ethylene glycol), guar gum, polysaccharide, bentonite clay, sugar, poloxamer, collagen, albumin, gelatin, poly(propylene glycol), and poly(ethylene oxide);

the cellulose esters are selected from the group consisting of cellulose acetate, cellulose acetate phthalate, cellulose acetate trimelletate, cellulose acylate, and cellulose fatty acid ester; and

the plasticizer is selected from the group consisting of poly(ethylene glycol), low molecular weight polymer, citrate ester, triacetin, propylene glycol, glycerin, sorbitol lactate, ethyl lactate, butyl lactate, ethyl glycolate, and dibutylsebacate.

38. The device of claim 36, wherein the active agent is selected from the group consisting of doxazosin, nifedipine, felodipine, carisoprodol, and a pharmaceutically acceptable salt thereof.

41. The device of claim 2, wherein the one or more coatings is present and is a drug-containing coating.

42. The device of claim 41, wherein the active agent is a first drug from a first therapeutic class and the drug-containing coating contains a different second drug from a different therapeutic class.

43. The device of claim 42, wherein the first drug and second drug are independently selected at each occurrence from the group consisting of central nervous system agent, drug that acts on α

-adrenergic receptors, electrolyte, ophthalmic agent, nutritional agent, antilipemic agent, phosphodiesterase inhibitor, β

-blocker, diuretic, sympathomimetic agent, anti-Alzheimer disease agent, anti-Parkinson disease agent, muscle relaxant, local anesthetic, anti-spasmodic, muscle contractant, tranquilizer, antihypertensive agent, hypnotic agent, sedative, antipsychotic agent, estrogen antagonist-agonist agent, steroid, antidiabetic agent, antidepressant agent, anticonvulsant agent, psychic energizer, anticoagulant agent, antiasthma agent, antihistamine agent, decongestant, analgesic agent, anti-inflammatory agent, antiviral agent, antiparasitic agent, antibacterial agent, cardiovascular agent, nutrient, hematological agent, endocrine agent, metabolic agent, renal agent, genitourinary agent, respiratory agent, gastrointestinal agent, anti-infective agent, biologic agent, immunological agent, dermatological agent, antineoplastic agent and diagnostic agent.

44. The device of claim 43, wherein

a) the anti-inflammatory drug is present and is selected from the group consisting of rofecoxib, celecoxib, etodolac, flurbiprofen, ibuprofen, ketoprofen, ketorolac, nabumetone, piroxicam, suprofen, tolmetin, zileuton, steroids, cyclooxygenase inhibitors, cortisone, hydrocortisone, betamethasone, dexamethasone, fluocortolone, prednisolone, phenylbutazone, triamcinolone, sulindac, indomethacin, salicylamide, naproxen, colchicine, fenoprofen, diclofenac, indoprofen, dexamethasone, allopurinol, oxyphenbutazone, probenecid and sodium salicylamide;

and

b) the muscle relaxant is present and is selected from the group consisting of alcuronium, alosetron, aminophylline, baclofen, carisoprodol, chlorphenesin, chlorphenesin carbamate, chlorzoxazone, chlormezanone, dantrolene, decamethonium, dyphylline, eperisione, ethaverine, gallamine triethiodide, hexafluorenium, metaxalone, metocurine iodide, orphenadrine, pancuronium, papaverine, pipecuronium, theophylline, tizanidine, tolperisone, tubocurarine, vecuronium, idrocilamide, ligustilide, cnidilide, senkyunolide, succinylcholine-chloride, danbrolene, cyclobenzaprine, methocarbamol, diazepam, mephenesin, methocarbomal, trihexylphenidyl, pridinol (pridinolum), and biperiden.

45. The device of claim 20, wherein the one or more coatings is present and is a drug-containing coating.

46. The device of claim 45, wherein the active agent is a first drug from a first therapeutic class and the drug-containing coating contains a different second drug from a different therapeutic class.

47. The device of claim 46, wherein the first drug and second drug are independently selected at each occurrence from the group consisting of central nervous system agent, drug that acts on α

-adrenergic receptors, electrolyte, ophthalmic agent, nutritional agent, antilipemic agent, phosphodiesterase inhibitor, β

-blocker, diuretic, sympathomimetic agent, anti-Dementia agent, anti-Alzheimer disease agent, anti-Parkinson disease agent, muscle relaxant, local anesthetic, anti-spasmodic, muscle contractant, tranquilizer, antihypertensive agent, hypnotic agent, sedative, antipsychotic agent, estrogen antagonist-agonist agent, steroid, antidiabetic agent, antidepressant agent, anticonvulsant agent, psychic energizer, anticoagulant agent, antiasthma agent, antihistamine agent, decongestant, analgesic agent, anti-inflammatory agent, antiviral agent, antiparasitic agent, antibacterial agent, cardiovascular agent, nutrient, hematological agent, endocrine agent, metabolic agent, renal agent, genitourinary agent, respiratory agent, gastrointestinal agent, anti-infective agent, biologic agent, immunological agent, dermatological agent, antineoplastic agent and diagnostic agent.

48. The device of claim 47, wherein

a) the anti-inflammatory drug is present and is selected from the group consisting of rofecoxib, celecoxib, etodolac, flurbiprofen, ibuprofen, ketoprofen, ketorolac, nabumetone, piroxicam, suprofen, tolmetin, zileuton, steroids, cyclooxygenase inhibitors, cortisone, hydrocortisone, betamethasone, dexamethasone, fluocortolone, prednisolone, phenylbutazone, triamcinolone, sulindac, indomethacin, salicylamide, naproxen, colchicine, fenoprofen, diclofenac, indoprofen, dexamethasone, allopurinol, oxyphenbutazone, probenecid and sodium salicylamide;

and

b) the muscle relaxant is present and is selected from the group consisting of alcuronium, alosetron, aminophylline, baclofen, carisoprodol, chlorphenesin, chlorphenesin carbamate, chlorzoxazone, chlormezanone, dantrolene, decamethonium, dyphylline, eperisione, ethaverine, gallamine triethiodide, hexafluorenium, metaxalone, metocurine iodide, orphenadrine, pancuronium, papaverine, pipecuronium, theophylline, tizanidine, tolperisone, tubocurarine, vecuronium, idrocilamide, ligustilide, cnidilide, senkyunolide, succinylcholine-chloride, danbrolene, cyclobenzaprine, methocarbamol, diazepam, mephenesin, methocarbomal, trihexylphenidyl, pridinol (pridinolum), and biperiden.

49. The device of claim 47, wherein the first drug is a muscle relaxant, and the second drug is an anti-inflammatory drug.

50. The device of claim 49, wherein the first drug is a carisoprodol and the second drug is diclofenac.

51. The device of claim 47, wherein

a) the first drug is a muscle relaxant and the second drug is a selective or specific COX-II inhibitor agent;

b) the first drug is an analgesic agent and the second drug is an anti-inflammatory agent, wherein the analgesic agent and the anti-inflammatory agent is 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 first and second agents are antihypertensive agents 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 first and second agents are antidiabetic agents;

e) the first drug is a decongestant and the second drug is an antihistamine;

f) the first drug and the second drug are anti-incontinence drugs;

g) the anti-incontinence drugs are selected from the group consisting of oxybutynin, tolterodine, and darifenacin;

h) the first drug is an antidepressant and the second drug is for the treatment of Dementia;

i) the first drug is an antidepressant and the second drug is an antianxiety drug;

j) the first drug is an antidepressant and the second drug is an antipsychotic drug;

k) the first drug is an antianxiety drug and the second drug is for the treatment of Dementia;

l) the first drug is an antianxiety drug and the second drug is an antipsychotic drug;

m) the first drug is an antianxiety drug and the second drug is an antimanic drug;

n) the first drug is an antipsychotic drug and the second drug is an antimanic drug;

o) the first drug and the second drug are for the treatment of Dementia;

p) the first drug is for the treatment of Dementia and the second drug is an antianxiety drug;

q) the first drug is an anticonvulsant drug and the second drug is an antianxiety drug;

r) the first drug is an anticonvulsant drug and the second drug is an antipsychotic drug;

s) the first drug is an anticonvulsant drug and the second drug is for the treatment of Dementia;

t) the first drug is anticonvulsant and the second drug is an antimanic drug;

u) the first drug is an antiparkinsonian drug and the second drug is an antidepressant;

v) the first drug is an antiparkinsonian drug and the second drug is for the treatment of

Dementia;

w) the first drug and the second drug are antiparkinsonian drugs;

x) the first drug and the second drug are mild CNS stimulants;

y) the first drug and the second drug are opioid analgesics;

z) the first drug is an opioid analgesic and the second drug is a non steroidal anti-inflammatory drug;

aa) the first drug and the second drug are non steroidal anti-inflammatory drugs;

bb) the first drug is a non steroidal anti-inflammatory drug and the second drug is a steroidal drug;

cc) the first drug and the second drug are antigout drugs;

or

dd) the first drug and the second drug are antilimepic drugs.

52. The device of claim 21, wherein the active agent is carisoprodol.

53. The device of claim 52 further comprising a second active agent in the core.

54. The device of claim 53, wherein the second active agent in the core is diclofenac.

55. The device of claim 54 further comprising an enteric coating.

56. The device of claim 52 further comprising a drug-containing coating.

57. The device of claim 56, wherein the drug-containing coating comprises diclofenac.

58. The device of claim 57 further comprising carisoprodol in the drug containing coating.

59. The device of claim 57 further comprising an enteric coating.

60. The device of claim 58 further comprising an enteric coating.

39. A method of preparing during use a coated controlled release device comprising a core comprising at least one active agent and, optionally, at least one excipient, a single or multi-layered wall enveloping the core, a preformed passageway in the wall, and a second passageway formed by breakage of a weakened section in the wall at a location spaced away from the preformed passageway due to an increase of internal pressure of the core during use, the method comprising the steps of:

a) providing a coated controlled release device comprising a core comprising;

at least one active agent and, optionally, at least one excipient, a single or multi-layered wall enveloping the core, wherein at least one of the layers of the wall retains its physical integrity during release of active agent from the core of the device, a weakened section in the wall, and a preformed passageway through at least one layer of the wall, wherein the layer of the wall that comprises the preformed passageway is adapted to rupture and form the second passageway during use of the device; and

b) exposing the device to an environment of use in which fluid is absorbed into the device thereby increasing the internal osmotic pressure within the device and causing breakage of the weakened section in the wall to form the second passageway at a location spaced away from the preformed passageway.

40. A method for treating a symptom, disorder and/or disease with at least one active agent, the method comprising the steps of:

a) providing at least one coated controlled release device comprising a core that comprises at least one active agent and, optionally, at least one excipient and that is substantially enclosed within a wall comprising a preformed passageway and a weakened section in the wall, wherein the weakened section of the wall is adapted to rupture during use of the device to form a second passageway at a region spaced away from the preformed passageway; and

b) administering the device to a subject in need of such treatment such that the at least one active agent is released for a first period of time through the preformed passageway and then, after formation of the second passageway formed by tearing of the wall due to an increase of internal pressure of the core during use, the at least one active agent is released for a second period of time through one or both passageways.