MULTIPARTICULATE OSMOTIC DELIVERY SYSTEM

• US 20090004281A1
• Filed: 06/26/2007
• Published: 01/01/2009
• Est. Priority Date: 06/26/2007
• Status: Abandoned Application

• Current Assignee: Chantilly Biopharma, LLC
• Original Assignee: Biovail Laboratories International Srl (Bausch Health Cos., Inc.)
• Inventors: JACKSON, Graham, Nghiem, Tien
• Application Number:
  US11/768,764
• Publication Number:
  US 20090004281A1
• Time in Patent Office: Days
• US Class Current: 424/490
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/554 having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 9/06 Antiarrhythmics

Abstract

The present invention relates to a multiparticulate osmotic delivery system. The system is a modified release composition suitable for oral administration. The composition includes a core that includes at least one drug in combination with at least one pharmaceutically acceptable excipient. The composition further includes an osmotic subcoat surrounding the core, and a modified release overcoat surrounding the osmotic subcoated core.

Claims

1. A pharmaceutical composition, comprising:

at least one microparticle comprising at least one core which is at least partially coated with at least one osmotic subcoat, and at least one outer coat which at least partially coats the at least one osmotic subcoat,

wherein

said at least one core comprises at least one drug, and at least one excipient, and

said at least one osmotic subcoat comprises at least one osmotic agent and at least one osmotic deposition vehicle.

2. The composition of claim 1, wherein the at least one drug is selected from the group consisting of bupropion, carvedilol, citalopram, diltiazem, fluoxetine, metroprolol, pramipexole, quetiapine, ramipril, rivastigmine, rosiglitazone, sumatriptan, topiramate, tramadol, venlafaxine, zolpidem, memantine, dexmethylphenidate, dimebon, salts of these drugs, and combinations thereof.

3. The composition of claim 1, wherein the at least one drug is dexmethylphenidate or its salt.

4. The composition of claim 1, wherein the at least one drug is rivastigmine or its salt.

5. The composition of claim 1, wherein the at least one drug is pramipexole or its salt.

6. The composition of claim 1, wherein the at least one drug is diltiazem or its salt.

7. The composition of claim 1, wherein the at least one drug is tramadol or its salt.

8. The composition of claim 1, wherein the at least one drug is bupropion hydrochloride.

9. The composition of claim 1, wherein the at least one drug is a member of a drug class selected from the group consisting of ace-inhibitors, alkaloids, anabolic agents, analgesics, antacids, anti-allergy agents, anti-Alzheimer'"'"'s Disease agents, anti-anginal drugs, antianxiety agents, anti-arrhythmia agents, antiasthmatics, antibacterial agents, anti-bipolar agents, antifungal agents, antibiotics, anticholesterolemics, anticlotting agents, anticonvulsants, anticoagulants, antidepressants, antidiarrheal preparations, anti-emetics, antihistamines, antihyperglycemic agents, antihypertensives, anti-impotence agents, anti-infectives, anti-inflammatories, antilipid agents, antimanics, anti-migraine agents, antinauseants, antineoplastics, antiobesity agents, antiparasitics, anti-Parkinsonism agents, antipsychotics, antipyretics, antispasmodics, antistroke agents, antithrombotics, antithyroid preparations, antitumor agents, antitussives, antiulcer agents, anti-uricemic agents, antiviral agents, anxiolytic agents, appetite stimulants, appetite suppressants, autoimmune disorders agents, barbiturates, beta-blocking agents, blood glucose-lowering agents, bronchodilators, cardiovascular agents, cerebral dilators, chelating agents, cholecystekinin antagonists, chemotherapeutic agents, cholesterol-reducing agents, cognition activators, cognitive enhancers, contraceptives, coronary dilators, cough suppressants, decongestants, deodorants, dermatological agents, diabetes agents, diuretics, emollients, enzymes, erythropoietic drugs, expectorants, fertility agents, fungicides, gastrointestinal agents, growth regulators, anti-headache agents, anti-cluster headache agents, hormone replacement agents, hyperglycemic agents, hypnotic agents, hypoglycemic agents, ion-exchange resins, laxatives, migraine treatments, mineral supplements, mucolytics, narcotics, neuroleptics, neuromuscular drugs, non-steroidal anti-inflammatories (NSAIDs), nutritional additives, peripheral vasodilators, polypeptides, prostaglandins, psychotropics, renin inhibitors, respiratory stimulants, anti-restless leg syndrome agents, sedatives, steroids, stimulants, sympatholytics, thyroid preparations, tranquilizers, uterine relaxants, vaginal preparations, vasoconstrictors, vasodilators, vertigo agents, vitamins, wound healing agents, and combinations thereof.

10. The composition of claim 9, comprising at least one drug selected from the group consisting of anti-Alzheimer'"'"'s Disease agents.

11. The composition of claim 9, comprising at least one drug selected from the group consisting of anti-arrhythmia agents.

12. The composition of claim 9, comprising at least one drug selected from the group consisting of anti-Parkinsonism agents.

13. The composition of claim 9, comprising at least one drug selected from the group consisting of anti-restless leg syndrome agents.

14. The composition of claim 9, comprising at least one drug selected from the group consisting of anti-cluster headache agents.

15. The composition of claim 9, comprising at least one drug selected from the group consisting of anti-bipolar agents.

16. The composition of claim 9, comprising at least one drug selected from the group consisting of antihypertensives.

17. The composition of claim 9, comprising at least one drug selected from the group consisting of analgesics.

18. The composition of claim 1, wherein the at least one drug is selected from the group consisting of acetazolamide, acetaminophen, acetic acid, acetohexamide, acetylsalicylic acid, buffered acetylsalicylic acid;

acrivastine, acyclovir, albuterol, albuterol sulfate, alcohol, alfaxalone, alkaline phosphatase, allantoin, aloe, alprostadil, aluminum acetate, aluminum carbonate, aluminum chlorohydrate, aluminum hydroxide, alprozolam, amino acids, aminobenzoic acid, amlodipine besylate, amoxicillin, ampicillin, amsacrine, amsalog, anethole, apomorphine, ascorbic acid, aspartame, aspirin, astemizole, atenolol, atorvastatin calcium, azatidine, azatidine maleate, azithromycin, bacitracin, balsam peru, BCNU (carmustine), becampicillin hydrochloride, beclomethasone diproprionate, benzalkonium chloride, benzocaine, benzoic acid, benzophenones, benzoyl peroxide, benzquinamide, benzquinamide hydrochloride, betamethasone, bethanechol, biotin, bisacodyl, bismuth subsalicylate, bomyl acetate, bromopheniramine, bromopheniramine maleate, bupropion hydrochloride, buspirone, caffeine, calamine, calcium carbonate, calcium casinate, calcium hydroxide, camphor, captopril, carbenicillin indanyl sodium, carvedilol, cascara sagrada, castor oil, cefaclor, cefadroxil, celicoxib, cephalexin, centrizine, centrizine hydrochloride, cetirizine, cetyl alcohol, cetylpyridinium chloride, chelated minerals, chlorambucil, chloramphenicol, chlorcyclizine hydrochloride, chlordiazepoxide, chlorhexidine gluconate, chloroxylenol, chloropentostatin, chlorpheniramine, chlorpheniramine maleate, chlorpheniramine tannate, chlorpromazine, chlorpropamide, chlorthalidone, chlorzolamide, cholestyramine resin, choline bitartrate, chondrogenic stimulating protein, cimetidine, cimetidine hydrochloride, cinnamedrine hydrochloride, cinnarizine, cisapride, citalopram, citric acid, clarithromycin, clemastine, clemastine flumarate, clonidine, clonidine hydrochloride, clorfibrate, cocoa butter, cod liver oil, codeine, codeine fumarate, codeine phosphate, cortisone acetate;

cotrimoxazole, ciprofloxacin HCl, cyanocobalamin, cyclizine hydrochloride, cyproheptadine, cyproheptadine hydrochloride, dexmethylphenidate, danthron, dexbromopheniramine maleate, dextromethorphan, dextromethorphan hydrohalide, diazepam, dibucaine, dichloralphenazone, diclofen, alkali metal salts of diclofen, diclofenac sodium, dicumarol, digitoxin, digoxin, dihydroergotamine, hydrogenates of dihydroergotamine, mesylates of dihydroergotamine, diltiazem, dimebon, dimenhydrinate, dimethicone, dioxybenzone, diphenhydramine, diphenhydramine citrate, diphenhydramine hydrochloride, divalproex, alkali metal salts of divalproex, docusate calcium, docusate potassium, docusate sodium, donepezil, doxazosin, doxepin, doxepin hydrochloride, doxycycline hydrate, doxylamine succinate, dronabinol, echinomycin, econazole, efaroxan, enalapril, enalaprilic acid, enoxacin, ephedrine, epinephrine bitartrate, ergotamine, ergotamine tartrate, erythromycin, erythropoietin, estropipate, ethinyl estradiol, etomidate, eucalyptol, famotidine, fenoprofen, metal salts of fenoprofen, ferrous fumarate, ferrous gluconate, ferrous sulfate, fluconazole, fluoxetine, fluoxymesterone, folic acid, fosphenytoin, 5-fluorouracil (5-FU), fluoxetine, fluoxetine hydrochloride, flurbiprofen, fluspirilene, furosemide, gabapentan, gentamicin, gemfibrozil, glipizide, glycerine, glyceryl stearate, granisetron, granisetron hydrochloride, griseofulvin, guafenesin, hexylresorcinol, hydrochlorothiazide, hydrocodone, tartrates of hydrocodone, hydrocortisone, hydrocortisone acetate, 8-hydroxyquinoline sulfate, hydroxyzine, hydroxyzine pamoate, hydrochloride salts of hydroxyzine, ibuprofen, indomethacin, inositol, insulin, iodine, ipecac, iron, iroxicam, isosorbide, monoand dinitrates of isosorbide, isoxicam, kaolin, ketamine, ketanserin, ketoprofen, lactic acid, lanolin, L-DOPA, lecithin, leuprolide acetate, levocabastine, lidocaine, lidocaine hydrochloride, lifinopril, liotrix, lisinopril, lomustine, loperamide, loratadine, lovastatin, magnesium carbonate, magnesium hydroxide, magnesium salicylate, magnesium trisilicate, meclizine, meclizine hydrochloride, mefenamic acid, meclofenamic acid, meclofenamate sodium, medroxyprogesterone acetate, meloxicam, memantine, methenamine mandelate, menthol, meperidine hydrochloride, metaproterenol sulfate, methanstenolone, methscopolamine, nitrates of methscopolamine, methsergide, methsergide maleate, methyl nicotinate, methyl salicylate, methyl cellulose, methsuximide, 17-methyltestosterone, metoclopramide, halides of metoclopramide, hydrates of metoclopramide, metronidazole, metronidazole hydrochloride, metoprolol, metoprotol tartrate, mianserin, miconazole nitrate, mineral oil, minocycline, minoxidil, mioflazine, morphine, nadolol, naproxen, sodium salts of naproxen, alkali metal salts of naproxen, nifedipine, neomycin sulfate, niacin, niacinamide, nicotine, nicotinamide;

nimesulide;

nitroglycerine;

nonoxynol-9;

norethindrone and its acetate;

nystatin, octoxynol, octoxynol-9, octyl dimethyl PABA, octyl methoxycinnamate, omega-3 polyunsaturated fatty acids, omeprazole, ondansetron, ondansetron hydrochloride, oxfendazole, oxolinic acid, oxybenzone, oxtriphylline, para-aminobenzoic acid (PABA), padimate-O, paramethadione, paroxetine, penfluridole, penicillin G, pentastatin, peppermint oil, pentaerythritol tetranitrate, pentobarbital sodium, perphenazine, phenelzine sulfate, phenindamine, phenindamine tartrate, pheniramine maleate, phenobarbital, phenol, phenolphthalein, phenylephrine, tannates of phenylephrine, hydrochlorides of phenylephrine, phenylpropanolamine, phenylpropanolamine hydrochloride, phenyloin, pirmenol, piroxicam, salts of piroxicam, polymicin B sulfate, potassium chloride, potassium nitrate, pramipexole, pramiracetin, pramoxine, pramoxine hydrochloride, prazepam, prazosin, prednisolone, procainamide hydrochloride, procaterol, promethazine, promethazine hydrochloride, propoxyphene, propoxyphene hydrochloride, napsylate, prochlorperazine, prochlorperazine maleate, propanolol, propanolol hydrochloride, promethazine, promethazine hydrochloride, propanolol, prostacyclin, pseudoephedrine, sulfates of pseudoephedrine, hydrochlorides of pseudoephedrine, pyridoxine, pyrolamine, hydrochlorides of pyrolamine, tannates of pyrolamine, quetiapine, quinapril, quinidine gluconate, quinidine sulfate, quinestrol, ralitoline, ramipril, ranitidine, resorcinol, retinol, riboflavin, rivastigmine, rosiglitazone, salicylic acid, scopolamine, sertraline, sesame oil, shark liver oil, sildenafil citrate, simethicone, sodium bicarbonate, sodium citrate, sodium fluoride, sodium monofluorophosphate, spiramycin, spironolactone, sucralfate, sulfanethoxazole, sulfasalazine, sulfur, sulpiride, sumatriptan, sumatriptan succinate, tacrine, tacrine hydrochloride, terconazole, terfenadine, testosterone, tetracycline, tetracycline hydrochloride, tetrahydroaminoacridine, theophylline, thiabendazole, thiethylperazine, thiethylperazine maleate, thioperidone, thiothixene hydrochloride, timolol, timolol maleate, tolmetin, tolnaftate, topiramate, tramadol, tretinoin, triazolam, trimetrexate, trimazosin, triclosan, trimethobenzamide, trimethobenzamide hydrochloride, tripelennamine, tripelennamine hydrochloride, tripolidine hydrochloride, troleandomycin, tubulazole, undecylenic acid, valdecoxib, vancomycin, venlafaxine, verapamil HCl, vidaribine phosphate, virazole, vitamin A, vitamin C, vitamin D, vitamin B1, vitamin B2, vitamin B3, vitamin B4, vitamin B5, vitamin B6, vitamin B7, vitamin B9, vitamin B12, vitamin E, vitamin K, witch hazel, xylometazoline hydrochloride, zinc, zinc sulfate, zinc undecylenate, ziprasidone, zolpidem, salts thereof, and combinations thereof.

19. The composition of claim 1, wherein the at least one drug is in a salt form.

20. The composition of claim 1, wherein the at least one drug is an enantiomer.

21. The composition of claim 1, wherein the at least one drug is a mixture of enantiomers.

22. The composition of claim 1, wherein the at least one drug is a diastereomer.

23. The composition of claim 1, wherein the at least one drug is a prodrug.

24. The composition of claim 1, wherein the shape of the at least one microparticle is spherical.

25. The composition of claim 1, wherein the at least one microparticle is pearl shaped.

26. The composition of claim 1, wherein, in the at least one core, the at least one drug is enveloped by the at least one excipient.

27. The composition of claim 1, wherein, in the at least one core, the at least one drug is dispersed in a matrix with the at least one excipient.

28. The composition of claim 27, wherein the matrix is an immediate release matrix.

29. The composition of claim 27, wherein the matrix is a modified release matrix.

30. The composition of claim 1, wherein the at least one osmotic subcoat fully surrounds the at least one core.

31. The composition of claim 1, wherein the at least one outer coat fully surrounds the at least one osmotic subcoat.

32. The composition of claim 1, wherein the at least one osmotic subcoat fully surrounds the at least one core, and wherein the at least one outer coat fully surrounds the at least one osmotic subcoat.

33. The composition of claim 1, wherein the at least one drug has a solubility such that ≦

about 10 parts water will dissolve one part of the drug, so long as the total amount of water to dissolve the at least one drug is not 0 parts.

34. The composition of claim 1, wherein the at least one drug has a solubility such that ≧

30 parts of water will dissolve one part of the drug.

35. The composition of claim 1, wherein the at least one drug has a solubility such that from more than about 10 parts water to less than about 30 parts water will dissolve one part of the drug.

36. The composition of claim 1, wherein the total amount of the at least one drug present in the composition ranges from about 200 mg to about 10,000 mg.

37. The composition of claim 1, wherein the total amount of the at least one drug present in the composition ranges from more than about 20 mg to less than about 200 mg.

38. The composition of claim 1, wherein the total amount of the at least one drug present in the composition ranges from less than about 20 mg to greater than 0 mg.

39. The composition of claim 1, wherein the at least one microparticle has a diameter ranging from about 50 μ

m to about 800 μ

m.

40. The composition of claim 1, wherein the at least one drug is present in a positive amount of ≦

20 mg, wherein at least 30 parts of water is used to dissolve 1 part of the drug, and wherein ≧

90% of the drug is released from the composition within 24 hours of placing the composition into an external environment of use,

wherein the external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

41. The composition of claim 1, wherein the drug is present in a positive amount of ≦

20 mg, and wherein ≧

90% of the drug is released from the composition within 24 hours of placing the composition into an external environment of use,

wherein the external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

42. The composition of claim 41,

wherein the at least one drug is pramipexole,

wherein the volume of the dissolution medium is 500 ml,

wherein the dissolution medium is stirred at 50 rotations per minute, and

wherein the dissolution medium is the phosphate buffer having a pH of 6.8.

43. The composition of claim 41,

wherein the at least one drug is rivastigmine,

wherein the volume of the dissolution medium is 500 ml,

wherein the dissolution medium is stirred at 50 rotations per minute, and

wherein the dissolution medium is the 0.1N HCl aqueous solution.

44. The composition of claim 41,

wherein the at least one drug is rivastigmine,

wherein the volume of the dissolution medium is 500 ml,

wherein the dissolution medium is stirred at 50 rotations per minute, and

wherein the dissolution medium is the acetate buffer having a pH of 4.5.

45. The composition of claim 41,

wherein the at least one drug is rivastigmine,

wherein the volume of the dissolution medium is 500 ml,

wherein the dissolution medium is stirred at 50 rotations per minute, and

wherein the dissolution medium is the phosphate buffer having a pH of 6.8.

46. The composition of claim 1,

wherein the at least one drug is present in a positive amount of ≦

20 mg,

wherein there is increased release of the at least one drug from the composition within 24 hours of placing the composition into a first external environment of use compared to an otherwise identical or similar second composition comprising the at least one drug but not containing an osmotic subcoat placed into a second external environment of use,

wherein the first external environment of use and the second external environment of use are identical or similar, and

wherein each external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

47. The composition of claim 1, wherein at least thirty parts of water is used to dissolve one part of the drug, and wherein ≧

90% of the drug is released from the composition within 24 hours of placing the composition into an external environment of use,

wherein the external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

48. The composition of claim 1, wherein at least thirty parts of water is required to dissolve one part of the drug, wherein there is increased release of the at least one drug from the composition within 24 hours of placing the composition into a first external environment of use compared to an otherwise identical or similar composition comprising the at least one drug but not containing an osmotic subcoat placed into a second external environment of use,

wherein the first external environment of use and the second external environment of use are identical or similar, and,

wherein each external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

49. The composition of claim 1, wherein the at least one core comprises from about 0.1% by weight to about 99.9% by weight of the at least one excipient and from about 0.1% by weight to about 99.9% by weight of the at least one drug.

50. The composition of claim 1, wherein the at least one osmotic subcoat comprises from about 1% by weight to about 99% by weight of the at least one osmotic deposition vehicle and from about 1% by weight to about 99% by weight of the at least one osmotic agent.

51. The composition of claim 1, wherein the weight of the least one outer coat is equal to from about 1% to about 99% of the weight of the at least one core.

52. The composition of claim 49, wherein the total weight of the at least one core is the weight of the at least one drug plus the weight of the at least one excipient.

53. The composition of claim 50, wherein the total weight of the at least one osmotic subcoat is the weight of the at least one osmotic agent plus the weight of the at least one osmotic deposition vehicle.

54. The composition of claim 1, wherein the at least one core comprises 97.5% by weight of the at least one excipient and 2.5% by weight of the at least one drug, and wherein the total % by weight of the at least one drug and the at least one excipient is 100% of the weight total of the at least one core.

55. The composition of claim 54, wherein the at least one drug is pramipexole and wherein the at least one excipient is glyceryl monostearate.

56. The composition of claim 1, wherein the at least one core comprises 40% by weight of the at least one excipient and 60% by weight of the at least one drug and wherein the total % by weight of the at least one drug and the at least one excipient is 100% of the weight total of the at least one core.

57. The composition of claim 56, wherein the at least one drug is diltiazem and wherein the at least one excipient is glyceryl monostearate.

58. The composition of claim 1, wherein the at least one core comprises 90% by weight of the at least one excipient and 10% by weight of the at least one drug and wherein the total % by weight of the at least one drug and the at least one excipient is 100% of the weight total of the at least one core.

59. The composition of claim 58, wherein the at least one drug is rivastigmine and the at least one excipient is glyceryl monostearate.

60. The composition of claim 1, wherein the at least one excipient is selected from the group consisting of a spheronization aid, a solubility enhancer, a disintegrating agent, a diluent, a lubricant, a binder, a filler, a suspending agent, an emulsifying agent, an anti-foaming agent, a falvouring agent, a colouring agent, a chemical stabilizer, a pH modifier, a swelling agent, and mixtures thereof.

61. The composition of claim 60, wherein the at least one excipient comprises a spheronization aid, and wherein the spheronization aid is selected from the group consisting of a distilled monoglyceride, a hydrogenated oil, a fatty acid salt, a polyol, a polyoxyethylene ether, an esterified polyoxyethylene, a wax, a wax like material, a thermo-plastic polymer, a thermo-softening polymer, and combinations thereof.

62. The composition of claim 61, wherein the spheronization aid is selected from the group consisting of glyceryl monostearate, glyceryl behenate, glyceryl dibehenate, glyceryl palmitostearate, hydrogenated castor oil, magnesium stearate, calcium stearate, mannitol, sorbitol, xylitol, stearic acid, palmitic acid, sodium lauryl sulfate, PEG-32 distearate, PEG-150 distearate, cetostearyl alcohol, carnauba wax, white wax, paraffin wax, povidone, a cellulose ether, a polyvinylalcohol, and combinations thereof.

63. The composition of claim 62, wherein the spheronization aid comprises glyceryl monostearate.

64. The composition of claim 62, wherein the spheronization aid comprises glyceryl behenate.

65. The composition of claim 62, wherein the spheronization aid comprises glyceryl palmitostearate.

66. The composition of claim 60, wherein the at least one excipient comprises a filler, and wherein the filler is selected from the group consisting of calcium phosphate dibasic, tricalcium phosphate, calcium carbonate, a starch, a modified starch, microcrystalline cellulose, sucrose, dextrose, a maltodextrin, lactose, fructose, and combinations thereof.

67. The composition of claim 66, wherein the filler comprises microcrystalline cellulose.

68. The composition of claim 66, wherein the filler comprises lactose.

69. The composition of claim 60, wherein the at least one excipient comprises a solubility enhancer, and wherein the solubility enhancer is selected from the group consisting of a macrogol fatty acid ester, a polyethylene glycol, a polyethylene-polypropylene glycol, sorbitol, a propylene glycol, a pentaerythritol, and mixtures thereof.

70. The composition of claim 69, wherein the at least one excipient comprises at least one polyethylene-polypropylene glycol, and wherein the average molecular weight of the polyethylene-propylene glycol ranges from 9,480-14,600.

71. The composition of claim 69, wherein the at least one excipient comprises at least one polyethylene glycol, and wherein the average molecular weight of the polyethylene glycol ranges from 3,000-4,800.

72. The composition of claim 69, wherein the at least one excipient comprises at least one macrogel fatty acid ester, wherein the melting point of the macrogel fatty acid ester ranges from 40°

C. to 60°

C., and wherein the hydrophilic-lipophilic balance value of the macrogel fatty acid ester is 13.

73. The composition of claim 60, wherein the at least one excipient comprises a binder, and wherein the binder is selected from the group consisting of polyethylene glycol, stearic acid, a low melting point wax, and mixtures thereof.

74. The composition of claim 1, wherein the at least one osmotic agent is selected from the group consisting of sodium chloride, sodium bromide, sodium bisulfate, potassium acid tartrate, citric acid, sodium citrate, fumaric acid, mannitol, sucrose, and mixtures thereof.

75. The composition of claim 74, wherein the at least one osmotic agent comprises sodium chloride.

76. The composition of claim 74, wherein the at least one osmotic agent comprises sodium citrate.

77. The composition of claim 74, wherein the at least one osmotic agent comprises fumaric acid.

78. The composition of claim 74, wherein the at least one osmotic agent comprises mannitol.

79. The composition of claim 1, wherein said at least one osmotic deposition vehicle is selected from the group consisting of a polyvinyl pyrrolidone, a hydroxyethyl cellulose, a hydroxypropyl cellulose, a low molecular weight hydroxypropyl methylcellulose (HPMC), a polymethacrylate, an ethyl cellulose and mixtures thereof.

80. The composition of claim 79, wherein the at least one osmotic deposition vehicle comprises a low molecular weight hydroxypropyl methylcellulose (HPMC).

81. The composition of claim 79, wherein the at least one osmotic deposition vehicle comprises hypromellose substitution type 2910 with a nominal viscosity of 6 cP.

82. The composition of claim 79, wherein the at least one osmotic deposition vehicle comprises hypromellose substitution type 2906 with a nominal viscosity of 3 cP.

83. The composition of claim 79, wherein the at least one osmotic deposition vehicle comprises polyvinylpyrrolidone with a molecular weight of 30,000.

84. The composition of claim 1, wherein said at least one microparticle is partially coated with the at least one outer coat.

85. The composition of claim 1, wherein the at least one core is partially coated with the at least one osmotic subcoat.

86. The composition of claim 1, wherein the at least one outer coat comprises at least one polymer, polymeric material, or polymeric dispersion.

87. The composition of claim 86, wherein the at least one polymer, polymeric material, or polymeric dispersion is selected from the group consisting of a poly (meth)acrylate neutral copolymer aqueous dispersion, a (meth)acrylate neutral copolymer, a polyvinyl acetate aqueous dispersion, a polyvinyl acetate, an ethylcellulose, an ethylcellulose aqueous dispersion, a dispersion of a poly(ethyl acrylate and methyl acrylate), a poly(ethyl acrylate and methyl acrylate) and combinations thereof.

88. The composition of claim 87, wherein the at least one polymer, polymeric material, or polymeric dispersion comprises a poly(meth)acrylate neutral copolymer.

89. The composition of claim 87, wherein the at least one polymer, polymeric material, or polymeric dispersion comprises a polyvinyl acetate.

90. The composition of claim 87, wherein the at least one polymer, polymeric material, or polymeric dispersion comprises an ethylcellulose.

91. The composition of claim 87, wherein the at least one polymer, polymeric material, or polymeric dispersion comprises a poly(ethyl acrylate and methyl acrylate).

92. The composition of claim 1, wherein the at least one outer coat comprises at least one glidant.

93. The composition of claim 92, wherein the at least one glidant is selected from the group consisting of talc, magnesium stearate, calcium silicate, glyceryl monostearate, and combinations thereof.

94. The composition of claim 93, wherein the at least one glidant comprises talc.

95. The composition of claim 93, wherein the at least one glidant comprises glyceryl monostearate.

96. The composition of claim 93, wherein the at least one glidant comprises calcium silicate.

97. The composition of claim 93, wherein the at least one glidant comprises glyceryl monostearate.

98. The composition of claim 1, wherein the at least one outer coat comprises at least one emulsifier.

99. The composition of claim 98, wherein the at least one emulsifier comprises polyoxethylene sorbitan monooleate.

100. The composition of claim 1, wherein the outer coat comprises at least one anti-foaming agent.

101. The composition of claim 100, wherein the at least one anti-foaming agent comprises simethicone.

102. The composition of claim 1, wherein the outer coat comprises at least one plasticizer.

103. The composition of claim 102, wherein the plasticizer is selected from the group consisting of acetyltributyl citrate, triacetin, dibutyl sebacate, and mixtures thereof.

104. The composition of claim 103, wherein the plasticizer comprises acetyltributyl citrate.

105. The composition of claim 103, wherein the plasticizer comprises triacetin.

106. The composition of claim 103, wherein the plasticizer comprises dibutyl sebacate.

107. The composition of claim 1, wherein the outer coat does not comprise a pore former.

108. The composition of claim 1, wherein the at least one drug is present in a positive amount of ≦

20 mg, wherein ≧

90% of the drug is released from the composition within 24 hours of placing the composition into an external environment of use, wherein the at least one outer coat does not comprise a pore former,

wherein the external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

109. The composition of claim 1, wherein the at least one outer coat does not comprise a pore former, wherein the at least one drug is present in a positive amount of ≦

20 mg, wherein there is increased release of the at least one drug from the composition within 24 hours of placing the composition into a first external environment of use compared to an otherwise identical or similar second composition comprising the at least one drug but not containing an osmotic subcoat placed into a second external environment of use,

wherein the first external environment of use and the second external environment of use are identical or similar, and

wherein each external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

110. The composition of claim 1, wherein at least 30 parts of water is required to dissolve one part of the drug, wherein ≧

90% of the drug is released from the composition within 24 hours of placing the composition into an external environment of use, wherein the at least one outer coat does not comprise a pore former, and

wherein the external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

111. The composition of claim 1, wherein at least 30 parts of water is required to dissolve one part of the drug, wherein the at least one outer coat does not comprise a pore former, wherein there is increased release of the at least one drug from the composition within 24 hours of placing the composition into a first external environment of use compared to an otherwise identical or similar second composition comprising the at least one drug but not containing an osmotic subcoat placed into a second external environment of use,

wherein the first external environment of use and the second external environment of use are identical or similar, and

wherein each external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

112. The composition of claim 1, wherein the at least one outer coat comprises a pore former.

113. The composition of claim 112, wherein the pore former comprises at least one material selected from the group consisting of hypromellose substitution type 2910 having a viscosity ranging from 5 cP to 7 cP, hypromellose substitution type 2906 having a viscosity ranging from 2 cP to 4 cP, a polyvinylpyrrolidione having a molecular weight ranging from 20,000 to 40,000, and mixtures thereof.

114. The composition of claim 1, wherein the at least one outer coat comprises at least one drug, and wherein the at least one drug of the at least one outer coat may be the same or different from the drug in the core.

115. The composition of claim 1, wherein the composition is an extended release composition.

116. The composition of claim 1, wherein the composition is a delayed release composition.

117. The composition of claim 116, wherein the composition, when placed into an external environment of use, provides a drug release profile wherein a predetermined lag time is substantially independent of the pH of the external environment of use,

wherein the external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

118. The composition of claim 1, wherein the composition is a sustained release composition.

119. The composition of claim 1, wherein the composition, when placed into an external environment of use, provides a drug release profile that does not include a lag time,

wherein the external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

120. The composition of claim 1, wherein the at least one outer coat does not comprise a seal coat.

121. The composition of claim 1, wherein the at least one osmotic agent and the at least one osmotic deposition vehicle are present in the at least one osmotic subcoat in amounts sufficient to achieve an osmotic pressure gradient across the at least one outer coat for the transport of a solvent or aqueous fluid from an external environment of use into said core, and transport of said drug from said core to said external environment of use,

wherein the external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

122. The composition of claim 121, wherein the release of the drug from the core to the external environment of use is effected by both the osmotic pressure gradient and passive diffusion.

123. The composition of claim 1, wherein the at least one osmotic deposition vehicle does not effect the rate and/or extent of release of the at least one drug.

146. The composition of claim 1, wherein the drug is present in an amount of more than about 200 mg, and wherein ≧

90% of the drug is released from the composition within 24 hours of placing the composition into an external environment of use,

wherein the external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

147. The composition of claim 146,

wherein the at least one drug is diltiazem,

wherein the volume of the dissolution medium is 900 ml,

wherein the dissolution medium is stirred at 100 rotations per minute, and

wherein the dissolution medium is water.

124. A method of administering at least one drug, the method comprising:

administering to a subject in need thereof a pharmaceutical composition, comprising;

at least one microparticle comprising at least one core which is at least partially coated with at least one osmotic subcoat, and at least one outer coat which at least partially coats the at least one osmotic subcoat,

wherein

said at least one core comprises at least one drug, and at least one excipient, and

said at least one osmotic subcoat comprises at least one osmotic agent and at least one osmotic deposition vehicle.

125. The method of claim 124, wherein the composition is in the form of a tablet.

126. The method of claim 124, wherein the composition is in the form of a capsule.

127. The method of claim 124, wherein the composition is administered with a dose sipping technology.

128. The method of claim 124, wherein the composition is in the form of an orally disintegrating tablet.

129. A method of treating a disease in a subject in need thereof, said method comprising:

administering to a subject in need thereof an effective amount of a pharmaceutical composition, said pharmaceutical composition comprising;

at least one microparticle comprising at least one core which is at least partially coated with at least one osmotic subcoat, and at least one outer coat which at least partially coats the at least one osmotic subcoat,

wherein

said at least one core comprises at least one drug, and at least one excipient, and

said at least one osmotic subcoat comprises at least one osmotic agent and at least one osmotic deposition vehicle

said at least one drug is effective for treating said disease in the subject in need thereof.

130. A method of making a pharmaceutical composition, said pharmaceutical composition comprising:

at least one microparticle comprising at least one core which is at least partially coated with at least one osmotic subcoat, and at least one outer coat which at least partially coats the at least one osmotic subcoat,

wherein

said at least one core comprises at least one drug, and at least one excipient, and

said at least one osmotic subcoat comprises at least one osmotic agent and at least one osmotic deposition vehicle,

wherein said method comprises

(1) forming the at least one core which comprises said at least one drug and at least said one excipient;

(2) coating, at least partially, said at least one core with said at least one osmotic subcoat, and

(3) coating, at least partially, said at least one osmotic subcoat with said at least one outer coat.

131. The method of claim 130, wherein the at least one osmotic subcoat fully surrounds the at least one core, and wherein the at least one outer coat fully surrounds the at least one osmotic subcoat.

132. The method of claim 130, wherein said at least one outer coat does not contain a pore former.

133. A pharmaceutical composition, which is prepared by a method comprising:

(1) forming at least one core which comprises at least one drug and at least one excipient;

(2) coating, at least partially, said at least one core with at least one osmotic subcoat, and

(3) coating, at least partially, said at least one osmotic subcoat with at least one outer coat.

134. The composition of claim 133, wherein the at least one osmotic subcoat fully surrounds the at least one core, and wherein the at least one outer coat fully surrounds the at least one osmotic subcoat.

135. The composition of claim 133, wherein the at least one outer coat does not comprise a pore former.

136. A method of controlling the rate and/or extent of release of at least one drug from the core of a microparticle comprising at least one core into an external environment of use which is at least partially coated with at least one osmotic subcoat, and at least one outer coat at least partially coats the at least one osmotic subcoat, wherein

said at least one core comprises at least one drug and at least one excipient,

said at least one osmotic subcoat comprises at least one osmotic agent and at least one osmotic deposition vehicle,

the method comprising

controlling the thickness of the at least one outer coat, thereby controlling the release rate of the at least one drug from the core of the microparticle into the external environment of use,

wherein the external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

137. The method of claim 136, wherein the at least one outer coat comprises a stable monolithic coating comprising an aqueous dispersion of a neutral ester copolymer without any functional groups, a poly glycol having a melting point greater than 55°

C., and at least one pharmaceutically acceptable excipient.

138. The method of claim 136, wherein the at least one outer coat comprises a water insoluble, water permeable polymer, a water soluble polymer, and a plasticizer.

139. The method of claim 136, wherein the at least one osmotic subcoat fully surrounds the at least one core, and wherein the at least one outer coat fully surrounds the at least one osmotic subcoat.

140. The method of claim 136, wherein the at least one outer coat does not comprise a pore former.

141. A pharmaceutical composition, comprising

at least one core which is at least partially coated with at least one osmotic subcoat,

at least one outer coat which at least partially coats the at least one osmotic subcoat,

wherein the at least one core comprises at least one drug and at least one excipient,

wherein the at least one osmotic subcoat comprises at least one osmotic agent and at least one osmotic deposition vehicle, and

a means for releasing the at least one drug from the composition.

142. The composition of claim 141, wherein the at least one osmotic subcoat fully surrounds the at least one core, and wherein the at least one outer coat fully surrounds the at least one osmotic subcoat.

143. The composition of claim 141, wherein the at least one outer coat does not comprise a pore former.

144. A method for controlling the rate and/or extent of release of at least one drug from a composition, into an external environment of use, the composition comprising

at least one microparticle comprising at least one core which is at least partially coated with at least one osmotic subcoat, and at least one outer coat which at least partially coats the at least one osmotic subcoat,

wherein

said at least one core comprises at least one drug, and at least one excipient, and

said at least one osmotic subcoat comprises at least one osmotic agent and at least one osmotic deposition vehicle,

wherein the method comprises at least one of the following:

controlling the amount of the at least one osmotic agent in the at least one osmotic subcoat, and

controlling the thickness of the at least one outer coat, thereby controlling the release rate of the at least one drug from the core of the microparticle into the external environment of use,

wherein the external environment of use is a dissolution medium,

wherein the temperature of the dissolution medium is 37°

C.+/−

0.5°

C.,

wherein the volume of the dissolution medium is selected from the group consisting of 500 ml and 900 ml,

wherein the dissolution medium is selected from the group consisting of water, a 0.1N HCl aqueous solution, a 0.1N HCl aqueous solution with sodium chloride added in an amount of 15.75 g/litre of the solution, a 0.1N HCl aqueous solution with added 0.1 wt % Cetrimide wherein the wt % is based on the weight of the solution, USP Buffer having a pH of 1.5, an acetate buffer having a pH of 4.5, a phosphate buffer having a pH of 6.5, a phosphate buffer having a pH of 6.8, a phosphate buffer having a of pH 7.4, and a 0.1N HCl aqueous solution with sodium chloride added in an amount of 14 g/litre of the solution,

wherein the dissolution medium is stirred by a USP type II paddle at 50 rotations per minute or 100 rotations per minute, and

wherein the pressure of the atmosphere on the dissolution medium is 1 atmosphere.

145. The method of claim 144, wherein the at least one outer coat comprises a plasticizer, and wherein the method further comprises:

controlling the amount of the plasticizer in the at least one outer coat.