Novel drug compositions and dosage forms of topiramate

• US 20050175697A1
• Filed: 12/28/2004
• Published: 08/11/2005
• Est. Priority Date: 12/29/2003
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Seroff, Sylvia Lillian, Li, Shaoling, Jao, Frank, Shivanand, Padmaja, Edgren, David, Kimbel, Rhea, Yam, Noymi
• Application Number:
  US11/024,378
• Publication Number:
  US 20050175697A1
• Time in Patent Office: Days
• US Class Current: 424/470
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• 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
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• 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 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 29/02 without antiinflammatory effect
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 9/12 : Antihypertensives

Abstract

The present invention is directed to novel drug compositions and dosage forms comprising said drug compositions. The drug compositions of the present invention comprise a pharmaceutical agent and a solubilizing agent. The drug compositions of the present invention are particularly advantageous for use with low solubility and/or low dissolution rate pharmaceutical agents. The present invention is further directed to methods for manufacturing of said drug compositions and dosage forms. The present invention is further directed to methods of treatment comprising administration of said drug compositions and dosage forms.

Claims

1. A drug composition comprising topiramate and a solubilizing agent.

2. The drug composition of claim 1, wherein topiramate comprises greater than 11% by weight of the drug composition.

3. The drug composition of claim 2, wherein topiramate comprises between about 25% and about 55% by weight of the drug composition.

4. The drug composition of claim 1, wherein the solubilizing agent is a surfactant.

5. The drug composition of claim 4, wherein the surfactant comprises greater than about 10% by weight of the drug composition.

6. The drug composition of claim 4, wherein the surfactant is selected from polyoxyl 40 stearate, polyoxyl 50 stearate, KOLLIDON 12PF, KOLLIDON 17PF, KOLLIDON 25/30, KOLLIDON K90, LUTROL F68, LUTROL F87, LUTROL F127, LUTROL F108, MYRJ 52S, MYRJ 53, MYRJ 59FL, polyvinyl pyrrolidone K2932, sorbitan monopalmitate, sorbitan monostearate, glycerol monostearate, polyoxyethlene stearate, sucrose cocoate, polyoxyethylene 40 sorbitol lanolin derivative, polyoxyethylene 75 sorbitol lanolin derivative, polyoxyethylene 6 sorbitol beeswax derivative, polyoxyethylene 20 sorbitol beeswax derivative, polyoxyethylene 20 sorbitol lanolin derivative, polyoxyethylene 50 sorbitol lanolin derivative, polyoxyethylene 23 lauryl ether, polyoxyethylene 23 lauryl ether with butylated hydroxyanisole and citric acid added as preservatives, polyoxyethylene 2 cetyl ether with butylated hydroxyanisole and citric acid added as preservatives, polyoxyethylene 2 stearyl ether, polyoxyethylene 21 stearyl ether, polyoxyethylene 100 stearyl ether, polyoxyethylene 10 cetyl ether with butylated hydroxyanisole and citric acid added as preservatives, polyoxyethylene 20 cetyl ether with butylated hydroxyanisole and citric acid added as preservatives, polyoxyethylene 2 stearyl ether with butylated hydroxyanisole and citric acid added as preservatives, polyoxyethylene 10 stearyl ether with butylated hydroxyanisole and citric acid added as preservatives, polyoxyethylene 20 stearyl ether with butylated hydroxyanisole and citric acid added as preservatives, polyoxyethylene 21 stearyl ether with butylated hydroxyanisole and citric acid added as preservatives, polyoxyethylene 20 oleyl ether with butylated hydroxyanisole and citric acid added as preservatives, polyoxyethylene 40 stearate, polyoxyethylene 50 stearate, polyoxyethylene 100 stearate, sorbitan monopalmitate, sorbitan monostearate, sorbitan tristearate, polyoxyethylene 4 sorbitan monostearate, polyoxyethylene 20 sorbitan tristearate, or mixtures thereof.

7. The drug composition of claim 6, wherein the surfactant is selected from LUTROL F127, polyoxyl 40 stearate or polyoxyl 50 stearate.

8. The drug compsition of claim 7, wherein the surfactant is LUTROL F127.

9. The drug composition of claim 4, further comprising a structural polymer.

10. The drug composition of claim 9, wherein the structural polymer comprises between about 1% and about 90% by weight of the drug composition.

11. The drug composition of claim 10, wherein the structural polymer is selected from poly(ethylene oxide), poly(methylene oxide), poly(butylene oxide) and poly(hexylene oxide);

poly(carboxymethylcellulose), poly(alkali carboxymethylcellulose), poly(sodium carboxymethylcellulose), poly(potassium carboxymethylcellulose) poly(calcium carboxymethylcellulose), poly(lithium carboxymethylcellulose), hydroxypropylcellulose, hydroxypropylethylcellulose, hydroxypropylmethylcellulose, hydroxypropylbutylcellulose, hydroxypropylpentylcellulose, poly(vinylpyrrolidone), a bioerodible structural polymer, maltodextrin, a polyvinyl pyrrolidone, a polyvinylpyrrolidone vinyl acetate copolymer, lactose, glucose, raffinose, sucrose, mannitol, sorbitol, zylitol, or mixtures thereof.

12. The drug composition of claim 11, wherein the structural polymer is selected from MALTRIN M100, POLYOX N10 or POLYOX N80.

13. The drug composition of claim 12, wherein the structural polymer is POLYOX N80.

14. A dosage form comprising the drug composition of claim 4.

15. A dosage form comprising a core comprising the drug composition of claim 4 and a push layer comprising an osmopolymer;

a semi-permeable wall surrounding the core; and

an exit orifice through the semi-permeable wall for releasing the drug composition from the dosage form over a prolonged period of time.

16. The dosage form of claim 15, wherein the core further comprises a second drug composition comprising topiramate and a surfactant.

26. The drug composition of claim 4, wherein topiramate is micronized.

27. The drug composition of claim 4, wherein the surfactant is micronized.

28. A method of treating a disorder selected from the group consisting of epilepsy, migraine, glaucoma, ocular disorders, diabetic retinopathy, essential tremor, restless limb syndrome, obesity, weight loss, Type II Diabetes Mellitus, Syndrome X, impaired oral glucose tolerance, diabetic skin lesions, cluster headaches, neuralgia, neuropathic pain, diabetic neuropathy, elevated blood glucose levels, elevated blood pressure, elevated lipids, bipolar disorder, dementia, depression, psychosis, mania, anxiety, schizophrenia, OCD, PTSD, ADHD, impulse control disorders, ALS, asthma, autism, autoimmune disorders, chronic neurodegenerative disorders, acute neurodegeneration, sleep apnea and sleep disorders or promoting wound healing in a subject in need thereof comprising administering to the subject the drug composition of claim 4.

29. The method of claim 28, wherein the disorder is selected from the group consisting of epilepsy, migraine, diabetic retinopathy, diabetic neuropathy, diabetic skin lesions, obesity, weight loss, Type II Diabetes Mellitus, Syndrome X, impaired oral glucose tolerance, elevated blood glucose levels and elevated blood pressure.

32. The drug composition of claim 4, wherein the ratio of surfactant to topiramate is in the range of from about 1.3 to about 2.7.

33. The drug composition of claim 32, wherein the ratio of surfactant to topiramate is in the range of from about 1.5 to about 2.5.

34. The drug composition of claim 33, wherein the ratio of surfactant to topiramate is in the range of from about 1.8 to about 2.2.

35. The drug composition of claim 4, wherein the ratio of surfactant to topiramate is in the range of from about 0.1:

1 to about 3;

1.

36. The drug composition of claim 35, wherein the ratio of surfactant to topiramate is in the range of from about 0.25:

1 to about 2.5;

1.

37. The drug composition of claim 36, wherein the ratio of surfactant to topiramate is in the range of from about 0.5:

1 to about 2;

1.

38. The drug composition of claim 37, wherein the ratio of surfactant to topiramate is in the range of from about 1:

1 to about 2;

1.

39. The drug composition of claim 38, wherein the ratio of surfactant to topiramate is in the range of from about 1.5:

1 to about 2;

1.

17. A dosage form comprising

(a) a-core comprising a first drug composition, a second drug composition and a push layer comprising an osmopolymer, wherein each of the first and second drug compositions comprise topiramate and an independently selected solubilizing agent;

(b) a semi-permeable wall surrounding the core; and

(c) an exit orifice through the semi-permeable wall for releasing the drug compositions from the dosage form over a prolonged, period of time.

18. The dosage form of claim 17, wherein the concentration of topiramate in the first drug composition is less than the concentration of topiramate in the second drug composition.

19. The dosage form of claim 17, which provides a substantially ascending rate of release.

20. The dosage form of claim 17, which provides a substantially ascending drug plasma concentration.

30. A method of treating a disorder selected from the group consisting of epilepsy, migraine, glaucoma, ocular disorders, diabetic retinopathy, essential tremor, restless limb syndrome, obesity, weight loss, Type II Diabetes Mellitus, Syndrome X, impaired oral glucose tolerance, diabetic skin lesions, cluster headaches, neuralgia, neuropathic pain, diabetic neuropathy, elevated blood glucose levels, elevated blood pressure, elevated lipids, bipolar disorder, dementia, depression, psychosis, mania, anxiety, schizophrenia, OCD, PTSD, ADHD, impulse control disorders, ALS, asthma, autism, autoimmune disorders, chronic neurodegenerative disorders, acute neurodegeneration, sleep apnea and sleep disorders or promoting wound healing in a subject in need thereof comprising administering to the subject the dosage form of claim 17.

31. A method of claim 30, wherein the disorder is selected from the group consisting of epilepsy, migraine, diabetic retinopathy, diabetic neuropathy, diabetic skin lesions, obesity, weight loss, Type II Diabetes Mellitus, Syndrome X, impaired oral glucose tolerance, elevated blood glucose levels and elevated blood pressure.

21. A dosage form comprising:

(a) a core comprising a first drug composition, a second drug composition and a push layer comprising an osmopolymer;

(b) a semi-permeable wall surrounding the core; and

(c) an exit orifice through the semi-permeable wall for releasing the first drug composition and the second drug composition from the dosage form over a prolonged period of time;

wherein the first drug composition comprises between about 25% and about 40% by weight of topiramate and between about 25% and about 50% by weight of a surfactant; and

the second drug composition comprises between about 30% and about 50% by weight of topiramate and between about 45% and about 60% by weight of a surfactant.

22. The dosage form of claim 21, wherein the first drug composition further comprises between about 10% and about 35% by weight of a structural polymer, and the second drug composition further comprises between about 0% and about 10% by weight of a structural polymer.

23. The dosage form of claim 22, wherein the surfactant in both the first and second drug compositions is LUTROL F127 and the structural polymer in both the first and second drug compositions is POLYOX N80.

24. A dosage form comprising:

(a) a core comprising a first drug composition, a second drug composition and a push layer comprising an osmopolymer;

(b) a semi-permeable wall surrounding the core; and

(c) an exit orifice through the semi-permeable wall for releasing the first drug composition and the second drug composition from the dosage form over a prolonged period of time;

wherein the first drug composition comprises between about 5% and about 25% by weight of topiramate and between about 1% and 35% by weight of a surfactant, and the second drug composition comprises between about 10% and about 25% by weight of topiramate and between about 10% and about 35% by weight of a surfactant.

25. The dosage form of claim 24, wherein the first drug composition further comprises between about 75% and about 95% by weight of a structural polymer, and the second drug composition further comprises between about 65% and about 80% by weight of a structural polymer.