Uniform delivery of topiramate over prolonged period of time with enhanced dispersion formulation

• US 20050058707A1
• Filed: 08/03/2004
• Published: 03/17/2005
• Est. Priority Date: 08/06/2003
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Li, Shaoling, Yam, Noymi V., Reyes, Iran, Wong, Patrick S.L., Shivanand, Padmaja
• Application Number:
  US10/910,040
• Publication Number:
  US 20050058707A1
• Time in Patent Office: Days
• US Class Current: 424/468
• 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 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants

Abstract

Compositions and dosage forms for enhanced dispersion of topiramate in a controlled release dosage form delivered as a dry or substantially dry erodible solid at a uniform rate over a prolonged period of time are described.

Claims

1. A controlled release dosage form comprising a compound, characterized by having a high dosage, low solubility and poor dissolution rate or a pharmaceutically acceptable acid addition salt thereof, a disintegrant and no surfactant adapted to release as an erodible solid over a prolonged period of time at a uniform rate.

2. The dosage form of claim 1 wherein the compound is topiramate.

3. The dosage form of claim 1 wherein the prolonged period of time is six hours or greater.

4. The dosage form of claim 1 wherein the prolonged period of time is eight hours or greater.

5. The dosage form of claim 1 wherein the prolonged period of time is 10 hours or greater.

6. The dosage form of claim 1 wherein the compound is released at a rate of at least 2 mg/hr.

7. The dosage form of claim 6 wherein the prolonged period of time is six hours or greater.

8. A bioerodible composition comprising a compound characterized by having a high dosage, low solubility and poor dissolution rate or a pharmaceutically acceptable acid addition salt thereof adapted to release the compound over a prolonged period of time at a uniform rate of release of at least 2 mg/hr with no surfactant.

9. The composition of claim 8 wherein the compound is topiramate.

10. The composition of claim 9 further comprising polyethylene oxide and polyvinylpyrrolidone.

11. The composition of claim 10 wherein the prolonged period of time is six hours or greater.

12. The composition of claim 8 wherein the uniform rate of release is not more than 60 mg/hr.

13. The composition of claim 8 further comprising a hydrophilic polymer carrier.

14. The composition of claim 8 further comprising a disintegrant.

15. The composition of claim 13 further comprising a disintegrant

16. A method of treating a condition in a subject responsive to administration of a compound characterized by having a high dosage, low solubility and poor dissolution rate or a pharmaceutically acceptable acid addition salt thereof which comprises orally administering to the subject a dosage form adapted to release the compound at a uniform rate of release over a prolonged period of time with no surfactant.

17. The method of claim 16 wherein the compound is topiramate.

18. The method of claim 17 wherein the dosage form contains between 50 and 1200 mg of the compound.

19. The method of claim 18 wherein the dosage form comprises an osmotic material.

20. A dosage form comprising:

a) a wall defining a compartment, at least a portion of the wall being semipermeable;

b) an exit orifice formed or formable in the wall; and

c) an expandable layer located within the compartment remote from the exit orifice and in fluid communication with the semipermeable portion of the wall; and

d) a drug layer located within the compartment adjacent the exit orifice, the drug layer comprising a compound characterized by having a high dosage, low solubility and poor dissolution rate or a pharmaceutically acceptable acid addition salt thereof with no surfactant.

21. The dosage form of claim 20 wherein the compound is topiramate.

22. The dosage form of claim 20 further comprising a flow-promoting layer between the wall and the drug layer.

23. A method of treating a condition responsive to administration of a compound comprising administering to a subject a compound characterized by having a high dosage, low solubility and poor dissolution rate or a pharmaceutically acceptable acid addition salt thereof with no surfactant which comprises maintaining over a prolonged period of time a steady state concentration of compound in the plasma of a subject between 5 ng/ml and 2500 ng/ml, wherein the quotient formed from [C_max−

C_min]/C_avg is 3 or less.

24. The method of claim 23 wherein the compound is topiramate.

25. The method of claim 23 wherein the quotient is 2 or less.

26. The method of claim 23 wherein the quotient is 1 or less.