Controlled release tablet

• US 5,945,125 A
• Filed: 06/21/1996
• Issued: 08/31/1999
• Est. Priority Date: 02/28/1995
• Status: Expired due to Term

• Current Assignee: Temple University
• Original Assignee: Temple University
• Inventors: Kim, Cherng-ju
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/667,238
• Time in Patent Office: 1,166 Days
• Field of Search: 424/473, 424/468
• US Class Current: 424/473
• 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 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence

Abstract

A controlled release tablet including a pharmaceutical agent and an excipient. The excipient includes at least about 60% of a water swellable polymer and a lubricant. The water swellable polymer is chosen such that the swelling rate of the polymer is equal to the dissolution rate of the swollen polymer. The excipient may also include such other ingredients as diluents, fillers, binders, solubilizers, emulsifiers, and other pharmacologically inactive compounds. The polymer is chosen with the pharmaceutical agent in mind such that the tablet will be fully dissolved at the same time that the last of the pharmaceutical agent is released.

Claims

1. A controlled release tablet consisting essentially of a single homogeneous mixture of a pharmaceutical agent selected from the group consisting of nifedipine, diclofenac sodium, salicylic acid, theophylline anhydrous, sulfapyridine, sulfadrazine, propranolol hydrochloride, diltiazem hydrochloride, glipizide, and sulfathiazole, a solubilizing agent, and an excipient, wherein said excipient comprises:

polyethylene oxide and a lubricant; and

wherein the pharmaceutical agent is released from the tablet at a rate expressed as M_t /M_T =ktⁿ where;

t is time,

M_t is the amount of the pharmaceutical agent which has been released at time t,

M_T is the total amount of the pharmaceutical agent contained in the tablet,

k is a constant, and

n is the release kinetics exponent; and

wherein the molecular weight and the solubility, respectively, of said polyethylene oxide and the pharmaceutical agent are selected such that n is about 0.89 to 1.0.

2. A controlled release tablet according to claim 1 wherein said polyethylene oxide has an average molecular weight in the range of about 900,000 to 5,000,000.

3. A controlled release tablet according to claim 1 wherein said lubricant is magnesium stearate.

4. A controlled release tablet according to claim 3 wherein said lubricant is present in an amount up to 3% by weight of said tablet.

5. A controlled release tablet according to claim 1 wherein said excipient further comprises a diluent.

6. A controlled release tablet according to claim 5 wherein said diluent is selected from the group consisting of lactose, dextrose, sucrose, and calcium phosphate.

7. A controlled release tablet according to claim 6 wherein said diluent is present in an amount of up to 50% by weight of said excipient.

8. A controlled release tablet according to claim 1 wherein said pharmaceutical agent is nifedipine.

9. A controlled release tablet according to claim 1 wherein said pharmaceutical agent is present in an amount of from about 10% to about 40% by weight of said tablet, including said excipient.

10. A controlled release tablet consisting essentially of a single homogenous mixture of a pharmaceutical agent and an excipient, wherein said excipient comprises:

19 to 43% by weight polyethylene oxide;

up to 3% by weight magnesium stearate; and

55to 80% by weight acacia; and

wherein said pharmaceutical agent is nifedipine and is present in an amount of from 9 to 13% by weight of said tablet.

11. A controlled release tablet consisting essentially of a single homogeneous mixture of a pharmaceutical agent nifedipine, a solubilizing agent, and an excipient, wherein said excipient comprises:

polyethylene oxide and

a lubricant; and

the swelling rate of said polyethylene oxide is equal to the dissolution rate of said polyethylene oxide when the polyethylene oxide is swollen.

12. The controlled release tablet of claim 11 wherein the excipient comprises at least 50% polyethylene oxide and a lubricant.

13. The controlled release tablet of claim 11 wherein said tablet has an aperture therethrough.

14. The controlled release tablet of claim 11 wherein the solubilizing agent is selected from the group consisting of polyethylene glycol, cyclodextrins, hydroxypropylcyclodextrins, lecithin, polyvinylpyrrolidone (PVP), acacia, lecithin gelatin, casein, and tragacanth.

15. The controlled release tablet of claim 11 wherein the polyethylene oxide has an average molecular weight in the range of about 900,000 to 5,000,000.

16. The controlled release tablet of claim 11 wherein said lubricant is magnesium stearate.

17. The controlled release tablet of claim 11 wherein said lubricant is present in an amount up to 3% by weight of said excipient.

18. The controlled release tablet of claim 11 wherein said excipient further comprises a diluent.

19. The controlled release tablet of claim 11 wherein said diluent is selected from the group consisting of lactose, dextrose, sucrose, and calcium phosphate.

20. The controlled release tablet of claim 11 wherein said diluent is present in an amount of up to 50% by weight of said excipient.

21. The controlled release tablet of claim 11 wherein said nifedipine is present in an amount of from about 10% to about 40% by weight of said tablet.

22. A controlled release pharmaceutical tablet consisting essentially of a single homogeneous mixture of the pharmaceutical agent nifidipine, a solubilizing agent selected from the group consisting of polyethylene glycol, acacia, lecithin gelatin, casein, and tragacanth, and an excipient, wherein said excipient comprises polyethylene oxide and a lubricant and at least 50 percent by weight of said excipient is polyethylene oxide having a molecular weight of from 900,000 to 5,000,000.

23. The controlled release tablet of claim 22 in which the solubilizing agent is selected from the group consisting of acacia, gelatin, casein and tragacanth.

24. The controlled release tablet of claim 22 in which the solubilizing agent is acacia.

25. The controlled release tablet of claim 22, 23, or 24 in which the tablet exhibits zero order release kinetics for the nifidipine when the tablet is swollen in the presence of aqueous media.