Controlled release formulation

• US 4,792,452 A
• Filed: 07/28/1987
• Issued: 12/20/1988
• Est. Priority Date: 07/28/1987
• Status: Expired due to Term

• Current Assignee: ER Squibb & Sons LLC (Bristol-Myers Squibb Company)
• Original Assignee: E R Squibb & Sons Incorporated
• Inventors: Howard, John R., Timmins, Peter
• Primary Examiner(s): Dixon, Jr., William R.
• Assistant Examiner(s): Green, Anthony J.
• Application Number:
  US07/078,505
• Time in Patent Office: 511 Days
• Field of Search: 424/468, 424/475, 424/479, 424/480, 424/482, 536/3, 514/54
• US Class Current: 424/475
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Abstract

A controlled release pharmaceutical formulation is provided which releases a pharmaceutical of a basic character at a controlled rate regardless of the pH of the environment, which formulation includes a basic pharmaceutical, up to about 45% by weight of a pH dependent polymer which is a salt of alginic acid, such as sodium alginate, up to about 35% by weight of a pH-independent hydrocarbon gelling agent having a viscosity of up to about 100,000 centipoises in 2% solution at 20° C., binder and excipients.

Claims

1. A controlled release pharmaceutical formulation from which a pharmaceutical of a basic character is released at a controlled rate irrespective of the pH of the environment, consisting essentially of a pharmaceutical of a basic character, a pH-dependent polymer which is a salt of alginic acid, in an amount of from about 15 to about 45% by weight of the formulation, said salt of alginic acid having a viscosity of within the range of from about 4 to about 500 centipoises in 1% solution at 25°

C.;

a pH-independent hydrocolloid gelling agent having a viscosity within the range of from about 50 to about 100,000 centipoises in 2% solution at 20°

C., in an amount within the range of from about 3 to about 35% by weight of the formulation, and binder, said formulation being free of calcium ion.

2. The formulation as defined in claim 1 wherein the pH-dependent salt of alginic acid is employed in a weight ratio to the pH-independent hydrocolloid gelling agent of within the range of from about 0.1:

1 to about 10;

1.

3. The formulation as define in claim 1 wherein said pH-dependent salt of alginic acid is employed in an amount within the range of from about 20 to about 35% by weight of the formulation and the pH-independent hydrocolloid gelling agent is employed in an amount within the range of from about 3 to about 20% by weight of said formulation.

4. The formulation as defined in claim 1 wherein said pharmaceutical of a basic character is employed in an amount of from about 20 to about 75% by weight of said formulation.

5. The formulation as defined in claim 1 in the form of a tablet.

6. The formulation as defined in claim 1 wherein said pharmaceutical of a basic character is a calcium antagonist.

7. The formulation as defined in claim 6 wherein said calcium antagonist is a salt of verapamil, a salt of diltiazem, a salt of nicardipine, a salt of nifedipine, a salt of gallapomil or a salt of cinnarizine.

8. The formulation as defined in claim 1 wherein said pharmaceutical of a basic character is a beta blocker, antihistamine, sympathomimetic, beta adrenergic agonist or bronchodilator, or central nervous system drug.

9. The formulation as defined in claim 8 wherein said beta blocker is a salt of propranolol, a salt of metoprolol, or a salt of nadolol, said antihistamine is a salt of chlorpheniramine, a salt of diphenhydramine, said sympathomimetic is a salt of phenylpropanolamine or a salt of pseudoephedrine, said beta adrenergic agonist is a salt of salbutamol, or a salt of terbutaline, and said central nervous system drug is a salt of thioridazine, a salt of trifluoperazine, or chlorpromazine.

10. The formulation as defined in claim 1 wherein said hydrocolloid gelling agent is hydroxypropylmethyl cellulose, methyl cellulose, hydroxypropyl cellulose, or a mixture of two or more of such hydrocolloid gelling agents.

11. The formulation as defined in claim 1 wherein said binder is hydroxypropylmethyl cellulose having a viscosity of from about 5 to about 15 centipoises, hydrolyzed gelatin or polyvinyl pyrrolidone.

12. The formulation as defined in claim 1 further including one or more excipients.

13. The formulation as defined in claim 12 wherein said excipient is microcrystalline cellulose, lactose, sugar, mannitol, sorbitol, inorganic salts or cellulose.

14. The formulation as defined in claim 1 further including a lubricant.

15. The formulation as defined in claim 14 wherein said lubricant is magnesium stearate or stearic acid.

16. The formulation as defined in claim 1 wherein said salt of alginic acid is sodium alginate or potassium alginate.

17. The formulation as defined in claim 1 wherein the salt of alginic acid has a viscosity of within the range of from about 4 to about 350 centipoises in 1% solution at 25°

C.

18. The formulation as defined in claim 1 containing alginic acid salts of two different viscosities.

19. The formulation as defined in claim 1 further including a coating layer.

20. The formulation as defined in claim 1 wherein said pharmaceutical of a basic character is verapamil hydrochloride, said salt of alginic acid is sodium alginate, said hydrocolloid gelling agent is hydroxypropylmethyl cellulose having a viscosity of from about 50 to about 100,000 centipoises, said binder is hydroxypropylmethyl cellulose having a viscosity of from about 5 to about 15 centipoises, further including microcrystalline cellulose and lactose as binders-excipients and further including magnesium stearate as a lubricant.