Controlled release of drugs delivered by sublingual or buccal administration

• US 5,888,534 A
• Filed: 04/29/1997
• Issued: 03/30/1999
• Est. Priority Date: 06/13/1995
• Status: Expired due to Term

• Current Assignee: Pentech Pharmaceuticals Incorporated
• Original Assignee: Pentech Pharmaceuticals Incorporated
• Inventors: Hassan, Emad Eldin, El-Rashidy, Ragab, Ronsen, Bruce
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Spear, James M.
• Application Number:
  US08/841,250
• Time in Patent Office: 700 Days
• Field of Search: 424/435, 424/473, 424/464, 424/468, 424/465
• US Class Current: 424/435
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/277 having a ring, e.g. verapamil
• CPC Class Codes: A61K 31/473 ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs

Abstract

A composition providing a relatively slow release of water-soluble drugs, such as apomorphine, for delivery via the sublingual or buccal routes.

Claims

1. A composition providing a relatively slow release of water-soluble drugs by sublingual route and consisting essentially of:

a water-soluble drug which is a member of the group consisting of apomorphine hydrochloride, albuterol sulfate, timolol maleate, verapamil hydrochloride and naloxone hydrochloride;

an osmotic agent;

a swellable hydrophilic carrier;

and a water dispersible polymer;

the composition having a T₉₀ value in the range of more than about 25 to about 300; and

the composition having the ratio of the amount by weight of the osmotic agent to the amount by weight of the swellable hydrophilic carrier in the range of about 0.3 to about 4.

2. The composition of claim 1 containing from about 2 milligrams to about 40 milligrams of the water-soluble drug.

3. The composition of claim 1 wherein the ratio of the amount by weight of the osmotic agent to the amount by weight of the swellable hydrophilic carrier is less than about 4.

4. The composition of claim 1 containing from about 10 milligrams to about 40 milligrams of the water-soluble drug.

5. The composition of claim 1 wherein the osmotic agent is selected from the group consisting of sugars, glycerin, polyelectrolytes, organic salts and inorganic salts.

6. The composition of claim 1 wherein the osmotic agent is mannitol.

7. The composition of claim 1 wherein the swellable hydrophilic carrier is selected from the group consisting of ethyl cellulose, microcrystalline cellulose, cross-linked polyvinyl pyrrolidone, dicalcium phosphate, calcium carbonate and silica.

8. The composition of claim 1 wherein the swellable hydrophilic carrier is microcrystalline cellulose.

9. The composition of claim 1 wherein the water dispersible polymer is selected from the group consisting of methylcellulose, carboxymethyl cellulose, hydroxymethylcellulose, hydroxypropyl methylcellulose, alginates, gelatin, guar gum, gum tragacanth, gum acacia, polyacrylic acid, polymethacrylic acid, polysilicic acid, polylactic acid, polymaleic acid, polyvinyl alcohol, polyethylene glycol, polyvinyl pyrrolidone, nonionic blocked polymers, carbomers, polycarbophils, and water soluble starches.

10. The composition of claim 1 wherein the water dispersible polymer is methylcellulose.

11. The composition of claim 1 wherein the water dispersible polymer is carboxymethylcellulose.

12. The composition of claim 1 wherein the water dispersible polymer is hydroxypropyl methylcellulose.

13. The composition of claim 1 wherein the water dispersible polymer is sodium alginate.

14. The composition of claim 1 wherein the water dispersible polymer is gum tragacanth.

15. The composition of claim 1 wherein the water dispersible polymer is polyvinyl pyrrolidone.

16. The composition of claim 1 wherein the water dispersible polymer is a carbomer.

17. The composition of claim 1 wherein the water dispersible polymer is polyethylene glycol.

18. The composition of claim 1 wherein the ater dispersible polymer is gelatin.

19. The composition of claim 1 wherein the water dispersible polymer is ascorbic acid palmitate.

20. The composition of claim 1 wherein the water dispersible polymer constitutes from about 0.5 weight percent to about 20 weight percent based on the weight of the composition.

21. The composition of claim 1 wherein the swellable hydrophilic carrier constitutes from about 25 weight percent to about 40 weight percent based on the weight of the composition.

22. The composition of claim 1 wherein the ratio of the amount by weight of the osmotic agent to the amount by weight of the swellable hydrophilic carrier is less than about 2.