Soluble form osmotic dose delivery system

• US 6,284,276 B1
• Filed: 07/11/2000
• Issued: 09/04/2001
• Est. Priority Date: 10/25/1996
• Status: Expired due to Term

• Current Assignee: Supernus Pharmaceuticals Incorporated
• Original Assignee: Shire Laboratories, Inc. (Supernus Pharmaceuticals Incorporated)
• Inventors: Couch, Richard A., Rudnic, Edward M., Wassink, Sandra E., Burnside, Beth A., Flanner, Henry H., Pinkett, Jill E.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Seidleck, Brian K.
• Application Number:
  US09/613,202
• Time in Patent Office: 420 Days
• Field of Search: 424/473, 424/476, 424/479, 424/480, 424/482, 514/356, 514/960
• US Class Current: 424/473
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas

Abstract

Disclosed is an osmotic pharmaceutical delivery system comprising (a) a semipermeable wall that maintains its integrity during pharmaceutical delivery and which has at least one passage therethrough; (b) a single, homogeneous composition within said wall, which composition consists essentially of (i) a pharmaceutically active agent, (ii) at least one non-swelling solubilizing agent which enhances the solubility of the pharmaceutically active agent; (iii) at least one non-swelling osmotic agent and (iv) a non-swelling wicking agent dispersed throughout the composition which enhances the surface area contact of the pharmaceutical agent with the incoming aqueous fluid.

Claims

1. An osmotic pharmaceutical delivery system comprising (a) a semipermeable wall that maintains its integrity during pharmaceutical delivery and which has at least one passage therethrough;

and (b) a composition within said wall, which composition comprises (i) a pharmaceutical agent that has a limited solubility in water or physiological environments;

(ii) at least one non-swelling solubilizing agent which enhances the solubility of the pharmaceutical agent; and

(iii) at least one non-swelling osmotic agent, said composition being free of an agent that provides a physical force other than by osmotic pressure for delivering the pharmaceutical agent whereby the pharmaceutical agent is delivered through the passageway by osmosis rather than by another force.

2. The pharmaceutical delivery system of claim 1 wherein said at least one non-swelling solubilizing agent is selected from the group consisting of (i) agents that inhibit crystal formation of the pharmaceutical;

(ii) a surfactant;

(iii) citrate esters; and

(iv) combinations thereof.

3. The pharmaceutical delivery system of claim 2 wherein said non-swelling solubilizing agent comprises the combination of at least one agent that inhibits crystal formation of the pharmaceutical with at least one surfactant.

4. The pharmaceutical delivery system of claim 1 wherein said semipermeable wall comprises cellulose acetate and triethyl citrate.

5. The pharmaceutical delivery system of claim 1 wherein said at least one solubilizing agent is selected from the group consisting of sodium lauryl sulfate and a low molecular weight polyvinylpyrrolidone, and combinations thereof.

6. The pharmaceutical delivery system of claim 5 wherein said at least one solubilizing agent is a combination of sodium lauryl sulfate and a low molecular weight polyvinylpyrrolidone.

7. The pharmaceutical delivery system of claim 1 wherein the osmotic agent is selected from the group consisting of xylitol and mannitol.

8. The pharmaceutical delivery system of claim 1 wherein the pharmaceutical agent has limited aqueous solubility at physiological pH.

9. The pharmaceutical delivery system of claim 8 wherein the pharmaceutical agent is nifedipine.

10. The pharmaceutical delivery system of claim 1 wherein the composition within said wall further comprises a lubricant.

11. The pharmaceutical delivery system of claim 1 wherein (i) the pharmaceutical agent is nifedipine;

(ii) the at least one non-swelling solubilizing agent is polyvinylpyrrolidone; and

(iii) the at least one non-swelling osmotic agent comprises at least one sugar.

12. The pharmaceutical delivery system of claim 11 wherein the at least one non-swelling solubilizing agent is a low molecular weight polyvinylpyrrolidone.

13. The pharmaceutical delivery system of claim 11 which further comprises a high hydrophilic-lipophilic balance micelle-forming surfactant as a non-swelling solubilizing agent.

14. The pharmaceutical delivery system of claim 13 wherein the surfactant is sodium lauryl sulfate.

15. The pharmaceutical delivery system of claim 11 wherein the at least one sugar is xylitol.

16. The pharmaceutical delivery system of claim 1 wherein the pharmaceutical agent is released through said at least one passage.

17. The pharmaceutical delivery system of claim 1 wherein the wall has a plurality of passages therethrough.

18. The pharmaceutical delivery system of claim 1 wherein the non-swelling solubilizing agent is selected from the group consisting of (i) agents that inhibit crystal formation of the pharmaceutical or otherwise act by complexation therewith;

(ii) a high HLB (hydrophilic-lipophilic balance) micelle-forming surfactant;

(iii) citrate esters; and

combinations thereof.

19. The pharmaceutical delivery system of claim 18 which comprises the combination of at least one complexation agent with at least one anionic surfactant.

20. The pharmaceutical delivery system of claim 19 wherein the combination is selected from the group consisting of (i) a polyvinylpyrrolidone and sodium lauryl sulfate and (ii) a non-swellable polyethyleneglycol and sodium lauryl sulfate.

21. The pharmaceutical delivery system of claim 1 wherein the at least one non-swelling osmotic agent is a sugar.

22. The pharmaceutical delivery system of claim 21 wherein the sugar has no more than ten rings.

23. The pharmaceutical delivery system of claim 22 wherein the sugar has no more than five rings.

24. The pharmaceutical delivery system of claim 23 wherein the sugar is selected from the group consisting of monosaccharides, disaccharides, and trisaccharides.

25. The pharmaceutical delivery system of claim 23 wherein the sugar is selected from the group consisting of fructose, lactose, xylitol, inositol, and soribitol.

26. The pharmaceutical delivery system of claim 25 wherein the sugar is coated with a hydrophobic material.