Soluble form osmotic dose delivery system

• US 6,514,532 B2
• Filed: 12/28/2001
• Issued: 02/04/2003
• 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): Dees, Jose′ G.
• Assistant Examiner(s): LANDAU, SHARMILA GOLLAMUDI
• Application Number:
  US10/035,077
• Publication Number:
  US 20020102306A1
• Time in Patent Office: 403 Days
• Field of Search: 424/400, 424/464, 424/465, 424/472, 424/473, 424/474, 424/476, 424/479, 424/480, 424/482, 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 semi-permeable 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. A method of preparing an osmotic pharmaceutical delivery system, comprising:

(a) adding water to a composition comprising (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 said pharmaceutical agent; and

(iii) at least one non-swelling osmotic agent, wherein said composition is 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, to provide said composition as a wet granulation mass;

(b) drying said wet granulation mass to provide dry granules including components (i), (ii), and (iii) hereinabove;

(c) compressing said granules into at least one tablet; and

(d) coating each of said at least one tablet(s) with a semipermeable wall that maintains its integrity during pharmaceutical delivery; and

(e) providing at least one passage through said semipermeable wall.

2. The method 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 method 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 method of claim 1 wherein said semipermeable wall comprises cellulose acetate and triethyl citrate.

5. The method 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 method of claim 1 wherein the pharmaceutical agent has limited aqueous solubility at physiological pH.

7. The method of claim 6 wherein the pharmaceutical agent is nifedipine.

8. The method of claim 1 wherein the composition within said wall further comprises a lubricant.

9. The method of claim 1 wherein the at least one non-swelling osmotic agent is a sugar.

10. The method of claim 9 wherein the sugar has no more than ten rings.

11. The method of claim 10 wherein the sugar has no more than five rings.

12. The method of claim 11 wherein the sugar is selected from the group consisting of monosaccharides, disaccharides, and trisaccharides.

13. The method of claim 11 wherein the sugar is selected from the group consisting of fructose, lactose, xylitol, inositol, and sorbitol.

14. The method of claim 1 wherein said pharmaceutical agent is glipizide.

15. The method of claim 14 wherein (i) the pharmaceutical agent is glipizide;

(ii) the at least one non-swelling solubilizing agent is sodium lauryl sulfate; and

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