Osmotic drug delivery system

• US 6,814,979 B2
• Filed: 12/20/2002
• Issued: 11/09/2004
• 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., Flanner, Henry H., Pinkett, Jill E., Rudnic, Edward M., Wassink, Sandra E., Burnside, Beth A.
• Primary Examiner(s): Hartley, Michael G.
• Assistant Examiner(s): LANDAU, SHARMILA GOLLAMUDI
• Application Number:
  US10/324,187
• Publication Number:
  US 20030143273A1
• Time in Patent Office: 690 Days
• Field of Search: 424/400, 424/464, 424/465, 424/468, 424/472, 424/473, 424/474, 424/480, 424/482, 424/484, 424/488, 514/866, 514/960, 514/964
• 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. 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, said composition comprising;

(i) a pharmaceutical agent that has limited solubilty in water or in aqueous environments at physiological pH;

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

(iii) at least one non-swelling osmotic agent, and (iv) at least one lubricant, said composition within said wall excluding a polymer that swells.

2. The system of claim 1, wherein said at least one non-swelling solubilizing agent is selected from (A) agents that inhibit crystal formation of said pharmaceutical agent or acts by complexation therwith;

(B) high HLB (hydrophilic-lipophilic balance) surfactants;

(C) citrate esters; and

(D) stearate salts; and

combinations thereof.

3. The system of claim 2, wherein said at least one non-swelling solubilizing agent is at least one agent that inhibits crystal formation of said pharmaceutical agent.

4. The system of claim 3, wherein said at least one agent that inhibits crystal formation of said pharmaceutical agent is selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, cyclodextrins, gelatin, maltodextrin, sorbitol, and polyglycenyl mixed vegetable fatty acid esters.

5. The system of claim 2, wherein said at least one non-swelling solubilizing agent is at least one high HLB (hydrophilic-lipophilic balance) surfactant.

6. The system of claim 5, wherein said at least one high HLB (hydrophilic-lipophilic balance) surfactant is selected from the group consisting of sodium lauryl sulfate, polysorbates, polyglycolized glycerides, and derivatives thereof.

7. The system of claim 2, wherein said at least one non-swelling solubilizing agent is at least one stearate salt.

8. The system of claim 7, wherein said at least one stearate salt is selected from the group consisting of magnesium stearate, sodium stearate, calcium stearate, and zinc stearate.

9. The composition of claim 1, wherein said at least one osmotic agent is selected from the group consisting of xylitol, mannitol, sorbitol, inositol, sucrose, lactose, dextrose, and maltodextrins.

10. The composition of claim 1, wherein said as least one lubricant is selected from the group consisting of magnesium stearate, calcium stearate, zinc stearate, stearic acid, polyethylene glycol, glyceryl behenate, sodium lauryl sulfate, sodium stearyl fumarate, and hydrogenated vegetable oil.

11. The system of claim 1, wherein said pharmaceutical agent is selected from cough suppressants, antihistamines, decongestants, antihypertensives, calcium channel blockers, antidiabetic agents, proton pump inhibitors, H2 receptor antagonists, carbamazepine, anti-Parkinsonian agents, and antiviral agents.

12. The system of claim 1, wherein said pharmaceutical agent is selected from dextromethorphan hydrobromide, codeine, chlorpheniramine maleate, brompheniramine maleate, loratidine, astemizole, diclofenac sodium, terfenadine, pseudoephedrine, phenylephrine, nifedipine, verapamil, enalapril, metoprolol, metoprolol succinate, metoprolol fumarate, metoprolol tartarate, verapamil, diltiazam, nimodipine, felodipine, nicardipine, isradipine amlodipine, glipizide, ibromectin, omeprazole, cimetidine, ranitidine, famotidine, nizatidine, carbamazepine, selegiline, carbidopa/levodopa, pergolide, bromocriptine, amantadine, trihexyphenidyl, acyclovir, famciclovir, foscarnet, ganciclovir, didanosine, stavudine, zalcitabine, zidovudine, amantadine, interferon alpha, ribavirin, rimantadine, propiomazine, phenytoin, tacrine, propiazam, proplazam, and salts thereof.

13. The system of claim 1, wherein the pharmaceutical agent is selected from glipizide, omeprazole and nefidipine.

14. The systen of claim 1, wherein the pharmaceutical agent is glipizide.

15. The system of claim 1, wherein the semipermeable wall comprises cellulose acetate and triethyl citrate.