Sustained release preparations

• US 20050265955A1
• Filed: 05/28/2004
• Published: 12/01/2005
• Est. Priority Date: 05/28/2004
• Status: Abandoned Application

• Current Assignee: Mallinckrodt Incorporated (Mallinckrodt plc)
• Original Assignee: Mallinckrodt Incorporated (Mallinckrodt plc)
• Inventors: Lang, John F., Cunningham, John P., Raman, Siva N.
• Application Number:
  US10/857,533
• Publication Number:
  US 20050265955A1
• Time in Patent Office: Days
• US Class Current: 424/78.120
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• CPC Class Codes: A61K 47/585 Ion exchange resins, e.g. polystyrene sulfonic acid resin
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/5036 Polysaccharides, e.g. gums, alginate; Cyclodextrin

Abstract

Disclosed are sustained release drug particles suitable for forming sustained release oral pharmaceutical compositions. The sustained release drug particles comprise a drug-ion exchange resin complex and a water-permeable, diffusion barrier surrounding at least a portion of the drug-ion exchange resin complex. The diffusion barrier comprises a film-forming polymer and is free or contains no substantial traces of organic solvent. Also disclosed are oral pharmaceutical compositions, for example, oral suspensions, comprising the sustained release drug particles, a method for the controlled administration of a drug to a patient, and a method for manufacturing the sustained release drug particles. The method of manufacturing involves the use of an aqueous coating composition comprising a water-permeable film-forming polymer such as ethylcellulose.

Claims

1. An oral pharmaceutical composition comprising ion exchange resin particles having particle sizes from about 30 microns to about 500 microns;

at least one pharmaceutically active drug releasably bound to the particles to form a drug-ion exchange resin complex, wherein the drug-ion exchange resin complex is coated with an aqueous based diffusion barrier which comprises from about 1% to about 60%, by weight of the resin particles, of a water-permeable film-forming polymer which contains no substantial traces of an organic solvent.

2. The composition of claim 1, wherein the particle size of the ion exchange resin particles is from about 40 microns to about 200 microns.

3. The composition of to claim 1, wherein the ion exchange resin particles are regularly shaped, irregularly shaped, or both.

4. The composition of claim 1, wherein the ion exchange resin has an ion-exchange capacity of less than 6.0 meq/gram.

5. The composition of claim 1, wherein the drug comprises from about 1% to about 50% by weight of the drug-ion exchange resin complex.

6. The composition of claim 1, wherein the water-permeable film-forming polymer comprises ethylcellulose.

7. The composition of claim 1, which provides a controlled release of active drug in vivo.

8. The composition of claim 1, wherein the drug-ion exchange resin complex contains a solvating agent.

9. The composition of claim 8, wherein the solvating agent comprises polyethylene glycol.

10. The composition of claim 1, wherein the pharmaceutically active drug is selected from the group consisting of antitussive expectorants, bronchodilators, antihistamines, digestive tract antispasmodics, antipsychotic drugs, antianxiety drugs, antidepressants, antipyretic analgesics, opioid analgesic drugs, coronary dilators, hypotensive drugs, peripheral vasodilators/vasoconstrictors, antibiotics, chemo-therapeutic drugs, antituberculosis drugs, and antiprotozoan drugs.

11. The composition of claim 1, wherein the pharmaceutically active drug is selected from the group consisting of dehydrocholic acid, diflunisal, ethacrynic acid, fenoprofen, furosemide, gemfibrozil, ibuprofen, naproxen, phenyloin, probenecid, sulindac, theophylline, salicylic acid, acetylsalicylic acid, acetophenazine, amitriptyline, amphetamine, benztropine, biperiden, bromodiphenhydramine, brompheniramine, carbinoxamine, chlorcyclizine, chlorpheniramine, chlorphenoxamine, chlorpromazine, clemastine, clomiphene, clonidine, codeine, cyclizine, cyclobenzaprine, cyproheptadine, desipramine, dexbrompheniramine, dexchlorpheniramine, dextroamphetamine, dextromethorphan, diazepam, dicyclomine, diphemanil, diphenhydramine, doxepin, doxylamine, ergotamine, fexofenadine, fluphenazine, haloperidol, hydrocodone, hydroxychloroquine, hydroxyzine, hyoscyamine, imipramine, levopropoxyphene, maprotiline, meclizine, mepenzolate, meperidine, mephentermine, mesoridazine, methadone, methdilazine, methscopolamine, methysergide, metoprolol, nortriptylene, noscapine, nylindrin, orphenadrine, papaverine, pentazocine, phendimetrazine, phentermine, phenylpropanolamine, pyrilamine, tripelennamine, triprolidine, promazine, propoxyphene, propanolol, pseudoephedrine, pyrilamine, quinidine, scopolamine, dextromethorphan, chlorpheniramine, aminocaproic acid, aminosalicylic acid, hydromorphone, isoxsuprine, levorphanol, melphalan, morphine, nalidixic acid, oxycodone, tramadol, and paraminosalicylic acid, and any combination thereof, and pharmaceutically acceptable salts thereof.

12. The composition of claim 1, which is a liquid.

13. A method for manufacturing sustained release drug particles for use in the manufacture of a sustained release preparation comprising contacting particles of an ion exchange resin with a pharmaceutically active drug to form a drug-ion exchange resin complex wherein the particle size of the ion exchange resin particles is from about 30 microns to about 500 microns;

and coating the drug-ion exchange resin complex with an aqueous suspension of a water-permeable film-forming polymer which contains no substantial traces of an organic solvent such that the resulting coating has an average thickness of at least about 10 microns.

14. The method of claim 13, wherein the particle size of the ion exchange resin particles is from about 40 microns to about 200 microns.

15. The method of claim 13, wherein the drug comprises from about 1% to about 50% by weight of the drug-ion exchange resin complex.

16. The method of claim 13, wherein the water-permeable film-forming polymer comprises ethylcellulose.

17. The method of claim 13, comprising impregnating a solvating agent on to the drug-ion exchange resin complex.

18. The method of claim 17, wherein the solvating agent is polyethylene glycol.

19. A pharmaceutical composition comprising:

ion exchange resin particles having particle sizes from about 30 microns to about 500 microns;

at least one pharmaceutically active drug releasably bound to the ion exchange resin particles to form a drug-ion exchange resin complex; and

a pharmaceutically acceptable carrier, wherein the drug-ion exchange resin complex is coated with an aqueous based diffusion barrier which comprises a water-permeable film-forming polymer in an amount of from about 1% to about 60%, by weight of the ion exchange resin particles.

20. The composition of claim 19, wherein the pharmaceutically acceptable carrier is a liquid.

21. The pharmaceutical composition of claim 19, wherein the composition is a liquid.

22. A method for the controlled administration of a drug to a patient comprising administering to the patient a therapeutically acceptable dose of a composition comprising a diffusion barrier coated drug-ion exchange resin complex wherein the diffusion barrier is present in an amount of about 1% to about 60% by weight of the drug-ion exchange resin complex and the diffusion barrier comprises a water-permeable film-forming polymer and contains no substantial traces of an organic solvent.

23. The method of claim 22, wherein the water-permeable film-forming polymer is ethylcellulose.

24. The method of claim 22, wherein the diffusion barrier coated drug-ion exchange resin complex includes a solvating agent.

25. The method of claim 24, wherein the solvating agent is polyethylene glycol.

26. The method of claim 22, wherein the drug is released in vivo over a period of about 4 hours.

27. The method of claim 22, wherein the drug is released in vivo over a period of about 12 hours.

28. The method of claim 22, wherein the drug is released in vivo over a period of 24 hours.

29. The method of claim 22, wherein the ion exchange resin has a particle size from about 30 microns to about 500 microns.

30. The method of claim 22, wherein the ion exchange resin has a particle size from about 40 microns to about 150 microns.

31. The method of claim 22, wherein the composition is a liquid.

32. A drug particle suitable for forming a sustained release oral pharmaceutical composition comprising a drug-ion exchange resin complex, a solvating agent, and a water-permeable diffusion barrier surrounding at least a portion of the drug-ion exchange resin complex;

wherein the diffusion barrier comprises a film-forming polymer and is free or substantially free of traces of organic solvents.

33. A sustained release oral pharmaceutical composition comprising the drug particle of claim 32.

34. An oral pharmaceutical composition comprising ion exchange resin particles having particle sizes from 30 microns to about 500 microns;

at least one pharmaceutically active drug releasably bound to the particles to form a drug-ion exchange resin complex, wherein the drug-ion exchange resin complex is coated with an aqueous based diffusion barrier which comprises from about 1% to about 60%, by weight of the resin particles, of a water-permeable film-forming polymer.