Methods of Treating PDNV and PONV with Extended Release Ondansetron Compositions

• US 20110003005A1
• Filed: 01/15/2010
• Published: 01/06/2011
• Est. Priority Date: 07/06/2009
• Status: Abandoned Application

• Current Assignee: Aptalis Pharmatech Incorporated
• Original Assignee: Aptalis Pharmatech Incorporated
• Inventors: Perrett, Stephen, Thieroff-Ekerdt, Ruth, Venkatesh, Gopi
• Application Number:
  US12/688,493
• Publication Number:
  US 20110003005A1
• Time in Patent Office: Days
• US Class Current: 424/494
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Extended release ondansetron compositions of the present invention are useful for treating postoperative nausea and vomiting (PONV) and/or postdischarge nausea and vomiting (PDNV).

Claims

1. A method of treating or preventing PONV or PDNV comprising orally administering to a surgical patient in need thereof, at least one extended release dosage form comprising a selective serotonin 5-HT₃ antagonist, prior to and/or after surgery.

2. The method of claim 1, wherein the extended release dosage form comprises TPR particles and IR particles;

the TPR particles each comprise a core coated with a TPR layer;

the core comprises a selective serotonin 5-HT₃ antagonist and a pharmaceutically acceptable organic acid, wherein the selective serotonin 5-HT₃ antagonist and the pharmaceutically acceptable organic acid are separated from each other by an SR layer;

the TPR layer comprises a water insoluble polymer and an enteric polymer;

the SR layer comprises a water insoluble polymer; and

the IR particles each comprise the selective serotonin 5-HT₃ antagonist, and release at least about 80 wt. % of the selective serotonin 5-HT₃ antagonist in about 5 minutes when dissolution tested using United States Pharmacopoeia dissolution methodology (Apparatus 2—

paddles@ 50 RPM, 0.1N HCl at 37°

C.

3. The method of claim 1, wherein the selective serotonin 5-HT₃ antagonist is selected from the group consisting of ondansetron, tropisetron, granisetron, dolasetron, palonosetron, ramosetron, and salts and/or solvates thereof.

4. The method of claim 1, wherein the selective serotonin 5-HT₃ antagonist is ondansetron, and salts and/or solvates thereof.

5. The method of claim 2, wherein:

the water-insoluble polymer of the TPR and SR layers is independently selected from the group consisting of ethyl cellulose, cellulose acetate, polyvinyl acetate, neutral copolymers of ethyl acrylate and methylmethacrylate, copolymers of acrylic and methacrylic esters containing quaternary ammonium groups, and waxes;

the enteric polymer is selected from the group consisting of cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, polyvinyl acetate phthalate, pH-sensitive copolymers of methacrylic acid and methylmethacrylate, and shellac; and

the pharmaceutically acceptable organic acid is selected from the group consisting of citric acid, lactic acid, fumaric acid, malic acid, maleic acid, tartaric acid, succinic acid, oxalic acid, aspartic acid, and glutamic acid.

6. The method of claim 5, wherein the TPR and/or SR layers each independently further comprise a pharmaceutically acceptable plasticizer.

7. The method of claim 6, wherein the pharmaceutically acceptable plasticizer of the TPR and/or SR layer(s) is independently selected from the group consisting of triacetin, tributyl citrate, triethyl citrate, acetyl tri-n-butyl citrate, diethyl phthalate, dibutyl sebacate, polyethylene glycol, polypropylene glycol, castor oil, acetylated mono- and di-glycerides and mixtures thereof.

8. The method of claim 2, wherein the TPR particles each comprise:

an inert bead;

an acid layer disposed over the inert bead, comprising the pharmaceutically acceptable organic acid;

the SR layer disposed over the acid layer;

a drug layer disposed over the SR layer, wherein the drug layer comprises the selective serotonin 5-HT₃ antagonist; and

the TPR layer disposed over the drug layer.

9. The method of claim 8, wherein the inert bead has an average particle size of 25-30 mesh and is selected from the group consisting of sugar spheres, cellulose spheres, lactose spheres, lactose-MCC spheres, mannitol-MCC spheres, and silicone dioxide spheres.

10. The method of claim 9, wherein:

the acid layer comprises fumaric acid;

the SR layer comprises ethylcellulose;

the drug layer comprises ondansetron or a pharmaceutically acceptable salt or solvate thereof; and

the TPR layer comprises ethyl cellulose and hydroxypropylmethylcellulose phthalate.

11. The method of claim 2, wherein the IR particles further comprise a pharmaceutically acceptable organic acid, and the pharmaceutically acceptable organic acid of the IR and TPR particles are the same or different.

12. The method of claim 11, wherein the IR particles are a granulate comprising the pharmaceutically acceptable organic acid, the selective serotonin 5-HT₃ antagonist, and an optional binder.

13. The method of claim 12, wherein the IR particles are a granulate comprising fumaric acid, ondansetron or pharmaceutically acceptable salts and/or solvates thereof, and a binder.

14. The method of claim 10, wherein the IR particles are a granulate comprising fumaric acid, ondansetron or pharmaceutically acceptable salts and/or solvates thereof, and a binder.

15. The method of claim 14, wherein the extended release dosage form is a capsule comprising a therapeutically effective amount of the TPR particles and IR particles, whereby the capsule contains a total amount of ondansetron or pharmaceutically acceptable salts and/or solvates thereof equivalent to 24 mg of ondansetron.

16. The method of claim 1, wherein said administering comprises administering the extended release dosage form prior to surgery, whereby PONV and/or PDNV are ameliorated or prevented.

17. The method of claim 15, wherein said administering comprises administering the extended release dosage form prior to surgery, whereby PONV and/or PDNV are ameliorated or prevented.

18. The method of claim 1, wherein said administering comprises administering the extended release dosage form after surgery and at discharge, whereby PDNV is ameliorated or prevented.

19. The method of claim 15, wherein said administering comprises administering the extended release dosage form after surgery and at discharge, whereby PDNV is ameliorated or prevented.

20. The method of claim 1, wherein said administering comprises administering the extended release dosage form after discharge, whereby PDNV is ameliorated or prevented.

21. The method of claim 15, wherein said administering comprises administering the extended release dosage form after discharge, whereby PDNV is ameliorated or prevented.

22. The method of claim 18, further comprising administering at least one additional extended release dosage form once daily after discharge.

23. The method of claim 19, further comprising administering at least one additional extended release dosage form once daily after discharge.

24. The method of claim 18, further comprising administering at least one additional extended release dosage form in the morning following discharge, and optionally once-daily for up to 4 additional days.

25. The method of claim 19, further comprising administering at least one additional extended release dosage form in the morning following discharge, and optionally once-daily for up to 4 additional days.

26. The method of claim 1, further comprising administering an intravenous antiemetic before or immediately after surgery.

27. The method of claim 1, wherein the patient is at moderate or increased risk of PONV or PDNV.

28. The method of claim 16, wherein the patient is at moderate or increased risk of PONV or PDNV

29. The method of claim 27, and wherein the patient meets one or more of the following criteria:

(a) female;

(b) prior history of PONV and/or motion sickness;

(c) nonsmoker

(d) the patient has had outpatient surgery;

(e) the patient has had outpatient surgery having a duration of at least 60 min.;

(f) the patient has had general anesthesia which is balanced inhalational anesthesia.

(g) the patient has had nitrous oxide anesthesia;

(h) the patient has been administered intraoperative or post operative opioids; and

(i) the patient has had a surgery selected from the group consisting of laparoscopy, ear-nose-throat, neurosurgery, breast surgery, strabismus surgery, laparotomy, and plastic surgery.

30. The method of claim 1, wherein the surgical patient is treated with opioid analgesics after surgery.

31. The method of claim 30, wherein the opioid is selected from the group consisting of codeine, morphine, thebaine, oripavine, diacetyl morphine, dihydrocodeine, hydrocodone, hydromorphone, nicomorphine, oxycodone, oxymorphone, fentanyl, α

-methyl fentanyl, alfentanil, sufentanil, remifentanil, meperidine, buprenorphine, etorphine, methadone, and tramadol.

32. The method of claim 15, wherein the surgical patient is treated with opioid analgesics after surgery.

33. The method of claim 32, wherein the opioid is selected from the group consisting of codeine, morphine, thebaine, oripavine, diacetyl morphine, dihydrocodeine, hydrocodone, hydromorphone, nicomorphine, oxycodone, oxymorphone, fentanyl, α

-methyl fentanyl, alfentanil, sufentanil, remifentanil, meperidine, buprenorphine, etorphine, methadone, and tramadol.

34. The method of claim 1, further comprising administering at least one additional oral antiemetic.

35. The method of claim 34, wherein the additional oral antiemetic is selected from the group consisting of NK-1 antagonists, dopamine antagonists, H1 histamine receptor antagonists, cannabinoids, benzodiazepines, anticholinergics, and steroids.

36. The method of claim 35, wherein the NK-1 antagonist is selected from the group consisting of aprepitant and casopitant;

the dopamine antagonist is selected from the group consisting of domperidone, droperidol, haloperidol, chlorpromazine, and prochlorperazine;

the H1 histamine receptor antagonist is selected from the group consisting of cyclizine, diphenhydramine, dimenhydrinate, meclizine, promethazine, and hydroxyzine;

the cannabinoid is selected from the group consisting of cannabis, dronabinol, and nabilone;

the benzodiazepine is selected from the group consisting of midazolam and lorazepam;

the anticholinergic is scopalamine; and

the steroid is dexamethasone.

37. The method of claim 15, further comprising administering at least one additional oral antiemetic.

38. The method of claim 37, wherein the additional oral antiemetic is selected from the group consisting of NK-1 antagonists, dopamine antagonists, H1 histamine receptor antagonists, cannabinoids, benzodiazepines, anticholinergics, and steroids.

39. The method of claim 38, wherein the NK-1 antagonist is selected from the group consisting of aprepitant and casopitant;

the dopamine antagonist is selected from the group consisting of domperidone, droperidol, haloperidol, chlorpromazine, and prochlorperazine;

the H1 histamine receptor antagonist is selected from the group consisting of cyclizine, diphenhydramine, dimenhydrinate, meclizine, promethazine, and hydroxyzine;

the cannabinoid is selected from the group consisting of cannabis, dronabinol, and nabilone;

the benzodiazepine is selected from the group consisting of midazolam and lorazepam;

the anticholinergic is scopalamine; and

the steroid is dexamethasone.