Pharmaceutical compositions

• US 9,498,444 B2
• Filed: 07/01/2015
• Issued: 11/22/2016
• Est. Priority Date: 01/09/2008
• Status: Active Grant

• Current Assignee: LOCL Pharma, Inc. (Charleston Laboratories, Inc.)
• Original Assignee: LOCL Pharma, Inc. (Charleston Laboratories, Inc.)
• Inventors: Bosse, Paul, Ameling, John, Schachtel, Bernard, Takigiku, Ray
• Primary Examiner(s): TRAN, SUSAN T
• Application Number:
  US14/789,886
• Publication Number:
  US 20150297525A1
• Time in Patent Office: 510 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/24 having an amino or nitro group
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/422 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/515 Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 : Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2086 : Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/209 : containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/4808 : characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/5084 : Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 1/08 : for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 29/02 : without antiinflammatory effect
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

Methods and compositions are provided which comprise effective amounts of analgesic to treat a subject, including reducing or eliminating an adverse effect associated with the analgesic.

Claims

1. A method for treating pain, and reducing or preventing opioid-induced nausea or vomiting, the method comprising administering a solid oral pharmaceutical composition to a subject in need thereof, wherein the solid oral pharmaceutical composition comprises:

an immediate-release matrix comprising an antiemetic; and

a controlled-release matrix comprising an opioid analgesic and a non-opioid analgesic, wherein the solid oral pharmaceutical composition demonstrates the following dissolution profile;

wherein about 90% of the antiemetic is released in about 1 minute to about 20 minutes following contact of the solid oral pharmaceutical composition with a dissolution fluid as measured by a USP Apparatus 2 (Paddle Apparatus), wherein about 30% to about 60% of the opioid analgesic is released in about 5 to 10 minutes following contact of the solid oral pharmaceutical composition with a dissolution fluid as measured by a USP Apparatus 2 (Paddle Apparatus), and wherein about 100% of the opioid analgesic is released in about 60 minutes following contact of the solid oral pharmaceutical composition with a dissolution fluid as measured by a USP Apparatus 2 (Paddle Apparatus), and

wherein the solid oral pharmaceutical composition provides an effective amount of the opioid analgesic and the non-opioid analgesic to treat pain, and wherein the solid oral pharmaceutical composition provides an effective amount of the antiemetic to reduce or prevent nausea associated with the opioid analgesic or vomiting associated with the opioid analgesic.

2. The method of claim 1, wherein the opioid analgesic is hydrocodone, oxycodone, acetyldihydrocodeinone, diamorphine, codeine, pethidine, alfentanil, buprenorphine, butorphanol, codeine, dezocine, fentanyl, hydromorphone, levomethadyl acetate, levorphanol, meperidine, methadone, morphine sulfate, nalbuphine, oxymorphone, pentazocine, propoxyphene, remifentanil, sufentanil, tramadol, or a pharmaceutically acceptable salt thereof.

3. The method of claim 1, wherein the opioid analgesic is present in an amount of about 5 mg, about 7.5 mg, about 10 mg, about 15 mg, about 20 mg, or about 30 mg.

4. The method of claim 2, wherein the opioid analgesic is hydrocodone bitartrate.

5. The method of claim 1, wherein the opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof, and is present in an amount of about 7.5 mg.

6. The method of claim 5, wherein the pharmaceutically acceptable salt of the hydrocodone is hydrocodone bitartrate, and is present in an amount of about 7.5 mg.

7. The method of claim 1, wherein the opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof, and is present in an amount of about 5 mg or about 10 mg.

8. The method of claim 3, wherein the opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof, or oxycodone or a pharmaceutically acceptable salt thereof.

9. The method of claim 8, wherein the opioid analgesic is oxycodone or the pharmaceutically acceptable salt thereof, and is present in an amount of about 7.5 mg.

10. The method of claim 8, wherein the opioid analgesic is oxycodone or the pharmaceutically acceptable salt thereof, and is present in an amount of about 5 mg.

11. The method of claim 2, wherein the opioid analgesic is a pharmaceutically acceptable salt of oxycodone that is oxycodone hydrochloride.

12. The method of claim 1, wherein the antiemetic is promethazine or a pharmaceutically acceptable salt thereof.

13. The method of claim 12, wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount of about 11-14 mg.

14. The method of claim 13, wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount of about 12.5 mg.

15. The method of claim 14, wherein the pharmaceutically acceptable salt of the promethazine is promethazine hydrochloride, and is present in an amount of about 12.5 mg.

16. The method of claim 13, wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount of about 11 mg.

17. The method of claim 12, wherein the antiemetic is the pharmaceutically acceptable salt of the promethazine that is promethazine hydrochloride.

18. The method of claim 1, wherein the non-opioid analgesic is acetaminophen or a pharmaceutically acceptable salt thereof.

19. The method of claim 18, wherein the acetaminophen or the pharmaceutically acceptable salt thereof is present in an amount of about 290-360 mg.

20. The method of claim 19, wherein the acetaminophen or the pharmaceutically acceptable salt thereof is present in an amount of about 325 mg.

21. The method of claim 1, wherein the antiemetic is present in an amount of about 0.5 mg to about 60 mg.

22. The method of claim 1 or 21, wherein the antiemetic is aprepitant, dronabinol, perphenazine, palonosetron, trimethyobenzamide, metoclopromide, domperidone, prochlorperazine, promethazine, chlorpromazine, trimethobenzamide, ondansetron, granisetron, hydroxyzine, acetylleucine monoethanolamine, alizapride, azasetron, benzquinamide, bietanautine, bromopride, buclizine, clebopride, cyclizine, dimenhydrinate, diphenidol, dolasetron, meclizine, methallatal, metopimazine, nabilone, oxyperndyl, pipamazine, scopolamine, sulpiride, tetrahydrocannabinol, thiethylperazine, thioproperazine, tropisetron, droperidol, haloperidol, prochloperazine, metoclopramide, diphenhydramine, cannabis, midazolam, lorazepam, hyoscine, dexamethasone, emetrol, propofol, or a pharmaceutically acceptable salt thereof.

23. The method of claim 21, wherein the antiemetic is promethazine or a pharmaceutically acceptable salt thereof, and is present in an amount of about 12.5 mg, about 25 mg, or about 50 mg.

24. The method of claim 1, wherein the non-opioid analgesic is present in an amount of about 200 mg to about 1000 mg.

25. The method of claim 24, wherein the non-opioid analgesic is acetaminophen, ibuprofen, ketaprofen, naproxen, aspirin, or a pharmaceutically acceptable salt thereof.

26. The method of claim 1, wherein the immediate-release matrix is a first layer and the controlled-release matrix is a second layer.

27. The method of any one of claim 1-17, 18-20, 21, or 23-26, wherein the solid oral pharmaceutical composition is a tablet.

28. The method of claim 27, wherein the tablet has a thickness of about 6.5 mm or a hardness of about 15 kp.

29. The method of claim 27, wherein the tablet is a bi-layer tablet.

30. The method of claim 1, wherein the solid oral pharmaceutical composition provides an effective amount of the antiemetic to reduce or prevent nausea associated with the opioid analgesic or vomiting associated with the opioid analgesic for about 4 to about 6 hours, and an effective amount of the opioid analgesic and the non-opioid analgesic to treat pain for about 4 to about 6 hours.

31. The method of claim 1, wherein the opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof, wherein the non-opioid analgesic is acetaminophen or a pharmaceutically acceptable salt thereof, and wherein the antiemetic is promethazine or a pharmaceutically acceptable salt thereof.

32. The method of claim 7, wherein the pharmaceutically acceptable salt of the hydrocodone is hydrocodone bitartrate, and is present in an amount of about 5 mg or about 10 mg.

33. The method of claim 1, wherein the solid oral pharmaceutical composition further comprises an opioid antagonist or an abuse deterrent agent.