ALCOHOL-RESISTANT ORAL PHARMACEUTICAL FORM

• US 20130059010A1
• Filed: 05/14/2010
• Published: 03/07/2013
• Est. Priority Date: 05/14/2010
• Status: Abandoned Application

• Current Assignee: ETHYPHARM
• Original Assignee: ETHYPHARM
• Inventors: Herry, Catherine, Trichard, Laury
• Application Number:
  US13/697,947
• Publication Number:
  US 20130059010A1
• Time in Patent Office: Days
• US Class Current: 424/495
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

A sustained release oral pharmaceutical form suitable for single daily dose administration has a neutral microgranule coated with a mounting layer of active ingredient and pharmaceutically acceptable binder; and a coating layer of a hydrophobic coating polymer of a non-water soluble cellulose derivative, and at least 20% of inert load in relation to dry weight of hydrophobic coating polymer. The pharmaceutical form has improved resistance to rapid release of active ingredient, particularly in the presence of alcohol.

Claims

1-16. -16. (canceled)

17. Sustained release microgranules comprising:

a neutral carrier,

at least one mounting layer comprising at least one active ingredient and a pharmaceutically acceptable binder,

at least one sustained-release coating layer comprising;

a hydrophobic coating polymer selected from non-water soluble cellulose derivatives,

at least 20% of an inert load in relation to the dry weight of the hydrophobic coating polymer.

18. The microgranules of claim 17, wherein the inert load is selected from the group consisting of:

talc, magnesium stearate, glycerol monostearate, silica, magnesium silicate, aluminum silicate, magnesium stearyl fumarate and mixtures thereof.

19. The microgranules of claim 17, wherein the hydrophobic coating polymer is selected from the group consisting of ethylcellulose, cellulose acetate butyrate, cellulose acetate and mixtures thereof.

20. The microgranules of claim 17, wherein the quantity of the hydrophobic coating polymer is from 30% to 80%, preferably from 50% to 80%, of the dry weight of said coating layer.

21. The microgranules of claim 17, wherein the pharmaceutically acceptable binder is selected from cellulose derivatives, polyvinylpyrrolidone derivatives, and polyethylene glycol derivatives, vinyl derivatives, and mixtures thereof.

22. The microgranules of claim 17, further comprising a plasticizer in the coating layer.

23. The microgranules of claim 17, further comprising a surfactant in the coating layer.

24. The microgranules of claim 17, wherein the active ingredient is selected from hormones, active ingredients that act on the central nervous system, active ingredients that act on the cardiovascular system, antibiotics, antivirals and analgesics.

25. The microgranules of claim 17, wherein the active ingredient is selected from analgesics and notably non-opiate, weak opiate, mixed opioid, morphine or spasmodic analgesics, notably hydrocodone, hydromorphone, morphine, oxycodone, oxymorphone, tramadol, gabapentin and derivatives thereof.

26. The microgranules of claim 24, wherein the active ingredient is morphine and/or derivatives thereof.

27. The microgranules of claim 17, further comprising at least one pre-mounting layer between the neutral carrier and the mounting layer, said pre-mounting layer comprising at least one hydrophobic polymer, an inert load, optionally a plasticizer and/or a surfactant.

28. The microgranules of claim 17, wherein the plasticizer is selected from:

acetylated glycerides, glyceryl monostearate, glyceryl triacetate, glyceryl tributyrate, phthalates, dibutyl phthalate, diethyl phthalate, dimethyl phthalate, dioctyl phthalate, citrates, acetyl tributyl citrate, acetyl triethyl citrate, tributyl citrate, triethyl citrate, sebacates, diethyl sebacate, dibutyl sebacate, adipates, azelates, benzoates, chlorobutanols, polyethylene glycols, plant oils, fumarates, diethyl fumarate, malates, diethyl malate, oxalates, diethyl oxalate, succinates, dibutyl succinate, butyrates, cetyl alcohol esters, malonates, diethyl malonate, castor oil and mixtures thereof.

29. Sustained release oral pharmaceutical form comprising a plurality of the microgranules of claim 17 and wherein the pharmaceutical form possesses alcohol-resistance.

30. Use of the microgranules of claim 17 to avoid or limit an immediate release of the active ingredient induced by the consumption of alcohol.

31. The pharmaceutical form of claim 29 for its use as a drug administered orally once a day or twice a day.

32. A method for preparing the microgranules of claim 17 comprising the following steps:

introduction of spherical neutral carriers that are soluble, insoluble or rendered insoluble in a fluid bed reactor,

spraying on these spherical neutral carriers of at least one active ingredient in solution or in suspension in an organic and/or aqueous solvent optionally supplemented with at least one pharmaceutically acceptable binder,

spraying of a coating suspension comprising at least one hydrophobic polymer and an inert load on the mounted particles obtained in the preceding step,

eventually, drying of the medicinal microgranules thus obtained.