Nova Patents
EP1998754A2

Stable lozenge compositions providing rapid release of nicotine

Abstract

This record has no abstract on file.

Term

Projected expiry 16 March 2027.

  1. Priority
  2. Filed
  3. Published
  4. Today
  5. Projected expiry

51 claims: 38 independent, 13 dependent

  1. 1
    Claims of equivalent WO 2007104575 A2 Claims 1. Use of a nicotine-cellulose combination and one or more pharmaceutically acceptable excipients for the preparation of a lozenge composition for achievement of a fast onset of action of nicotine after application of the solid dosage form to the oral cavity of a subject.
  2. 2
    Use according to claim, wherein the composition has a shelf-life of 24 months or more when stored protected from light at a temperature not exceeding 25 0 C.
  3. 4
    Use according to any of the preceding claims, wherein the composition - when subjected to an in vitro dissolution test as described herein - within the first 2 minutes after start of the test releases nicotine with a release rate corresponding to 7.5 % w/w or more of the total content in the composition per minute.
  4. 6
    Use according to any of the preceding claims, wherein said release rate within the first 2 minutes after start of the test is 17% w/w or more such as, e.g., 18% w/w or more, 19% w/w or more, 20% w/w or more, 21% or more, 22% or more, 23% or more, 24% or more or 25% w/w or more of the total content of nicotine in the composition per minute.
  5. 7
    Use according to any of the preceding claims, wherein at least 65% w/w such as, e.g., at least 70% w/w of the total content of nicotine in the composition is released within 5 minutes when subjecting the composition to an in vitro release test.
  6. 8
    Use according to any of the preceding claims, wherein at least 75% w/w such as, e.g., at least 85% w/w of the total content of nicotine in the composition is released within 10 minutes when subjecting the composition to an in vitro release test.
  7. 9
    Use according to any of the preceding claims, wherein onset of a nicotine effect is at the most 5 minutes such as at the most 2.5 minutes after administration of the composition to a subject.
  8. 10
    Use according to any of the preceding claims, wherein the cellulose of the nicotine- cellulose combination comprises internal voids and/or pores.
  9. 12
    Use according to any of the preceding claims, wherein the cellulose is a cellulose derived from a plant, an algae, a bacterium, a fungi, or combinations thereof
  10. 13
    Use according to any of the preceding claims, wherein the cellulose has a surface area of at least 0.7 m 2 /g.
  11. 14
    Use according to any of the preceding claims, wherein the cellulose is a crystalline cellulose including a microcrystalline cellulose.
  12. 15
    Use according to any of the preceding claims, wherein said cellulose is a microcrystalline cellulose, which is selected from the group consisting of AVICEL® grades PH-100, PH-102, PH-103, PH-105, PH-112, PH-113, PH-200, PH-300, PH-302, VIVACEL® grades 101 , 102, 12, 20 and EMOCEL® grades 5OM and 9OM, and the like, and mixtures thereof.
  13. 17
    Use according to any of the preceding claims, wherein the mean particle size of the cellulose is in a range of from about 15 to about 250 μm.
  14. 18
    Use according to any of the preceding claims, wherein nicotine is at least partly sorbed on the cellulose.
  15. 19
    Use composition according to any of the preceding claims, wherein the concentration of the nicotine-cellulose combination in the composition is at least about 2% w/w such as in a range from about 2% w/w to about 98% w/w, from about 2% to about 96% w/w, from about 2% w/w to about 95% w/w, from about 3 % w/w to about 90% w/w, from about 4 % w/w to about 85% w/w, from about 5 % w/w to about 80% w/w, from about 5 % w/w to about 75% w/w, from about 5 % w/w to about 70% w/w, or from about 7.5% w/w to about 65% w/w.
  16. 20
    Use according to any of the preceding claims, wherein the concentration of the nicotine-cellulose combination in the composition is from about 2 % w/w to about 20% w/w such as, e.g., from about 4% w/w to about 19% w/w, from about 5% w/w to about 18% w/w, from about 6% w/w to about 17% w/w, from about 7% w/w to about 16% w/w or from about 8% w/w to about 15% w/w.
  17. 21
    Use according to any of the preceding claims, wherein the concentration of nicotine in the composition is at least about 0.01% w/w such as in a range from about 0.05 to about 75% w/w, from about 0.1 to about 70% w/w, from about 0.3 to about 70% w/w, from about 0.4 to about 50% w/w, from about 0.1 % w/w to about 50% w/w, from about 0.5% w/w to about 45% w/w, from about 1.0% w/w to about 40% w/w, from about 1.5% w/w to about 35% w/w, from about 2% w/w to about 30% w/w, from about 2.5 % w/w to about 25% w/w, from about 2.5 % w/w to about 20% w/w, from about 3% w/w to about 15% w/w.
  18. 22
    Use according to any of the preceding claims, wherein the concentration of nicotine in the composition is in a range from about 0.1% w/w to about 15% w/w such as, e.g., from about 0.1% w/w to about 14% w/w, from about 0.1% w/w to about 13% w/w, from about 0.1 % w/w to about 12% w/w, from about 0.1 % w/w to about 11 % w/w, from about 0.1% w/w to about 10% w/w as calculated as free nicotine base.
  19. 23
    Use according to any of the preceding claims, wherein said nicotine is present in a concentration from about 0.1% w/w to about 90% w/w.
  20. 24
    Use according to any of the preceding claims, wherein the composition has a nicotine content of from about 0.5 mg to about 10 mg such as, e.g., from about 1 mg to about 8 mg, from about 1.5 mg to about 7.5 mg, from about 2 mg to about 5 mg, from about 2.5 mg to about 5 mg, from about 3 to about 10 mg, from about 3 to about 7.5 mg or from about 3 mg to about 5 mg such as, e.g., about 1.5 mg, about 2 mg, about 2.5 mg, about 3 mg, about 3.5 mg, about 4 mg, about 5 mg or about 6 mg, as calculated as free nicotine base.
  21. 25
    Use according to any of the preceding claims, wherein the composition comprises 1.25 mg of nicotine calculated as free nicotine base.
  22. 26
    Use according to any of claims 1-24, wherein the composition comprises 2.5 mg of nicotine calculated as free nicotine base.
  23. 27
    Use according to any of claims 1-24, wherein the composition comprises 5 mg of nicotine calculated as free nicotine base.
  24. 28
    Use according to any of the preceding claims, wherein said nicotine is selected from the group consisting of nicotine base, nicotine hydrochloride, nicotine dihydrochloride, nicotine monotartrate, nicotine bitartrate, nicotine sulfate, nicotine zinc chloride such as nicotine zinc chloride monohydrate and nicotine salicylate.
  25. 29
    Use according to any of the preceding claims, wherein nicotine in the nicotine- cellulose combination is in its free base form.
  26. 30
    Use according to any of the preceding claims, wherein the composition further comprises one or more buffering agents.
  27. 34
    Use according to any of the preceding claims, wherein the composition further comprising one or more sweeteners, such as sugar alcohols including xylitol, sorbitol, maltitol and/or isomalt, or artificial sweeteners such as e.g. aspartame, acesulfame or saccharin.
  28. 36
    Use according to any of the preceding claims, wherein the composition further comprises one or more anti-oxidants, such as, e.g., ascorbyl palmitate, sodium ascorbate, ascorbic acid, butylated hydroxyanisole, butylated hydroxytoluene, betacarotenes, tocopherols, propyl gallate.
  29. 39
    Use according to any of the preceding claims, wherein the composition comprises one or more flavouring agents, such as, e.g., menthol flavour, eucalyptus, mint flavour and/or L-menthol.
  30. 41
    Use according to any of the preceding claims, wherein the concentration of nicotine of a pharmaceutically acceptable salt, solvate or complex in the nicotine-cellulose combination is at the most 70% w/w such as, e.g., at the most 60% w/w, at the most 50% w/w, at the most 45% w/w, at the most about 40% w/w, at the most about 35% w/w, at the most about 30% w/w, at the most about 25% w/w, at the most about 20% w/w, at the most about 15% w/w, at the most about 12.5% w/w, at the most about 10% w/w, at the most about 9.5% w/w, at the most about 9% w/w, at the most about 8.5% w/w or at the most about 8% w/w, and the concentration being calculated as the nicotine base.
  31. 42
    Use according to any of the preceding claims, wherein the concentration of nicotine in the nicotine-cellulose combination is from about 3 % w/w to about 20% w/w, such as, e.g., from about 4% w/w to about 19% w/w, from about 5% w/w to about 18% w/w, from about 6% w/w to about 17% w/w, from about 7% w/w to about 16% w/w or from about 8% w/w to about 15% w/w.
  32. 43
    Use according to any of the preceding claims, wherein the composition comprises a pharmaceutically acceptable excipient such as, e.g. a filler, a binder, a lubricant, a glidant, an anti-adhesive, a buffering agent, a stabilizing agent, a pH adjusting agent, a preservative, a coloring agent, a flavoring agent, a taste-masking agent, a sweetener etc.
  33. 46
    Use according to any of claims 43-45, wherein the composition comprises magnesium stearate in a concentration from about 0.1% w/w to about 5% w/w, such as, e.g., from about 0.2% w/w to about 4% w/w, from about 0.3% w/w to about 3.5% w/w or from about 0.5% w/w to about 3% w/w.
  34. 47
    Use according to any of claims 43-46, wherein the composition comprises silica in a concentration from about 0.1% w/w to about 4% w/w, such as, e.g., from about 0.2% w/w to about 3% w/w, from about 0.3% w/w to about 2% w/w or from about 0.4% w/w to about 1.5% w/w.
  35. 48
    Use according to any of the preceding claims, wherein the composition after administration to a subject has a relative bioavailability as calculated by AUC 0 - ιn finιty (tested composition)/AUC 0 -infinity (Nicorette®) x 100 % of at least 120% such as, e.g., at least about 130%, at least about 140% or about 150% - provided that the composition and Nicorette® contains the same amount of nicotine calculated as free base.
  36. 49
    Use according to any of the preceding claims, for treatment and/or prophylaxis of nicotine addiction.
  37. 50
    A composition comprising a nicotine-cellulose combination and one or more pharmaceutically acceptable excipients as defined in any of claims 1-49.
  38. 51
    A method for preparation of a composition defined in any of claims 1-50 comprising mixing a nicotine-cellulose combination with one or more pharmaceutical acceptable excipients and forming the resulting mixture it into a tablet by compression.
Independent claims38