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EP-4543417-B1 - ORALLY DISINTEGRATING NICOTINE TABLET FOR USE UNDER LIP

EP4543417B1EP 4543417 B1EP4543417 B1EP 4543417B1EP-4543417-B1

Inventors

  • NIELSEN, KENT ALBIN
  • NIELSEN, BRUNO PROVSTGAARD
  • MARTINUSSEN, Helle

Dates

Publication Date
20260513
Application Date
20240318

Claims (20)

  1. An orally disintegrating nicotine tablet for use in alleviation of nicotine craving, the tablet comprising nicotine and a pH regulating agent, wherein the tablet is administered between the lip and gum.
  2. The orally disintegrating nicotine tablet for use according to claim 1, wherein the tablet is administered between the upper lip and gum.
  3. The orally disintegrating nicotine tablet for use according to claim 1 or 2, wherein the tablet is designed to disintegrate within a period of 300 seconds upon oral administration between the lip and gum, such as within 270 seconds upon oral administration between the lip and gum, such as within 240 seconds upon oral administration, such as within a period of 210 seconds upon oral administration, such as within a period of 180 seconds upon oral administration, such as within a period of 150 seconds upon oral administration, such as within a period of 120 seconds upon oral administration, such as within a period of 90 seconds upon oral administration, such as within a period of 60 seconds upon oral administration.
  4. The orally disintegrating nicotine tablet for use according to any of claims 1-3, wherein the tablet is a compressed orally disintegrating nicotine tablet.
  5. The orally disintegrating nicotine tablet for use according to any of claims 1-4, wherein the tablet comprises at least one sugar alcohol.
  6. The orally disintegrating nicotine tablet for use according to any of claims 1-5, wherein the tablet comprises the at least one sugar alcohol sugar alcohol in an amount of at least 40% by weight of the tablet, such as at least 50% by weight of the tablet, such as at least 60% by weight of the tablet, such as at least 70% by weight of the tablet, such as at least 80% by weight of the tablet.
  7. The orally disintegrating nicotine tablet for use according to any of claims 1-6, wherein the at least one sugar alcohol comprises sugar alcohol selected from the group consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol and any combination thereof.
  8. The orally disintegrating nicotine tablet for use according to any of claims 1-7, wherein the tablet further comprises a disintegrant.
  9. The orally disintegrating nicotine tablet for use according to any of claims 1-8, wherein the tablet comprises disintegrant in an amount of at least 0.5% by weight of the tablet, such as at least 1% by weight of the tablet, such as at least 2% by weight of the tablet, such as at least 3% by weight of the tablet, such as at least 5% by weight of the tablet.
  10. The orally disintegrating nicotine tablet for use according to any of claims 1-9, wherein the disintegrant is selected from the list consisting of starch, pregelatinated starch, modified cellulose, alginates, ion-exchange resin, calcium silicate, crosslinked cellulose, crosslinked polyvinyl pyrrolidone, crosslinked starch, crosslinked alginic acid, and combinations thereof.
  11. The orally disintegrating nicotine tablet for use according to any of claims 1-10, wherein the disintegrant comprises a superdisintegrant.
  12. The orally disintegrating nicotine tablet for use according to claim 11, wherein the superdisintegrant is selected from the group consisting of crosslinked cellulose, crosslinked polyvinyl pyrrolidone, crosslinked starch, crosslinked alginic acid, and any combinations thereof.
  13. The orally disintegrating nicotine tablet for use according to any of claims 1-12, wherein the nicotine is selected from the group consisting of a nicotine salt, nicotine free base, a nicotine-ion exchange resin combination, a nicotine inclusion complex or nicotine in any non-covalent binding, nicotine bound to zeolites, nicotine bound to cellulose, nicotine bound to starch microspheres, and any combination thereof.
  14. The orally disintegrating nicotine tablet for use according to any of claims 1-13, wherein the nicotine comprises nicotine salt, such as nicotine bitartrate.
  15. The orally disintegrating nicotine tablet for use according to any of claims 1-14, wherein the tablet comprises nicotine in an amount of at least 0.2 mg, such as at least 0.5 mg, such as at least 1.0 mg.
  16. The orally disintegrating nicotine tablet for use according to any of claims 1-15, wherein the pH regulating agent is an alkaline pH regulating agent, such as an alkaline buffering agent.
  17. The orally disintegrating nicotine tablet for use according to any of claims 1-16, wherein the tablet has a weight of no more than 600 mg, such as no more than 500 mg, such as no more than 400 mg, such as no more than 300 mg, such as no more than 200 mg, such as no more than 150 mg, such as no more than 120 mg, such as no more than 100 mg.
  18. The orally disintegrating nicotine tablet for use according to any of claims 1-17, wherein the tablet comprises flavor.
  19. The orally disintegrating nicotine tablet for use according to any of claims 1-18, wherein the maximum plasma concentration (Cmax) of nicotine is increased by administration between the lip and gum compared to administration on the tongue.
  20. The orally disintegrating nicotine tablet for use according to any of claims 1-19, wherein the maximum plasma concentration (Cmax) of nicotine is increased by administration between the lip and gum compared to sublingual administration.

Description

FIELD OF INVENTION The invention relates to an orally disintegrating nicotine tablet for use in alleviation of nicotine craving according to the claims. BACKGROUND Nicotine-releasing tablets applied for the purpose of providing a release of nicotine in a user's mouth over a certain period is well-known. Much effort has in prior art been put into emulating the nicotine release and oral perception of a cigarette when it is smoked by a user, which means that release profiles from nicotine tablets have been thoroughly investigated in prior art. It is however an established fact that the one-to-one smoking-emulation is yet to be achieved with other means than a cigarette. Furthermore, the release of nicotine is associated with undesirable irritation in the throat, a side effect known as nicotine burning or simply burning. Consequently, a trade off between releasing sufficient amount of nicotine and avoiding undesirable nicotine burning is sought. An example of an orally disintegrating nicotine tablet is known from PCT application WO 2019/110072 A1, to Fertin Pharma A/S, related to orally disintegrating tablets with disintegration within 60 second from oral administration and suggesting the use as a sublingual tablet for positioning under the tongue, as a buccal tablet, as a tablet for melting on the tongue, or for other types of oral administering. A further example of a an orally disintegrating nicotine tablet is known from PCT application WO 2019/110075 A1, which relates to oral nicotine formulations for use in the alleviation of nicotine craving, including orally disintegrating tablets, and suggests use as a sublingual tablet for positioning under the tongue, as a buccal tablet, as a tablet for melting on the tongue, or for other types of oral administering. An example of a pouch composition is known from PCT application WO 2023/143687 A1, which relates to a pouch composition comprising e.g. at least one water insoluble fibre, at least one sugar alcohol in a total amount of 0-22 wt%, water in an amount of 12-50 wt%, nicotine and a nicotine solvent in form of a hygroscopic sweet substance capable of dissolving nicotine. An example of a pouched product is known from United Stated patent US 9 161 908 B2, which relates to a product for oral delivery of nicotine containing a core comprising a powder and a water insoluble pouch, wherein said product upon contact with purified water gives a pH of at least 6. A further example of a pouched product is known from PCT application WO 2020/157280 A1, which relates to an oral pouched tobacco-free or low tobacco nicotine product comprising a pH adjusting agent. The pH adjuster may mitigate an increase in pH in an oral pouched tobacco-free or low tobacco nicotine product upon storage. SUMMARY The invention relates to an orally disintegrating nicotine tablet for use in alleviation of nicotine craving, the tablet comprising nicotine and a pH regulating agent, wherein the tablet is administered between the lip and gum. An advantage of the invention may be that fast nicotine craving relief may be obtained while minimizing any undesirable side effects from oral nicotine administration, in particular throat irritation, also commonly referred to as throat burning or simply burning. Typically, oral nicotine release is associated with nicotine burning, an irritation of the mouth and in particular the throat. Therefore, a conventional consideration is that the release of nicotine should not be too fast in order to avoid swallowing of nicotine and thereby excessive nicotine burning. The present inventor, however, surprisingly found that nicotine burning was minimized when using an orally disintegrating nicotine tablet administered between the lip and gum. A further advantage of the invention may be that an improved nicotine effect may be obtained by using an orally disintegrating nicotine tablet administered between the lip and gum. Also, the invention provides an effective delivery of nicotine. Since the orally disintegrating nicotine tablet completely dissolves, the entire content of nicotine is released orally. Unexpectedly, the present inventors found that the tablet used in accordance with the invention led to a combination of significantly improved nicotine absorption while at the same time significantly reducing the undesirable nicotine burning side effect. Thereby, the inventive use facilitates a desirable user experience both in terms of fast and effective craving relief and in terms of a desirable mouthfeel, including decreased nicotine burning. It is noted that in the present context, the term "orally disintegrating nicotine tablet" refers to a nicotine containing orally disintegrating tablet, also referred to as a nicotine ODT, i.e. a tablet that disintegrates relative fast. It is noted that orally disintegrating tablets, or ODTs, may sometimes be referred to as fast disintegrating tablets, or FDTs. In embodiments of the invention, the orally disintegrating nicotine tablet