EP-4739287-A1 - DISSOLVABLE ORALLY ADHERING NICOTINE TABLET

Abstract

A dissolvable orally adhering nicotine tablet for sustained delivery of nicotine is disclosed, the tablet is a multilayer tablet comprising a first layer and a second layer, wherein the first layer is a mucoadhesive layer comprising a mucoadhesive, and wherein the second layer comprises at least one sugar alcohol and nicotine.

Inventors

• WITTORFF, HELLE
• NIELSEN, BRUNO PROVSTGAARD
• MARTINUSSEN, Helle

Assignees

• Fertin Pharma A/S

Dates

Publication Date

20260513

Application Date

20240708

Claims (20)

1. 1. A dissolvable orally adhering nicotine tablet for sustained delivery of nicotine, wherein the tablet is a multilayer tablet comprising a first layer and a second layer, wherein the first layer is a mucoadhesive layer comprising a mucoadhesive, and wherein the second layer comprises at least one sugar alcohol and nicotine.
2. 2. The tablet according to claim 1, wherein the first layer comprises at least one sugar alcohol.
3. 3. The tablet according to claim 1 or 2, wherein the tablet is a compressed tablet.
4. 4. The tablet according to any of claims 1-3, wherein the tablet is composed of a plurality of compressed particles.
5. 5. The tablet according to any of claims 1-4, wherein the first and the second layers are fused by compression.
6. 6. The tablet according to any of claims 1-5, wherein the mucoadhesive comprises a mucoadhesive selected from the group consisting of xanthan gum, konjac gum, tara gum, gellan gum, locust bean gum, gum arabic, alginic acid, alginate, pullulan, tragacanth gum, gum karaya, fenugreek gum, cassia gum, carrageenan, agar, pectin, hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), hydroxy ethylcellulose, ethylcellulose (EC), carboxymethyl cellulose (CMC) and salts thereof, dextran, guar gum, polyvinyl pyrrolidone (PVP), gelatin, casein, acrylic acid polymers (carbomers), acrylic acid esters, acrylic acid copolymers, and any combination thereof.
7. 7. The tablet according to any of claims 1-6, wherein the mucoadhesive comprises an ionic mucoadhesive.
8. 8. The tablet according to any of claims 1-7, wherein the mucoadhesive comprises a mucoadhesive selected from the group consisting of xanthan gum, gellan gum, gum arabic, alginic acid, alginate, carrageenan, agar, and any combination thereof.
9. 9. The tablet according to any of claims 1-8, wherein the mucoadhesive comprises xanthan gum and/or gum arabic.
10. 10. The tablet according to any of claims 1-9, wherein the mucoadhesive comprises gum arabic.
11. 11. The tablet according to any of claims 1-10, wherein the mucoadhesive comprises xanthan gum.
12. 12. The tablet according to any of claims 1-11, wherein the mucoadhesive comprises a cellulose derivative.
13. 13. The tablet according to any of claims 1-12, wherein the mucoadhesive comprises a cellulose derivative selected from the group consisting of hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), hydroxy ethylcellulose, ethylcellulose (EC), carboxymethyl cellulose (CMC), and salts thereof, and any combination thereof.
14. 14. The tablet according to any of claims 1-13, wherein the first layer comprises a cellulose derivative mucoadhesive in an amount of at least 20% by weight of the first layer.
15. 15. The tablet according to any of claims 1-14, wherein the first layer comprises at least two different types of mucoadhesives.
16. 16. The tablet according to any of claims 1-15, wherein the mucoadhesive of the first layer comprises at least one natural gum and at least one cellulose derivative.
17. 17. The tablet according to any of claims 1-16, wherein the mucoadhesive of the first layer comprises gum arabic and at least one cellulose derivative.
18. 18. The tablet according to any of claims 1-17, wherein the first layer comprises the mucoadhesive in an amount of at least 35% by weight of the first layer, such as at least 40% by weight of the first layer, such as at least 50% by weight of the first layer, such as at least 55% by weight of the first layer, such as at least 60% by weight of the first layer.
19. 19. The tablet according to any of claims 1-18, wherein the first layer comprises the mucoadhesive in an amount of no more than 90% by weight of the first layer, such as no more than 85% by weight of the first layer, such as no more than 80% by weight of the first layer.
20. 20. The tablet according to any of claims 1-19, wherein the second layer is free of mucoadhesive.

Description

DISSOLVABLE ORALLY ADHERING NICOTINE TABLET FIELD OF INVENTION The invention relates to a dissolvable orally adhering nicotine tablet for sustained release according to the claims. BACKGROUND Several oral tablets are known to provide sustained release of nicotine. However, such tablets may be inconvenient for the user due to the slow dissolution of the tablets. Additionally, slow dissolution may result in an unintended swallowing of nicotine, which further would result in an unpleasant experience for the user. Besides being an unpleasant experience, unintended swallowing would prohibit buccal release of nicotine. Thus, a lowered efficacy and undesired side effects such as off- taste, throat irritation and/or hiccups may be expected. At the same time, due to the slow dissolution, providing tablets with a good mouthfeel is desirable, as users may otherwise discourage from use, or may eject the tablets prematurely due to discomfort. It is an object of the present invention to overcome the disadvantages of the prior art. SUMMARY The invention relates to a dissolvable orally adhering nicotine tablet for sustained delivery of nicotine, wherein the tablet is a multilayer tablet comprising a first layer and a second layer, wherein the first layer is a mucoadhesive layer comprising a mucoadhesive, and wherein the second layer comprises at least one sugar alcohol and nicotine. An advantage of the invention may be that a desirable sustained delivery of nicotine may be obtained. An advantage of the present invention may be that a localized release of nicotine may be obtained. Due to the mucoadhesive layer, the tablet may be immobilized in the intended position between the gum and the lip, while the second layer facilitates adherence towards one side only, thus preventing unpleasant adherence between the gum and lip. It is noted that the tablet preferably is inserted to adhere to the mucosal surface of the gum. Furthermore, due to the effective adherence facilitated by the mucoadhesive layer, a convenient, pleasurable user experience is provided. First of all, a more discreet nicotine delivery format is provided compared to other common nicotine delivery formats such as chewing gum, lozenges and pouch. Not only since unintended appearance of the tablet from its gum-lip position may be prevented, but also since the tablet size may be reduced. Typically, smaller tablets positioned between the gum and the lip may easily dislocate from their intended position and may thus be unintentionally chewed or swallowed or even fall out of the mouth. Such unintended dislocation may also result in excessive nicotine and buffer irritation in the mouth and throat due to faster than intended release of nicotine and/or buffer followed by swallowing. In turn, this also leads to inefficient utilization of nicotine. Adhering tablets may, however, also be perceived as unpleasant, as the user may often perceive the tablet as holding the gum and the lip together due to the adhesive nature of the tablet. The present invention provides a discreet tablet, which may be smaller than typical tablets for intraoral use and thus avoid any unpleasant bulky sensation. At the same time, the tablet may be firmly adhered to the gum or lip to avoid unintentional dislocation of the tablet, yet avoid the disadvantages typically associated with adherent tablets, due to the multilayer design comprising a second layer with sugar alcohol and nicotine and less adhesive properties. These advantages may be obtained without requiring any subsequent user action, such as special use, removal of residual product etc. A further advantage of the invention may be that a sustained release of nicotine may be obtained in a simple manner. Specifically, by including a mucoadhesive selectively in the first layer, the tablet may after insertion between the gum and the lip adhere to the mucosal surface of the gum or to the lip, preferably to the gum, whereby the tablet is immobilized. This immobilization facilitates sustained release of nicotine, as the tablet is inserted into a low exposure region of the oral cavity with low saliva flux and minimum interaction with the tongue. Thereby the disintegration time of the tablet may be significantly prolonged. On the other hand, the adhesion either to the mucosal surface of the gum or to the lip facilitates a significant improvement in the user experience, as simultaneous adhesion to the mucosal surface of the gum and the lip is perceived as unpleasant, e.g. since it prevents the gum and the lip from moving freely relative to each other. Based on this insight, the tablet comprises both a first layer being a mucoadhesive layer and a second layer comprising sugar alcohol and nicotine. It is noted that the intended use of the tablet is insertion between the gum and the lip, with the first layer facing the gum or the lip, preferably the gum, whereby the first layer adheres to the gum or lip to facilitate immobilization of the tablet. Thus