EP-4734952-A1 - ORAL TABLET WITH IMPROVED UNIFORMITY OF CONTENT OF ACTIVES

Abstract

The invention relates an oral tablet suitable for active pharmaceutical ingredients comprising an intragranular portion and an extragranular portion. The intragranular portion comprising a plurality of granules each comprising one or more active pharmaceutical ingredients; one or more binders; and one or more excipients comprising one or more sweeteners in an amount of at least 20% by weight of the plurality of granules. The extragranular portion comprising a population of particles comprising non-directly compressible (non-DC) sweetener particles, the non-DC sweetener particles having not been granulated prior to tableting and providing the oral tablet with a plurality of discrete non-DC areas evenly distributed in the oral tablet or at least one module of the oral tablet.

Inventors

• NIELSEN, BRUNO PROVSTGAARD
• MARTINUSSEN, Helle

Assignees

• Fertin Pharma A/S

Dates

Publication Date

20260506

Application Date

20230629

Claims (20)

1. 1. An oral tablet suitable for active pharmaceutical ingredients comprising an intragranular portion and an extragranular portion, the intragranular portion comprising a plurality of granules each comprising: one or more active pharmaceutical ingredients; one or more binders; and one or more excipients comprising one or more sweeteners in an amount of at least 20% by weight of the plurality of granules, the extragranular portion comprising a population of particles comprising: non-directly compressible (non-DC) sweetener particles, the non-DC sweetener particles having not been granulated prior to tableting and providing the oral tablet with a plurality of discrete non-DC areas evenly distributed in the oral tablet or at least one module of the oral tablet.
2. 2. The oral tablet according to claim 1, wherein the oral tablet is a chewable tablet.
3. 3. The oral tablet according to any one of claims 1 or 2, wherein the extragranular portion constitutes at least 20% by weight of the oral tablet.
4. 4. The oral tablet according to any one of the preceding claims, wherein the extragranular portion constitutes at least 40% by weight of the oral tablet.
5. 5. The oral tablet according to any one of the preceding claims, wherein the intragranular portion constitutes at least 30% by weight of the oral tablet.
6. 6. The oral tablet according to any one of the preceding claims, wherein the intragranular portion constitutes at least 50% by weight of the oral tablet.
7. 7. The oral tablet according to any one of the preceding claims, wherein the plurality of discrete non-DC areas of the extragranular portion provide increased saliva generation upon mastication of the oral tablet.
8. 8. The oral tablet according to any one of the preceding claims, wherein saliva generation upon mastication of the oral tablet is increased compared to an oral tablet where the discrete areas of the extragranular portion are based on DC sweetener particles.
9. 9. The oral tablet according to any one of the preceding claims, wherein the non-DC sweetener particles of the extragranular portion is present in an amount of at least 10% by weight of the oral tablet.
10. 10. The oral tablet according to any one of the preceding claims, wherein the non-DC sweetener particles of the extragranular portion is present in an amount of at least 30% by weight of the extragranular portion.
11. 11. The oral tablet according to any one of the preceding claims, wherein the non-DC sweetener particles of the extragranular portion comprise one or more non-DC sugar alcohol particles.
12. 12. The oral tablet according to any one of the preceding claims, wherein the non-DC sweetener particles of the extragranular portion are selected from the group consisting of non-DC particles of erythritol, maltitol, xylitol, isomalt, lactitol, mannitol, and combinations thereof.
13. 13. The oral tablet according to any one of the preceding claims, wherein the non-DC sweetener particles of the extragranular portion are selected from the group consisting of non-DC particles of erythritol, maltitol, xylitol, isomalt, and combinations thereof.
14. 14. The oral tablet according to any one of the preceding claims, wherein the non-DC sweetener particles of the extragranular portion are selected from the group consisting of non-DC particles of erythritol, maltitol, xylitol, and combinations thereof.
15. 15. The oral tablet according to any one of the preceding claims, wherein the non-DC sweetener particles of the extragranular portion comprise one or more non-DC saccharide particles.
16. 16. The oral tablet according to any one of the preceding claims, wherein the non-DC sweetener particles of the extragranular portion are selected from the group consisting of non-DC particles of dextrose, saccharose, fructose, and combinations thereof.
17. 17. The oral tablet according to any one of the preceding claims, wherein the non-DC sweetener particles of the extragranular portion comprise non-DC dextrose particles.
18. 18. The oral tablet according to any one of the preceding claims, wherein the non-DC sweetener particles of the extragranular portion comprise non-DC fructose particles.
19. 19. The oral tablet according to any one of the preceding claims, wherein the non-DC sweetener particles having not been granulated prior to tableting and providing the oral tablet with a plurality of discrete non-DC areas are evenly distributed in the oral tablet among the plurality of granules of the intragranular portion.
20. 20. The oral tablet according to any one of the preceding claims, wherein the extragranular portion further comprises directly compressible (DC) sweetener particles.

Description

ORAL TABLET WITH IMPROVED UNIFORMITY OF CONTENT OF ACTIVES FIELD OF THE INVENTION The present invention relates to the field of oral tablets comprising distant portions of tablet material suitable for delivery of active pharmaceutical ingredients. In particular, the invention relates to tablets having an intragranular portion serving to improve content uniformity of one or more active pharmaceutical ingredients together with an extragranular portion serving to improve saliva generation. BACKGROUND OF THE INVENTION Various attempts have been made in the past with an aim to improve content uniformity of active pharmaceutical ingredients in tablets in order to secure accurate dosing for patients in need thereof. Accurate dosing may be important for certain actives in order to avoid overdosing with potentially lethal consequences and also to provide precise vehicles for administration of actives. Uniformity of content is of particular importance for active pharmaceutical ingredients where lack of safety and appropriate delivery may become fatal in alleviating or treating medical conditions. Mainly relevant for tablets intended for delivery of actives in the gastrointestinal tract, focus has traditionally been on formulating encapsulations for targeted delivery of the actives in the gastrointestinal tract. Suitable solutions for administration of active pharmaceutical ingredients with high efficacy in tablets for delivery in the oral cavity has been particularly challenging since such actives are usually to be provided in low doses. In parallel, oral tablets have been provided in the past with special focus on providing increased saliva generation and thereby promoting release of active ingredients from the oral tablets to the oral cavity. These tablets have mainly been intended for delivery and uptake of actives through the oral mucosa upon release of the actives in the oral cavity. While improved saliva generation may be obtained by these tablets and fast release of the actives may be accommodated, certain challenges may arise with respect to accurate dosing of certain actives due to increased saliva production. Uncontrolled delivery of actives may inherently be increased as a consequence of too much deviation from the targeted content of the actives in such tablets, e.g., a less beneficial content uniformity of the actives. Combining means for an improved content uniformity of actives, such as low dosis actives, with increased saliva generation may be particularly desired but has hitherto been difficult to obtain due to the intrinsic opposite function of these systems. Traditionally, means for improved content uniformity, such as encapsulations, may not be compatible with a desire to have increased saliva generation and thereby improved delivery of actives in the oral cavity. This may for example be the case where the means for an improved content uniformity prevents delivery to the oral mucosa upon increased saliva generation. Also, this may be the case where the means for obtaining an improved content uniformity prevents increased saliva generation, even if means as present for increased saliva generation. Particularly, it may be a challenge to formulate saliva promoting oral tablets with active pharmaceutical ingredients in low doses which may be required for actives where the efficacy is high and would otherwise cause problems if provided in a higher dose. In that case, the oral tablet means for improved content uniformity of the actives may be compromised by the formulation of the saliva promoting means in the oral tablets. This may be the case, where the means for saliva promotion is based on a combination of non-directly compressible (non-DC) and directly compressible (DC) sweetener particles and the means for improved content uniformity is based on means that may counteract saliva promotion. Oral tablets have traditionally been preferred for administration of active pharmaceutical ingredients both in terms of convenience and compliance. Oral tablets have certain benefits compared to other delivery vehicles for oral administration of active ingredients. Typically, such oral tablets are made by direct compression or compaction methods where a powder tablet material and an active ingredient are pressed into defined tablets with appropriate strength to provide a pharmacological effect to a patient in need thereof in medical formulations or to provide a health benefit for consumers in nutraceutical formulations. In terms of low dose active pharmaceutical ingredients, and even high dose active pharmaceutical ingredients, one option is to apply such actives in an oral tablet made by direct compression without special means for providing a high content uniformity of the actives. However, due to the process of tablet manufacturing, a challenge of powder segregation may apply. This may result in a less beneficial content uniformity in the oral tablet made by the process. And this may also cause issues in te