WO2025176912A1

WO2025176912A1 - A pouch for transmucosal delivery of an active compound

Info

Publication number: WO2025176912A1
Application number: PCT/EP2025/054918
Authority: WO
Inventors: Nicholas Rose
Original assignee: State Mode Medical Ltd
Current assignee: State Mode Medical Ltd
Priority date: 2024-02-23
Filing date: 2025-02-24
Publication date: 2025-08-28
Anticipated expiration: 2026-08-23
Also published as: GB2638465A; GB202402603D0

Abstract

A pouch for controlling release of a neuroactive and/or psychoactive compound in the mouth of a human or animal subject, the pouch comprising: a liquid permeable cover; and a plurality of dissolvable lozenges contained within the cover, each of the plurality of lozenges comprising: a matrix material forming a shape of the lozenge, said shape having a surface area, the matrix material being dissolvable in the mouth of the human or animal subject at a dissolution rate; and a neuroactive and/or psychoactive compound suspended within the matrix material at a compound concentration, wherein each lozenge has a known release rate of the neuroactive and/or psychoactive compound in the mouth of the user that is determined based on the surface area, the dissolution rate and the compound concentration and is sustained within upper and lower release rate limits over a release time period.

Description

A POUCH FOR TRANSMUCOSAL DELIVERY OF AN ACTIVE COMPOUND

Technical field

The invention relates to intraoral delivery of a brain-penetrant drug. More specifically, the invention relates to an intraoral, transmucosal delivery of a brain-penetrant neuroactive, psychoactive or bioactive substance and/or compound.

Background

Commonly, the delivery of neuroactive, psychoactive and bioactive compounds to a subject results in changes in mood, perception, cognition and/or behaviour.

There is increasing interest in the use of neuroactive compounds for medical purposes, such as treating mental health disorders. However, there are several challenges associated with the delivery of neuroactive compounds as a treatment.

One such challenge is dosing. Neuroactive, psychoactive and bioactive compounds often have a narrow therapeutic window. That is, the dose must be carefully controlled to remain in a narrow envelope over time. Determination of the dose may be based on absorption of the compound and/or a neurological effect on the subject. Tight control of dose avoids, on one hand, toxicity or, on the other hand, lack of efficacy.

Controlling the dose can be challenging, as known delivery systems produce a release of psychoactive or neuroactive compounds that varies significantly over time.

As used herein, the term ‘neuroactive compound’ encompasses substances that interact or affect the nervous system of a human or animal subject (subject hereafter). Neuroactive compounds can affect the function, communication, or regulation of neurons and neural activity. They may influence neurotransmitter release, receptor binding, or neuronal excitability. Not all neuroactive substances are necessarily psychoactive, as some may primarily affect physiological processes without causing noticeable changes in mental state. An example of a neuroactive substance is acetylcholine, which plays a vital role in nerve signal transmission.

As used herein, the term ‘psychoactive compound’ encompasses substances that can affect the brain and alter mental processes of a subject such as mood, perception, cognition, and behaviour. These substances act on the central nervous system and can induce changes in consciousness and thought patterns. Examples of psychoactive substances include drugs like LSD, psilocybin (found in magic mushrooms), MDMA, and THC (found in marijuana).

As used herein, the term ‘bioactive compound’ encompasses substances that have an effect on living organisms, encompassing both neurological and non-neurological effects. Bioactive compounds may interact with various biomolecules and biological systems, impacting physiological processes beyond just the nervous system. These effects can include antioxidant properties, anti-inflammatory actions, hormonal regulation, and more. Bioactive substances can be found in various natural sources like plants, animals, and microorganisms. Bioactive compounds may be found in Ganoderma Sichuanense (Reishi Mushroom) and Lion’s mane mushroom.

The neuroactive, psychoactive and bioactive compounds referred to herein are compounds that are capable of passing the blood-brain barrier. These compounds are therefore termed brain-penetrant compounds. Such compounds may also be termed Central Nervous System (CNS)-active or CNS-penetrant, meaning that they not only are capable of passing through the blood-brain barrier, but are also pharmacologically active in the CNS. The effect of brainpenetrant compounds is that they are able to be absorbed by the brain or wider CNS directly from blood vessels.

Summary

According to the invention in an aspect, there is provided a pouch for controlling release of a neuroactive and/or psychoactive compound in the mouth of a human or animal subject, the pouch comprising: a liquid permeable cover; and a plurality of dissolvable lozenges contained within the cover, each of the plurality of lozenges comprising: a matrix material forming a shape of the lozenge, said shape having a surface area, the matrix material being dissolvable in the mouth of the human or animal subject at a dissolution rate; and a neuroactive and/or psychoactive compound suspended within the matrix material at a compound concentration, wherein each lozenge has a known release rate of the neuroactive and/or psychoactive compound in the mouth of the user that is determined based on the surface area, the dissolution rate and the compound concentration and is sustained within upper and lower release rate limits over a release time period.

Such a pouch allows for precise control and maintenance of a release rate of the neuroactive and/or psychoactive compound over a sustained period of time. As the matrix material dissolves, the neuroactive and/or psychoactive compound is released from the lozenges at a controlled rate. By combining a plurality of lozenges in a single pouch, the combination of release rates of each lozenge can be selected to allow fine control over the overall release rate of the pouch. The invention therefore allows for a finely determined release rate of a neuroactive and/or psychoactive compound that can be within tolerances over a sustained period of time.

Optionally, a first lozenge of the plurality of lozenges has a first surface area and comprises a first matrix material and a first compound concentration of a first neuroactive and/or psychoactive compound for providing a first release rate of the first neuroactive and/or psychoactive compound, and wherein a second lozenge of the plurality of lozenges has a second surface area and comprises a second matrix material and a second compound concentration of a second neuroactive, and/or psychoactive compound for providing a second release rate.

Optionally, the first matrix material is different to the second matrix material; the first compound concentration is different to the second compound concentration; and/or the first surface area is different to the second surface area.

Optionally, the first release rate is different to the second release rate. A release rate of the pouch may be based on a combination of the first and second release rates and/or a permeability of the liquid permeable cover.

Optionally, the overall release rate of the pouch is determined based, at least in part, on a combination of a plurality of neuroactive and/or psychoactive compounds in the first and/or second lozenges.

Optionally, the active compound of at least one of the plurality of lozenges is substantially evenly distributed within the matrix material.

Optionally, one or more of the plurality of lozenges includes an absorption enhancer for increasing a rate of absorption of the neuroactive and/or psychoactive compound by the human or animal subject.

Optionally, one or more of the plurality of lozenges includes an absorption inhibitor for reducing a rate of absorption of the neuroactive and/or psychoactive compound by the human or animal subject. Optionally, at least one of the plurality of lozenges comprises an oral indicator configured to be released into the mouth of the human or animal subject after a predetermined time period.

Optionally, the oral indicator is suspended within the matrix material of the at least one of the plurality of lozenges, and wherein the predetermined period of time is dependent on the dissolution rate of the matrix material and/or a surface area of the lozenge.

Optionally, the oral indicator comprises a substance configured to change a flavour profile in the mouth of the human or animal subject.

Optionally, the first and/or second matrix materials include a sugar-based substance, a cellulose derivative substance and/or a polymer.

Optionally, the release time period is one of: in a range from 5 minutes to 3 hours; in a range from 5 minutes to 2 hours; in a range from 5 minutes to 1 hour; and in a range from 30 seconds to 30 minutes.

Optionally, the pouch further comprises an inner pouch, the inner pouch comprising: an inner liquid permeable cover; and a plurality of further dissolvable lozenges contained within the inner cover

Optionally, a liquid permeability of the permeable cover is different to a liquid permeability of the inner permeable cover.

Optionally, the one or more lozenges of the plurality of lozenges comprises a plurality of layers, wherein an outer layer comprises an outer matrix material and an outer compound concentration, and wherein an inner layer comprises an inner matrix material and an inner compound concentration.

Optionally, the inner layer is exposed upon at least partial dissolution of the outer layer.

Optionally, a release rates of the neuroactive and/or psychoactive compound caused by the outer layer and the inner are within the upper and lower release rate limits.

Optionally, the neuroactive and/or psychoactive compound comprises psilocybin or psilocyn. According to the invention in an aspect, there is provided a pouch for transmucosal delivery of a neuroactive, psychoactive and/or bioactive compound in the mouth of a human or animal subject. The pouch comprises a liquid permeable cover; and a plurality of dissolvable lozenges contained within the cover. Each of the plurality of lozenges comprises a matrix material; and a neuroactive, psychoactive and/or bioactive compound suspended within the matrix material. A first lozenge of the plurality of lozenges comprises a first matrix material and a first concentration of a neuroactive, psychoactive and/or bioactive compound suspended in the first matrix for delivering a first dosage profile to the human or animal subject. A second lozenge of the plurality of lozenges comprises a second matrix material and a second concentration of the and/or a further neuroactive, psychoactive and/or bioactive compound suspended in the second matrix for delivering a second dosage profile to the human or animal subject.

In an example, the first lozenge and second lozenge comprise the same neuroactive, psychoactive and/or bioactive compound.

In an example, the first lozenge and second lozenge comprise the same matrix material.

In an example, the concentration of the or each neuroactive, psychoactive and/or bioactive compound suspended in each respective matrix material is the same.

In an example, the first lozenge and second lozenge are the same.

In an example, the first and the second dosage profiles combine to determine an overall dosage profile for the pouch.

In an example, the overall dosage profile is determined based, at least in part, on a combination of a plurality of neuroactive, psychoactive and/or bioactive compounds in the first and/or second lozenges.

In an example, the first and/or the second dosage profiles result in an absorption rate and/or a release rate of the neuroactive, psychoactive and/or bioactive compound that remains within a range defined by an upper dosage profile threshold and a lower dosage profile threshold.

In an example, the first and/or second dosage profile is dependent on one or more of: a surface area of the first and/or second lozenge; a concentration of the first and/or the further neuroactive, psychoactive and/or bioactive compound suspended in the first and/or the second matrix; and a rate of dissolution of the first and/or second matrix. In an example, the first concentration and/or the second concentration is substantially evenly distributed within the first and/or second matrix material.

In an example, the first concentration is less than the second concentration.

In an example, the first and/or second lozenges include an absorption enhancer for increasing a rate of absorption of the neuroactive, psychoactive and/or bioactive compound by the human or animal subject.

In an example, the first and/or second lozenges include an absorption inhibiter for reducing a rate of absorption of the neuroactive, psychoactive and/or bioactive compound by the human or animal subject.

In an example, at least one of the plurality of lozenges comprises an oral indicator configured to be released into the mouth of the human or animal subject after a predetermined time period.

In an example, the oral indicator comprises a substance configured to change a flavour profile in the mouth of the human or animal subject.

In an example, the first and/or second matrix materials include a sugar-based substance, a cellulose derivative substance and/or a polymer.

In an example, the pouch further comprises an inner pouch and the inner pouch comprises an inner liquid permeable cover; and a plurality of inner dissolvable lozenges contained within the inner cover. Each of the plurality of inner lozenges comprises an inner matrix material; and the and/or a further neuroactive, psychoactive and/or bioactive compound suspended within the inner matrix material.

In an example, a first inner lozenge of the plurality of inner lozenges comprises a first inner matrix material and a first inner concentration of the and/or a further neuroactive, psychoactive and/or bioactive compound suspended in the first inner matrix; and a second inner lozenge of the plurality of inner lozenges comprises a second inner matrix material and a second inner concentration of the and/or a further neuroactive, psychoactive and/or bioactive compound suspended in the second inner matrix. In an example, a liquid permeability of the permeable cover is different to a liquid permeability of the inner permeable cover.

In an example, the first lozenge of the plurality of lozenges comprises a plurality of layers, wherein a first layer of the plurality of layers comprises the first matrix material and the first concentration of the neuroactive, psychoactive and/or bioactive compound suspended in the first matrix for delivering the first dosage profile to the human or animal subject; and a second layer of the plurality of layers comprises a third matrix material and a third concentration of the and/or a further neuroactive, psychoactive and/or bioactive compound suspended in the third matrix for delivering a third dosage profile to the human or animal subject.

In an example, the second layer is exposed upon at least partial dissolution of the first layer.

In an example, a difference between an absorption rate and/or a release rate of the neuroactive or bioactive compound in the first and second dosage profiles is less than a dosage threshold value.

In an example, the neuroactive, psychoactive and/or bioactive compound comprises psilocybin or psilocyn.

Brief descri tion of the drawings

Embodiments of the disclosed methods and apparatus will be described in detail below, with reference to the accompanying drawings, in which:

Figure 1 is an example of a typical dosage profile for an active compound that is ingested orally by a user;

Figure 2 is a section through an example pouch for transmucosal delivery of an active compound;

Figure 3 is an example of a pouch that comprises an outer liquid permeable cover and an inner liquid permeable cover; and

Figure 4 is an example of a section through a lozenge for inclusion in a pouch.

Detailed Description

Generally, disclosed herein are drug delivery systems configured for transmucosal delivery of a brain-penetrant neuroactive, psychoactive and/or bioactive substance or compound (active compound from hereon). In exemplary arrangements, a pouch includes a liquid permeable outer cover that contains a plurality of lozenges. Each lozenge may comprise at least one active compound that is suspended in a matrix material. The matrix material is a solid and forms the shape of the lozenge. The matrix is configured to dissolve in the mouth of a subject over a period of time for controlled release of the active compound for transmucosal delivery of the active compound. Each lozenge has a predetermined release rate of the active compound. An overall release rate of the pouch is proportional to an aggregate of the release rates of the plurality of lozenges. The permeability of the liquid permeable outer cover also controls the pouch release rate.

Accordingly, the overall release rate of the pouch may be determined by combining within the pouch a plurality of lozenges having various release rate. This allows the overall release rate of a pouch to be finely controlled and sustained within upper and lower release rate limits over a prolonged time period.

Known methods of delivery of active compounds include tablets, capsules and edibles that are ingested for delivery of the drug orally through the stomach. Figure 1 shows a typical dosage profile 100 that can be seen using these methods of delivery. The y-axis of Figure 1 shows absorption of the active compound, and the x-axis shows time. Because the active compound is delivered in a single dose, levels of compound absorption grow to a peak and then reduce over time, as shown in the typical dosage profile 100.

The typical dosage profile 100 can mean that significant amounts of time are spent with the subject in the region 102 where compound absorption is too high, and which results in excessive neurological effects and impairment of the subject, or in the region 104 where compound absorption is too low, and which results in insufficient neurological effect to achieve a desired outcome for the subject.

The inventors have appreciated that it is desirable to maintain active compound absorption in a more stable state. The invention achieves this by suspending the active compound in a matrix material that forms a lozenge. In exemplary arrangements the matrix material may form a lozenge having the appearance of a pastille, a gummy or a boiled sweet (or hard candy). The matrix material dissolves over time in the mouth of the user and this releases the active compound that is suspended in the matrix material at a controlled release rate. As shown in Fig.1 , a controlled release rate of the active compound allows a clinician (or other professional) to control the compound absorption rate so it may be maintained in a third, or optimal, region 106, which results in a desired outcome for the subject without having excessive neurological effect and the resulting impairment. It is noted that the optimal region is dependent on the requirements of the clinical situation and its determination is not part of the methods and apparatus disclosed herein.

The optimal dosage profile 108 increases active compound absorption until it reaches the optimal region 106, where it flattens off to maintain the correct level of active compound absorption over time. Active compound absorption may remain within predetermined compound absorption limits, such as the limits of the optimal region 106. The optimal region 106 is in a range from an upper dosage profile threshold 110 to a lower dosage profile threshold 112. Figure 1 shows the optimal dosage profile 108 as being flat after reaching the optimal region 106. However, it will be appreciated that the optimal dosage profile 108 may exhibit increased or decreased active compound absorption over time, whilst staying within the optimal region 106.

In order to achieve a dosage profile that remains in the region 106, a sustained and controlled release of the active compound is provided by the methods and apparatus disclosed herein.

The term ‘dosage profile’ as used herein encompasses a rate of active compound absorption by a subject. The active compound absorption and rate of active compound release may be proportional but not necessarily equal. Differences in active compound absorption and rate of active compound release may be based on factors that are specific to a human or animal subject. Accordingly, the optimal region 106 of Figure 1 may be expressed as a region having a rate of active compound absorption, or rate of release of the active compound from the lozenge as it dissolves, that lies between upper and lower thresholds 110, 112. Methods and apparatus disclosed herein are related to controlling a rate of release of an active compound.

The term “lozenge” as used herein may encompass any type or shape of tablet configured to dissolve in the mouth of a subject at a known rate. Accordingly, the lozenge may be hard or brittle, gum like structure or have any other structure capable of holding its own weight. The lozenge is formed by the matrix material and is configured to be held in the mouth of a user and dissolved over time to release the active compound held therein.

Figure 2 shows a section through a pouch 200 for transmucosal delivery of an active compound. The pouch includes a liquid permeable cover 202. Contained within the cover 202 are a plurality of lozenges 204, 206, 208. One or more of the lozenges 204, 206, 208 includes a matrix material that is dissolvable in the mouth of a human or animal subject. The matrix material forms the shape of the one or more lozenges 204, 206, 208. In exemplary arrangements, the matrix material forms at least an outer layer of the one or more lozenges 204, 206, 208. In some arrangements one opr more matrix materials may the entire shape of the lozenge. An active compound is suspended in the matrix such that it is released into the mouth of the human or animal subject as the matrix dissolves. The matrix material is dissolvable over time for controlled release of the active compound. In exemplary arrangements, the rate of dissolution of the matrix material may be configured to dissolve in water at a rate of 15g-30g per 100g of water at a temperature of 20 degrees Celsius. In a specific example, the matrix material may dissolve in water at a rate of 24g per 100g of water at a temperature of 20 degrees Celsius.

A first lozenge 204 includes a first matrix material and has a first compound concentration of at least one active compound suspended within the first matrix. The first matrix material forms the outer shape of the first lozenge 204, giving the first lozenge a first surface area. The first lozenge 204 is configured to release the active compound(s) at a first release rate, which is defined by a combination of the dissolution rate of the first matrix material, the first compound concentration and the first surface area. The first release rate may proportional to a first dosage profile associated with the first lozenge 204.

A second lozenge 206 includes a second matrix material and has a second compound concentration of at least one active compound suspended within the second matrix. The second matrix material forms the outer shape of the second lozenge 204, giving the second lozenge a second surface area. The second lozenge 206 is configured to release the active compound(s) at a second release rate, which is defined by a combination of the second matrix material, the second compound concentration and the second surface area. The second release rate may define a second dosage profile associated with the second lozenge 206.

In exemplary arrangements, the first release rate is different to the second release rate. The pouch 200 includes a plurality of lozenges two or more of which may have different release rates, although it is noted that some of the plurality of lozenges may have the same release rate.

As mentioned above, the release rate of a lozenges may be dependent on one or more of: a rate of dissolution of the matrix material; a concentration of the at least one active compound; and a surface area of the lozenge that is exposed in the mouth of the human or animal subject (this may be proportional to the size of the lozenge). Accordingly, a lozenge may be configured using the features identified in the paragraph above to have a specific release rate profile. If the surface area of a lozenge is increased then the rate of release of the active compound is increased, and vice-versa. If the rate of dissolution of the matrix material is increased then the rate of release of the active compound is increased, and vice-versa. If the concentration of the active compound suspended in the matrix material is increased then the rate of release of the active compound is increased, and vice-versa.

The liquid permeable cover 202 is configured to allow saliva to pass through for dissolution of the lozenges 204, 206, 208. The permeability of the liquid permeable cover 202 may determine the overall compound release rate of the pouch 200. A more permeable cover will increase the release rate of the pouch and vice-versa.

One or more of the lozenges 204, 206, 208 may be configured to give an oral indication to the human or animal subject after a period of time. An oral indication encompasses any indication that may be detected by the subject through the mouth. For example, the oral indication may include a flavour that is detectable by the subject, or a chemical reaction in the mouth of the subject.

In one specific example, one or more lozenges 204, 206, 208 may include a flavoured compound suspended in a matrix material thereof. The flavoured compound may be suspended in the matrix material below a surface of the lozenge 204, 206, 208 such that an outer layer of the lozenge 204, 206, 208 must be dissolved before the flavoured compound is released into the mouth of the subject. The time taken to dissolve the outer layer of the lozenge 204, 206, 208 is dependent on a rate of dissolution of the matrix material of the outer layer and/or a surface area of the outer layer. In other arrangements, the flavoured compound may be replaced with an alternative compound giving an alternative oral indication to the subject.

The oral indication may be timed to coincide with a particular point in the overall dosage profile (or active compound release) of the pouch 200. For example, the oral indication may prompt the subject to remove the pouch 200 from their mouth when a required amount of the active compound has been released or a required dosage has been reached. The oral indication may illicit an involuntary action in the subject, such as a foul taste that causes the subject to instantly and rapidly remove the pouch 200 from the mouth. The release rate of the active compound from the pouch 200 is based on (and may be proportional to) the combined release rates of the plurality of lozenges 204, 206, 208 in the pouch. This gives fine control over the release rate of the pouch 200 over time. Specifically, a desired release rate of the pouch may be achieved by combining, within the pouch a plurality of lozenges 204. 206, 208 that each has a known release rate. The controlled release of the lozenges 204, 206, 208 means that the pouch release rate will remain within upper and lower release rate limits over a period of time. The period of time may be the length of time that it takes for one or more of the lozenges to dissolve, or for a layer of one or more of the lozenges to dissolve. The period of time may be in a range from in a range from 5 minutes to 3 hours; in a range from 5 minutes to 2 hours; in a range from 5 minutes to 1 hour; and in a range from 30 seconds to 30 minutes. Release of the total active compound suspended in the matrix material is not instant, but is controlled over time.

Figure 3 shows an exemplary pouch 300 including an outer liquid permeable cover 302 and an inner liquid permeable cover 304.

The outer liquid permeable cover includes a plurality of outer lozenges 306. The inner liquid permeable cover 304 is at least partially contained within the outer liquid permeable cover 302. The inner liquid permeable cover 304 includes one or more inner lozenges 308.

The outer liquid permeable cover 302 and the inner liquid permeable cover 304 may have different permeabilities. For example, the inner liquid permeable cover 304 may have a greater permeability than the outer liquid permeable cover 302. Alternatively, the inner liquid permeable cover 304 may have a lower permeability than the outer liquid permeable cover 302. The relative permeability of the inner and outer liquid permeable covers 302, 304 may allow greater control over the release rate of the active compound and the overall release rate profile of the pouch 300.

For example, it may be possible to have: simultaneous or overlapping release of the active compound from the outer lozenges 306 and the inner lozenges 308; or sequential release of the active compound from the outer lozenges 306 and the inner lozenges 308. In addition, the release rate of the inner lozenges 308 may be restricted or enhanced by greater or lesser permeability of the inner liquid permeable cover 304.

Figure 4 shows a section through a lozenge 400 for inclusion in pouch 200, 300. In the example of Figure 4, the lozenge 400 has a circular section and may be spherical or disc shaped. It will be appreciated that any other shapes of lozenge are possible and are encompassed by this disclosure, e.g., a rhomboid, a capsule shape or a pill shape.

The exemplary lozenge 400 includes a plurality of layers and, in the case of Figure 4, a first layer 402 and a second layer 404. It will be apparent to a skilled person that further layers may be included, if desired or that there may be a single layer.

Each of the plurality of layers 402, 404 of the lozenge 400 includes a matrix material and at least one active compound suspended in the matrix. The matrix material may be configured to be dissolvable in the mouth of a subject. The active compound is suspended in the matrix so that it may be released in the mouth of the subject as the matrix material dissolves and absorbed transmucosally. Accordingly, the rate of release of the active compound may be controlled by the concentration of the active compound suspended in the matrix and/or the rate of dissolution of the matrix material in the mouth of the subject.

In exemplary arrangements, the plurality of layers 402, 404 may be concentric and share a common centre. The first layer 402 may encompass the second layer 404. Where further layers are included, these may also be concentric and be encompassed by one or more outer layers.

The first layer 402 may be adjacent to the second layer 404. In other arrangements, a spacer layer containing no active compound may be placed between the first and second layers 402, 404. The spacer layer may be dissolvable and may comprise the matrix material.

The thickness of each layer 402, 404 may be substantially uniform. Further, the thickness of each layer 402, 404 may be less than a layer thickness threshold value. As will be apparent from the description below, this allows release of the active compound to remain within upper and lower release rate limits as the surface area of the layer that is exposed in the mouth of the subject reduces with dissolution, thereby affecting the release rate of the active compound.

The matrix material may comprise a sugar-based material, e.g., sucrose, glucose or fructose. These sugars have a pleasant taste, are readily available and are relatively inexpensive. In some exemplary arrangements, the matrix material may comprise cellulose derivatives, such as hydroxypropyl methylcellulose (HPMC), which can form gels when hydrated and can provide sustained release of the active compound. Polymers such as polyvinyl alcohol (PVA) and polyethylene glycol (PEG) could also be used as a matrix material, and can provide enhanced drug solubility, increased stability, and controlled release. In addition, flavourings, colours, and sweeteners can be added to the matrix material to improve the palatability of the lozenge. For example, fruit flavours, such as strawberry or orange, are commonly used, as well as sweeteners such as stevia and xylitol, which can provide a sweet taste without increasing the caloric content of the lozenge.

The matrix material may be configured to dissolve at a known rate in the mouth of the subject, which permits consistent and sustained release of the active compound as the matrix material dissolves.

The active compound may be any neuroactive, psychoactive or bioactive substance or compound, e.g., psilocybin or psilocylin. In exemplary arrangements, the active compound may be evenly distributed within the first and/or second layers 402, 404. The concentration of the active compound within the first and/or second layers 402, 404 may be isotropic.

As discussed in greater detail below, one or more of a concentration of the active compound, the dissolution rate of the matrix material, a layer thickness and a combination of active compounds in one or more layers may be used to control a release rate profile associated with each layer 402, 404 and an overall release rate profile associated with the lozenge 400.

In exemplary arrangements, the fist layer 402 comprises a outer matrix material and an outer concentration of the active compound suspended in the outer matrix material. The outer matrix material and the outer concentration of the active compound are configured to achieve an outer release rate profile for the active compound.

In some examples the first release rate profile may provide compound absorption and/or a compound release rate that remains within release rate limits over a given time period (see Fig. 1).

The inner layer 404 may comprise an inner matrix material and an inner concentration of the active compound suspended in the inner matrix material. The inner matrix material and the inner concentration of the active compound are configured to achieve an inner release rate profile for the active compound.

The inner release rate profile may provide compound absorption and/or a compound release that remains within further release rate boundaries over a further given time period. Further, the inner release rate profile may be substantially the same as the outer release rate profile. An active compound absorption rate and/or an active compound release rate of the outer dosage profile may differ from an active compound absorption rate and/or an active compound release rate of the inner dosage profile by less than a dosage threshold value.

The outer matrix material may be the same as the inner matrix material.

The concentration of the active compound in the outer layer 402 may be less than the concentration of the active compound in the inner layer 404. In particular, if the matrix material of the outer layer 402 and the inner layer 404 are the same or otherwise have the same dissolution rate, the concentration of the active compound in the outer layer 402 may be less than the concentration of the active compound in the inner layer 404. By increasing the concentration of the active compound in the second layer 404, the release rate of the lozenge may be maintained whilst the size of the lozenge decreases due to dissolution.

In some arrangements, if the matrix material of the outer layer 402 dissolves more quickly than the matrix material of the inner layer 404 then the concentration of the active compound in the outer layer 402 may be the same or greater than the concentration of the active compound in the inner layer 404.

Determination of the concentration of the active compound and/or the rate of dissolution of the matrix material in the outer and inner layers 402, 404 may be based on the desired outer and inner release rate profiles. Further, the determination of the concentration of the active compound and/or the rate of dissolution of the matrix material in the outer and inner layers 402, 404 may be based on one or more of a thickness of the outer and/or inner layers 402, 404; and a surface area of the outer and/or inner layers 402, 404 that is exposed in the mouth of the subject.

The concentration of the active compound in the outer and inner layers 402, 404 and/or the rate of dissolution of the matrix material in the outer and inner layers 402, 404 determines the rate of release of the active compound and therefore the release rate profile of the lozenge 400 as it dissolves. The concentration of the active compound in each layer and/or the rate of dissolution of the matrix material in each layer may be chosen based on layer thickness.

The thickness of the outer layer 402 may be determined such that the rate of release and/or the rate of absorption of the active compound results in a dosage profile that remains within the release rate limits at the beginning of the dissolution of the outer layer 402 and at the end of the dissolution of the outer layer 402, based on the rate of release of the active compound. Further, the inner and outer surface areas 406, 408 of the outer layer 402 are determined in combination with the rate of release of the active compound to achieve the desired release rate profile.

A plurality of active compounds may be included in the outer layer and suspended within the matrix material. The ratio between the plurality of active compounds may affect the release rate profile. For example, if the outer layer includes a combination of psilocybin and psilocyn then the rate of absorption by the subject will be affected. Psilocyn is more quickly absorbed by the subject and so a higher ratio of psilocyn compared to psilocybin will increase the rate of absorption.

The above also applies to the inner layer 404.

In one specific example, the matrix material in the inner layer 404 and/or outer layer 402 may comprise (or consist of) Isomalt. A concentration of active compound suspended in the matrix material may be in a range from 5mg-15mg of active compound per 5mg-10mg of matrix material. In a specific example, the concentration may be approximately 10mg of active compound per 5mg-10mg of matrix material. It will be appreciated that the concentration will depend on the user, the active compound(s) used and the desired outcomes for the user. The lozenge 400 may include an outer protective coating of Shellac or Carnauba Wax.

One or more of the plurality of lozenges in a pouch may be spherical and have a diameter in a range from 0.5mm to 4mm, or in a range from 1mm to 4mm. One or more of the plurality of lozenges in a pouch may have shapes other than spheres. A volume of one or more of the lozenges may be in a range from 0.06 mm³ to 34mm³. A surface area of one or more of the plurality of lozenges in a pouch may be in a range from 0.75mm² to 55mm².

One or more of the plurality of lozenges in a pouch may comprise an outer coating. The outer coating may be dissolvable in the mouth of the subject. A thickness of the outer layer may be configured to time a release of the active compound contained in the matrix material. Accordingly, a first lozenge may have an outer coating having a first thickness, and a second lozenge may have an outer coating of a second thickness that is greater than the first thickness. The first thickness may be zero in that the first lozenge may have no outer coating.

In addition to the active compound, one or more of the plurality of layers 402, 404 of the lozenge 400 may include absorption enhancer. For example, the outer and/or inner layers may include a substance that increases the permeability of the oral mucosa of the subject to allow for greater absorption. Alternatively, or in addition, one or more of the plurality of layers 402, 404 may include an absorption inhibiter. Where absorption enhancers and/or inhibitors are used in one or more layers 402, 404, the concentration of the active compound and the rate of dissolution of the matrix material in the associated layers may be altered based on the effect of the absorption enhancer and/or absorption inhibiter.

In exemplary arrangements, one or more spacer or boundary layers may be incorporated into the lozenge 400. The spacer layers may include a substance configured to provide a certain pH value within the mouth of the subject. For example, the spacer layer may include sodium bicarbonate, nitric acid, citric acid and/or other compounds in order to maintain a specific pH level in the mouth. The pH level in the mouth can affect the absorption of the active compound.

It is noted that the optimal region may be different for different subjects as each subject may react to the active compound differently. Accordingly, it is envisaged that a number of lozenges may be available, wherein the dissolution rate and/or the active compound concentration in each layer of each lozenge is configured to provide a dosage profile that remains within different dosage threshold boundaries.

In arrangements, a plurality of lozenges may be manufactured, each having one of a plurality of predetermined release rate profiles. A pouch may be manufactured by selecting two or more of the plurality of lozenges such that their release rate profiles combine to create a desired overall dosage profile. The overall dosage profile may be determined based on physiological characteristics of a human or animal subject to whom the active compound is to be delivered.

It will be apparent to those skilled in the art that various modifications and variations can be made to the disclosed systems and methods. Other embodiments will be apparent to those skilled in the art from consideration of the specification and practice of the disclosed systems and methods. It is intended that the specification and examples be considered as exemplary only, with a true scope being indicated by the following claims and their equivalents.

Claims

1. A pouch for controlling release of a neuroactive and/or psychoactive compound in the mouth of a human or animal subject, the pouch comprising: a liquid permeable cover; and a plurality of dissolvable lozenges contained within the cover, each of the plurality of lozenges comprising: a matrix material forming a shape of the lozenge, said shape having a surface area, the matrix material being dissolvable in the mouth of the human or animal subject at a dissolution rate; and a neuroactive and/or psychoactive compound suspended within the matrix material at a compound concentration, wherein each lozenge has a known release rate of the neuroactive and/or psychoactive compound in the mouth of the user that is determined based on the surface area, the dissolution rate and the compound concentration and is sustained within upper and lower release rate limits over a release time period.

2. The pouch according to claim 1 , wherein a first lozenge of the plurality of lozenges has a first surface area and comprises a first matrix material and a first compound concentration of a first neuroactive and/or psychoactive compound for providing a first release rate of the first neuroactive and/or psychoactive compound, and wherein a second lozenge of the plurality of lozenges has a second surface area and comprises a second matrix material and a second compound concentration of a second neuroactive, and/or psychoactive compound for providing a second release rate.

3. The pouch according to claim 2, wherein: the first matrix material is different to the second matrix material; the first compound concentration is different to the second compound concentration; and/or the first surface area is different to the second surface area.

4. The pouch according to claim 2 or 3, wherein the first and the second release rates combine to determine an overall release rate for the pouch.

5. The pouch according to claim 4, wherein the overall release rate of the pouch is determined based, at least in part, on a combination of a plurality of neuroactive and/or psychoactive compounds in the first and/or second lozenges.

6. The pouch according to any preceding claim, wherein the active compound of at least one of the plurality of lozenges is substantially evenly distributed within the matrix material.

7. The pouch according to any preceding claim, wherein one or more of the plurality of lozenges includes an absorption enhancer for increasing a rate of absorption of the neuroactive and/or psychoactive compound by the human or animal subject.

8. The pouch according to any preceding claim, wherein one or more of the plurality of lozenges includes an absorption inhibitor for reducing a rate of absorption of the neuroactive and/or psychoactive compound by the human or animal subject.

9. The pouch according to any preceding claim, wherein at least one of the plurality of lozenges comprises an oral indicator configured to be released into the mouth of the human or animal subject after a predetermined time period.

10. The pouch according to claim 9, wherein the oral indicator is suspended within the matrix material of the at least one of the plurality of lozenges, and wherein the predetermined period of time is dependent on the dissolution rate of the matrix material and/or a surface area of the lozenge.

11. The pouch according to claim 9 or 10, wherein the oral indicator comprises a substance configured to change a flavour profile in the mouth of the human or animal subject.

12. The pouch according to any preceding claim, wherein the first and/or second matrix materials include a sugar-based substance, a cellulose derivative substance and/or a polymer.

13. The pouch according to any preceding claim, wherein the release time period is one of: in a range from 5 minutes to 3 hours; in a range from 5 minutes to 2 hours; in a range from 5 minutes to 1 hour; and in a range from 30 seconds to 30 minutes.

14. The pouch according to any preceding claim, further comprising an inner pouch, the inner pouch comprising: an inner liquid permeable cover; and a plurality of further dissolvable lozenges contained within the inner cover

15. The pouch according to claim 14, wherein a liquid permeability of the permeable cover is different to a liquid permeability of the inner permeable cover.

16. The pouch according to any preceding claim, wherein the one or more lozenges of the plurality of lozenges comprises a plurality of layers, wherein an outer layer comprises an outer matrix material and an outer compound concentration, and wherein an inner layer comprises an inner matrix material and an inner compound concentration.

17. The pouch according to claim 16, wherein the inner layer is exposed upon at least partial dissolution of the outer layer.

18. The pouch according to claim 16 or 17, wherein a release rates of the neuroactive and/or psychoactive compound caused by the outer layer and the inner are within the upper and lower release rate limits.

19. The pouch according to any preceding claim wherein the neuroactive and/or psychoactive compound comprises psilocybin or psilocyn.