Substrates for delivering biologically active agents

Abstract

1. A substrate (12) for delivering a biologically active agent, comprising: a crosslinked silicone matrix formed by crosslinking a silicone polymer using at least one crosslinking agent comprising a tetraalkoxysilane, the crosslinked silicone matrix defining a plurality of domains; and a composition contained within the domains of the crosslinked silicone matrix, the composition comprising at least one monomeric glycol and at least one biologically active agent.

Description

[Technical field]

[0001] The present invention relates to substrates for delivering biologically active agents, aerosol-generating articles comprising the substrates, transdermal patches comprising the substrates, oral delivery products comprising the substrates, and methods of making the substrates. [Background technology]

[0002] It is known to use silicone polymers to form substrates for delivering bioactive agents. For example, silicone polymers have been used in implantable systems and topical applications to deliver bioactive agents.

[0003] Silicone polymers may be used to form a silicone matrix with a bioactive agent releasably contained therein. Because release of the bioactive agent from the silicone matrix can affect delivery of the bioactive agent to the user, controlled release of the bioactive agent from the silicone matrix is ​​desirable.

[0004] Previously, it has been proposed to control the release of bioactive substances from silicone matrices by incorporating additives into the silicone matrix.For example, additives may be included in the silicone matrix to provide a domain in which bioactive substances can be releasably included.However, including additives may be undesirable.For example, certain additives may not have the biocompatibility suitable for inclusion in a substrate to deliver bioactive substances to a user.Inclusion of certain additives may also undesirably increase manufacturing costs.

[0005] Forming a matrix from a silicone polymer can involve vulcanization of the silicone polymer, which can require long cure times, thereby preventing efficient manufacturing of substrates that include silicone polymers.

[0006] It would be desirable to provide improved substrates for delivering bioactive agents, particularly those that can provide a controlled release profile of the bioactive agent and that can be efficiently manufactured. Summary of the Invention

[0007] The present invention relates to a substrate for delivering a biologically active agent. The substrate may comprise a crosslinked silicone matrix. The crosslinked silicone matrix may be formed by crosslinking a silicone polymer using at least one crosslinking agent. The at least one crosslinking agent may comprise a tetraalkoxysilane. The crosslinked silicone matrix may define a plurality of domains. The substrate may comprise a composition. The composition may be contained within the domains of the crosslinked silicone matrix. The composition may comprise at least one monomeric glycol. The composition may comprise at least one biologically active agent.

[0008] In accordance with the present invention, there is provided a substrate for delivering a biologically active agent, the substrate comprising a crosslinked silicone matrix formed by crosslinking a silicone polymer using at least one crosslinking agent comprising a tetraalkoxysilane, the crosslinked silicone matrix defining a plurality of domains, and a composition contained within the domains of the crosslinked silicone matrix, the composition comprising at least one monomeric glycol and at least one biologically active agent.

[0009] The present invention also relates to an aerosol-generating article comprising a substrate for delivering a biologically active agent. The substrate may comprise a crosslinked silicone matrix. The crosslinked silicone matrix may be formed by crosslinking a silicone polymer using at least one crosslinking agent. The at least one crosslinking agent may comprise a tetraalkoxysilane. The crosslinked silicone matrix may define a plurality of domains. The substrate may comprise a composition. The composition may be contained within the domains of the crosslinked silicone matrix. The composition may comprise at least one monomeric glycol. The composition may comprise at least one biologically active agent.

[0010] In accordance with the present invention, there is provided an aerosol-generating article comprising a substrate for delivering a biologically active agent, the substrate comprising a crosslinked silicone matrix formed by crosslinking a silicone polymer using at least one crosslinking agent comprising a tetraalkoxysilane, the crosslinked silicone matrix defining a plurality of domains, and a composition contained within the domains of the crosslinked silicone matrix, the composition comprising at least one monomeric glycol and at least one biologically active agent.

[0011] The present invention also relates to a transdermal patch comprising a substrate for delivering a biologically active agent. The substrate may comprise a crosslinked silicone matrix. The crosslinked silicone matrix may be formed by crosslinking a silicone polymer using at least one crosslinking agent. The at least one crosslinking agent may comprise a tetraalkoxysilane. The crosslinked silicone matrix may define a plurality of domains. The substrate may comprise a composition. The composition may be contained within the domains of the crosslinked silicone matrix. The composition may comprise at least one monomeric glycol. The composition may comprise at least one biologically active agent.

[0012] In accordance with the present invention, there is provided a transdermal patch for delivering a biologically active agent, the substrate comprising a crosslinked silicone matrix formed by crosslinking a silicone polymer using at least one crosslinking agent comprising a tetraalkoxysilane, the crosslinked silicone matrix defining a plurality of domains, and a composition contained within the domains of the crosslinked silicone matrix, the composition comprising at least one monomeric glycol and at least one biologically active agent.

[0013] The present invention also relates to an oral delivery product comprising a substrate for delivering a biologically active agent. The substrate may comprise a crosslinked silicone matrix. The crosslinked silicone matrix may be formed by crosslinking a silicone polymer using at least one crosslinking agent. The at least one crosslinking agent may comprise a tetraalkoxysilane. The crosslinked silicone matrix may define a plurality of domains. The substrate may comprise a composition. The composition may be contained within the domains of the crosslinked silicone matrix. The composition may comprise at least one monomeric glycol. The composition may comprise at least one biologically active agent.

[0014] In accordance with the present invention, there is provided an oral delivery product comprising a substrate for delivering a biologically active agent, the substrate comprising a crosslinked silicone matrix formed by crosslinking a silicone polymer using at least one crosslinking agent comprising a tetraalkoxysilane, the crosslinked silicone matrix defining a plurality of domains, and a composition contained within the domains of the crosslinked silicone matrix, the composition comprising at least one monomeric glycol and at least one biologically active agent.

[0015] The present invention also relates to a method of making a substrate for delivering a biologically active agent. The method may include mixing a silicone polymer, at least one monomeric glycol, at least one biologically active agent, and at least one crosslinking agent to form a mixture. The at least one crosslinking agent may include a tetraalkoxysilane. The method may include curing the mixture to form the substrate.

[0016] In accordance with the present invention, there is provided a method of producing a substrate for delivering a biologically active agent, the method comprising mixing a silicone polymer, at least one monomeric glycol, at least one biologically active agent, and at least one crosslinker comprising a tetraalkoxysilane to form a mixture, and curing the mixture to form the substrate.

[0017] In the following description, references to features or characteristics of a substrate for delivering a biologically active substance according to the present invention also apply to substrates of aerosol-generating articles according to the present invention, substrates of transdermal patches according to the present invention, substrates of oral delivery products according to the present invention, and methods for manufacturing substrates according to the present invention, unless otherwise stated.

[0018] Providing a substrate comprising at least one monomeric glycol formed by crosslinking a silicone polymer comprising a tetraalkoxysilane and a crosslinked silicone matrix can advantageously facilitate controlled release of at least one biologically active agent from the substrate.

[0019] Providing a substrate comprising at least one monomeric glycol and a crosslinked silicone matrix formed by crosslinking a silicone polymer using at least one crosslinking agent comprising a tetraalkoxysilane can advantageously facilitate efficient manufacture of the substrate. In particular, it has been surprisingly found that providing a substrate comprising at least one monomeric glycol and a crosslinked silicone matrix formed by crosslinking a silicone polymer using at least one crosslinking agent comprising a tetraalkoxysilane can advantageously reduce the cure time required for vulcanization of the silicone polymer.

[0020] As used herein in connection with the present invention, the term "aerosol-generating article" is used to describe an article that includes a substrate that is heated to generate and deliver an inhalable aerosol to a user.

[0021] Substrates comprising at least one monomeric glycol and a crosslinked silicone matrix formed by crosslinking a silicone polymer using at least one crosslinker comprising a tetraalkoxysilane may advantageously be thermally stable at temperatures reached by the substrate during use of an aerosol-generating article comprising the substrate.

[0022] The substrate comprising at least one monomeric glycol and a crosslinked silicone matrix formed by crosslinking a silicone polymer using at least one crosslinker comprising a tetraalkoxysilane may exhibit desirable mechanical properties for a transdermal patch comprising the substrate or an oral delivery product comprising the substrate. In particular, the elasticity of the substrate may be such that the oral delivery product comprising the substrate provides a desired oral sensory experience to the user during use.

[0023] The substrate comprising at least one monomeric glycol and a crosslinked silicone matrix formed by crosslinking a silicone polymer using at least one crosslinker comprising a tetraalkoxysilane can be advantageously molded into shapes and sizes suitable for oral delivery products comprising the substrate.

[0024] As used herein in connection with the present invention, the term "crosslinked silicone matrix" is used to describe a three-dimensional network formed by crosslinking silicone polymers.

[0025] As used herein in connection with the present invention, the term "domain" is used to describe pores within a crosslinked silicone matrix. A composition may be contained within the domains of the crosslinked silicone matrix.

[0026] Unless otherwise stated, the weight percentages of the components of the substrates listed herein are based on the total weight of the substrate.

[0027] The weight percent of a component can be calculated by dividing the total weight of the components used to form the substrate by the total weight of the substrate and multiplying by 100.

[0028] The substrate may be formed by crosslinking any suitable silicone polymer.

[0029] Preferably, the silicone polymer comprises a linear silicone polymer.

[0030] Preferably, the silicone polymer comprises a hydroxyl-terminated silicone polymer.

[0031] Preferably, the silicone polymer comprises a linear hydroxyl-terminated silicone polymer.

[0032] Suitable hydroxyl-terminated silicone polymers include, but are not limited to, hydroxyl-terminated polydialkylsiloxanes, such as hydroxyl-terminated polydimethylsiloxane (PDMS-OH) and hydroxyl-terminated polydiethylsiloxane, and hydroxyl-terminated polydiphenylsiloxane.

[0033] Preferably, the silicone polymer comprises hydroxyl-terminated polydimethylsiloxane.

[0034] The molecular weight of the silicone polymer can be selected based on the desired mechanical properties of the substrate. For example, the molecular weight of the silicone polymer can be selected to achieve the desired flexibility of the substrate. This can be particularly advantageous for transdermal patches, including the substrate or oral delivery products that include the substrate.

[0035] The silicone polymer may have a molecular weight of at least about 25,000 grams / mole, or at least about 30,000 grams / mole, or at least about 35,000 grams / mole.

[0036] The silicone polymer can have a molecular weight of up to about 60,000 grams / mole, or up to about 55,000 grams / mole, or up to about 50,000 grams / mole.

[0037] The silicone polymer can have a molecular weight of about 25,000 grams / mole to about 60,000 grams / mole, or about 25,000 grams / mole to about 55,000 grams / mole, or about 25,000 grams / mole to about 50,000 grams / mole.

[0038] The silicone polymer can have a molecular weight of about 30,000 grams / mole to about 60,000 grams / mole, or about 30,000 grams / mole to about 55,000 grams / mole, or about 30,000 grams / mole to about 50,000 grams / mole.

[0039] The silicone polymer can have a molecular weight of about 35,000 grams / mole to about 60,000 grams / mole, or about 35,000 grams / mole to about 55,000 grams / mole, or about 35,000 grams / mole to about 50,000 grams / mole.

[0040] The silicone polymer may be used in an amount of at least about 35 weight percent, or at least about 40 weight percent, or at least about 45 weight percent to form a crosslinked silicone matrix.

[0041] The silicone polymer may be used in an amount up to about 85 weight percent, or up to about 80 weight percent, or up to about 75 weight percent to form a crosslinked silicone matrix.

[0042] The silicone polymer may be used in an amount of about 35 weight percent to about 85 weight percent, or about 35 weight percent to about 80 weight percent, or about 35 weight percent to about 75 weight percent to form a crosslinked silicone matrix.

[0043] The silicone polymer may be used in an amount of about 40 weight percent to about 85 weight percent, or about 40 weight percent to about 80 weight percent, or about 40 weight percent to about 75 weight percent to form a crosslinked silicone matrix.

[0044] The silicone polymer may be used in an amount of about 45 weight percent to about 85 weight percent, or about 45 weight percent to about 80 weight percent, or about 45 weight percent to about 75 weight percent.

[0045] The silicone polymer may be crosslinked using at least one crosslinker selected from the group consisting of tetraethyl orthosilicate (TEOS), silicon glycerate (Si-GLY), and silicon 1,2-propylene glycolate (Si-PGL).

[0046] As used herein in connection with the present invention, "tetraethyl orthosilicate" and "TEOS" refer to a compound having the following chemical structure: [ka]

[0047] As used herein in connection with the present invention, "silicon glycerate" and "Si-GLY" refer to a compound having the following chemical structure: [ka]

[0048] As used herein in connection with the present invention, "1,2-silicone propylene glycolate" and "Si-PGL" refer to a compound having the following chemical structure: [ka]

[0049] Preferably, the at least one crosslinking agent comprises one or both of silicon glycerate and silicon 1,2-propylene glycolate, i.e., preferably, the at least one crosslinking agent comprises silicon glycerate, or silicon 1,2-propylene glycolate, or both silicon glycerate and silicon 1,2-propylene glycolate.

[0050] Crosslinking the silicone polymer using at least one crosslinking agent including one or both of silicon glycerate and silicon 1,2-propylene glycolate can advantageously substantially increase the vulcanization rate of the silicone polymer, which can advantageously facilitate efficient manufacturing of the substrate.

[0051] In certain embodiments, it is preferred that the at least one crosslinking agent comprises 1,2-propylene glycolic acid silicon.

[0052] When the at least one cross-linking agent comprises silicon glycerate, the silicon glycerate may be used in a solution that includes glycerol.

[0053] When silicon glycerate is used in a solution containing glycerol, the solution may have a molar ratio of silicon glycerate to glycerol of about 1:0.5 to about 1:2.9.

[0054] When the at least one crosslinker comprises silicon 1,2-propylene glycolate, the silicon 1,2-propylene glycolate may be used in a 1,2-propylene glycol solution.

[0055] When silicon 1,2-propylene glycolate is used in a solution containing 1,2-propylene glycol, the solution may have a molar ratio of silicon 1,2-propylene glycolate to 1,2-propylene glycol of about 1:0.5 to about 1:2.9.

[0056] The use of at least one crosslinking agent in the solution containing at least one monomeric glycol to form the substrate can affect the cure time required to vulcanize the silicone polymer.

[0057] The amount of crosslinking agent used to crosslink the silicone polymer can be selected based on the desired degree of vulcanization of the silicone polymer. A high degree of vulcanization of the silicone polymer can advantageously enhance the mechanical properties of the substrate.

[0058] An excess of crosslinking agent may be used to crosslink the silicone polymer.

[0059] Excess crosslinking agent may undergo hydrolysis to produce silicon dioxide during the manufacture of the substrate. The use of excess crosslinking agent to crosslink the silicone polymer may advantageously strengthen the crosslinked silicone matrix, which may enhance the mechanical properties of the substrate.

[0060] Using an excess of crosslinking agent to crosslink the silicone polymer can advantageously improve the reaction rate, which can increase the vulcanization rate of the silicone polymer.

[0061] The molar ratio of the at least one crosslinker to the silicone polymer can be at least about 1:2, or at least about 1:1, or at least about 2:1.

[0062] The molar ratio of the at least one crosslinker to the silicone polymer can be up to about 45:1, or up to about 40:1, or up to about 35:1.

[0063] The molar ratio of the at least one crosslinker to the silicone polymer can be from about 1:2 to about 45:1, or from about 1:2 to about 40:1, or from about 1:2 to about 35:1.

[0064] The molar ratio of the at least one crosslinker to the silicone polymer can be from about 1:1 to about 45:1, or from about 1:1 to about 40:1, or from about 1:1 to about 35:1.

[0065] The molar ratio of the at least one crosslinker to the silicone polymer can be from about 2:1 to about 45:1, or from about 2:1 to about 40:1, or from about 2:1 to about 35:1.

[0066] When the at least one crosslinker comprises TEOS, the molar ratio of TEOS to silicone polymer can be at least about 5:1.

[0067] When the at least one crosslinker comprises TEOS, the molar ratio of TEOS to silicone polymer can be up to about 35:1.

[0068] When the at least one crosslinker comprises TEOS, the molar ratio of TEOS to silicone polymer can be from about 5:1 to about 35:1.

[0069] When the at least one crosslinker comprises silicon glycerate, the molar ratio of silicon glycerate to silicone polymer can be at least about 5:1.

[0070] When the at least one crosslinker comprises silicon glycerate, the molar ratio of silicon glycerate to silicone polymer can be up to about 20:1.

[0071] When the at least one crosslinker comprises silicon glycerate, the molar ratio of silicon glycerate to silicone polymer can be from about 5:1 to about 20:1.

[0072] When the at least one crosslinker comprises silicon 1,2-propylene glycolate, the molar ratio of silicon 1,2-propylene glycolate to silicone polymer can be at least about 2:1.

[0073] When the at least one crosslinker comprises silicon 1,2-propylene glycolate, the molar ratio of silicon 1,2-propylene glycolate to silicone polymer can be up to about 5:1.

[0074] When the at least one crosslinker comprises silicone 1,2-propylene glycolate, the molar ratio of silicone 1,2-propylene glycolate to silicone polymer can be from about 2:1 to about 5:1.

[0075] At least one crosslinking agent may be used in an amount of at least about 0.5 weight percent, or at least about 0.75 weight percent, or at least about 1 weight percent.

[0076] The at least one crosslinking agent may be used in an amount up to about 18 weight percent, or up to about 15 weight percent, or up to about 12 weight percent.

[0077] The at least one crosslinking agent may be used in an amount of from about 0.5 weight percent to about 18 weight percent, or from about 0.5 weight percent to about 15 weight percent, or from about 0.5 weight percent to about 12 weight percent.

[0078] The at least one crosslinking agent can be used in an amount of from about 0.75 weight percent to about 18 weight percent, or from about 0.75 weight percent to about 15 weight percent, or from about 0.75 weight percent to about 12 weight percent.

[0079] The at least one crosslinking agent can be used in an amount of from about 1 weight percent to about 18 weight percent, or from about 1 weight percent to about 15 weight percent, or from about 1 weight percent to about 12 weight percent.

[0080] The substrate comprises a composition contained within domains of a crosslinked silicone matrix. The composition comprises at least one monomeric glycol.

[0081] The inclusion of at least one monomeric glycol may advantageously provide uniformly dispersed domains within the crosslinked silicone matrix, which may advantageously result in the at least one biologically active agent being uniformly dispersed within the crosslinked silicone matrix, which may advantageously aid in achieving a controlled release profile of the at least one biologically active agent from the substrate.

[0082] The inclusion of at least one monomeric glycol can provide hydrophilic domains within the crosslinked silicone matrix, which can advantageously facilitate the manufacture of substrates according to the present invention that include hydrophilic bioactive materials.

[0083] The inclusion of at least one monomeric glycol may advantageously avoid the need to include undesirable additives in the substrate. For example, the inclusion of at least one monomeric glycol may avoid the need to include polyethylene oxide (PEO) in the substrate. The inclusion of at least one monomeric glycol may avoid the need to include fatty acids, such as linoleic acid and oleic acid, in the substrate.

[0084] The inclusion of at least one monomeric glycol can advantageously allow for cost-effective and efficient manufacture of a substrate for delivering a bioactive agent that provides a controlled release profile for the bioactive agent.

[0085] The at least one monomeric glycol can be selected based on the desired properties of the domains of the crosslinked silicone matrix.

[0086] The at least one monomeric glycol can be selected based on the desired release profile of the at least one biologically active agent.

[0087] The monomeric glycols may contain up to seven carbon atoms.

[0088] The monomeric glycols may contain at least two carbon atoms. For example, the monomeric glycols may contain from two carbon atoms to seven carbon atoms, or from two carbon atoms to six carbon atoms, or from two carbon atoms to five carbon atoms, or from two carbon atoms to four carbon atoms, or from two carbon atoms to three carbon atoms.

[0089] The monomeric glycols may contain at least three carbon atoms. For example, the monomeric glycols may contain from three carbon atoms to seven carbon atoms, or from three carbon atoms to six carbon atoms, or from three carbon atoms to five carbon atoms, or from three carbon atoms to four carbon atoms.

[0090] Preferably the monomeric glycol contains three carbon atoms.

[0091] Suitable monomeric glycols include, but are not limited to, glycerol and 1,2-propylene glycol. The at least one monomeric glycol may include one or both of glycerol and 1,2-propylene glycol.

[0092] The at least one monomeric glycol may include glycerol.

[0093] The at least one monomeric glycol may include 1,2-propylene glycol.

[0094] The at least one monomeric glycol may include both glycerol and 1,2-propylene glycol.

[0095] In aerosol-generating articles that include a substrate, glycerol and 1,2-propylene glycol can transport other compounds, such as biologically active agents, that are released from the substrate upon heating.

[0096] At least one monomeric glycol in the composition may be derived from a single source.

[0097] At least one monomeric glycol in the composition may be derived from multiple sources.

[0098] The at least one monomeric glycol may be added during the manufacture of the substrate, separate from the other components used to form the substrate.

[0099] The at least one monomeric glycol may be added during the manufacture of the substrate in combination with other components used to form the substrate. For example, the at least one monomeric glycol may be added during the manufacture of the substrate in combination with the at least one crosslinking agent. For example, the at least one crosslinking agent may be used in a solution that includes the at least one monomeric glycol.

[0100] At least one monomeric glycol may be formed during the manufacture of the substrate. For example, if the at least one crosslinker comprises silicon glycerate, glycerol may be formed during vulcanization of the silicone polymer. If the at least one crosslinker comprises silicon 1,2-propylene glycolate, 1,2-propylene glycol may be formed during vulcanization of the silicone polymer.

[0101] The substrate may include at least one monomeric glycol in an amount of at least about 10 weight percent, or at least about 15 weight percent, or at least about 20 weight percent.

[0102] The substrate may include at least one monomeric glycol in an amount up to about 60 weight percent, or up to about 55 weight percent, or up to about 50 weight percent.

[0103] The substrate may include at least one monomeric glycol in an amount from about 10 weight percent to about 60 weight percent, or from about 10 weight percent to about 55 weight percent, or from about 10 weight percent to about 50 weight percent.

[0104] The substrate may include at least one monomeric glycol in an amount from about 15 weight percent to about 60 weight percent, or from about 15 weight percent to about 55 weight percent, or from about 15 weight percent to about 50 weight percent.

[0105] The substrate may include at least one monomeric glycol in an amount from about 20 weight percent to about 60 weight percent, or from about 20 weight percent to about 55 weight percent, or from about 20 weight percent to about 50 weight percent.

[0106] The weight percent of the at least one monomeric glycol is calculated by dividing the total weight of the at least one monomeric glycol present in the substrate by the total weight of the substrate and multiplying by 100. The total weight of the at least one monomeric glycol present in the substrate is calculated by summing the following: the weight of any monomeric glycol that is added during the manufacture of the substrate separately from other components used to form the substrate, the weight of any monomeric glycol that is added during the manufacture of the substrate in combination with other components used to form the substrate, such as at least one crosslinking agent; and the weight of any monomeric glycol that is formed during the manufacture of the substrate.

[0107] When the substrate contains both glycerol and 1,2-propylene glycol, the substrate may contain about the same amount of glycerol by weight as 1,2-propylene glycol. When the substrate contains both glycerol and 1,2-propylene glycol, the substrate preferably contains more glycerol by weight than 1,2-propylene glycol.

[0108] When the substrate includes both glycerol and 1,2-propylene glycol, the substrate may include glycerol and 1,2-propylene glycol in a ratio of at least about 1:1 by weight, or at least about 1.5:1 by weight, or at least about 2:1 by weight.

[0109] When the substrate includes both glycerol and 1,2-propylene glycol, the substrate may include glycerol and 1,2-propylene glycol in a ratio of up to about 59:1 by weight, or up to about 40:1 by weight, or up to about 25:1 by weight.

[0110] When the substrate includes both glycerol and 1,2-propylene glycol, the substrate may include glycerol and 1,2-propylene glycol in a ratio of about 1:1 to about 59:1 by weight, or about 1:1 to about 40:1 by weight, or about 1:1 to about 25:1 by weight.

[0111] When the substrate includes both glycerol and 1,2-propylene glycol, the substrate may include glycerol and 1,2-propylene glycol in a ratio of about 1.5:1 to about 59:1 by weight, or about 1.5:1 to about 40:1 by weight, or about 1.5:1 to about 25:1 by weight.

[0112] When the substrate includes both glycerol and 1,2-propylene glycol, the substrate may include glycerol and 1,2-propylene glycol in a ratio of about 2:1 to about 59:1 by weight, or about 2:1 to about 40:1 by weight, or about 2:1 to about 25:1 by weight.

[0113] The inclusion of more glycerol by weight than 1,2-propylene glycol may aid in the formation of a homogeneous mixture during the manufacture of the substrate, which may advantageously result in a more uniform dispersion of the composition within the crosslinked silicone matrix, which may also advantageously facilitate the manufacture of the substrate.

[0114] The substrate may comprise polyethylene oxide.

[0115] Preferably, the substrate comprises polyethylene oxide in an amount less than about 1 weight percent, or less than about 0.5 weight percent, or less than about 0.1 weight percent.

[0116] More preferably, the substrate does not contain polyethylene oxide.

[0117] The substrate may include fatty acids such as linoleic acid and oleic acid.

[0118] Preferably, the substrate comprises fatty acids in an amount less than about 1 weight percent, or less than about 0.5 weight percent, or less than about 0.1 weight percent.

[0119] More preferably, the substrate is fatty acid free.

[0120] Preferably the substrate is free of linoleic acid.

[0121] Preferably the substrate is free of oleic acid.

[0122] The crosslinked silicone matrix may be formed by crosslinking the silicone polymer in the presence of a curing catalyst.

[0123] The cure catalyst may be selected based on the desired cure rate of the silicone polymer.

[0124] The curing catalyst may include a room temperature vulcanization catalyst.

[0125] The curing catalyst may include at least one of an aminopropyl-terminated silicone polymer, an amine, and a metal-based catalyst. Suitable aminopropyl-terminated silicone polymers include, but are not limited to, aminopropyl-terminated polydimethylsiloxane (PDMS-NH2). Suitable amines include, but are not limited to, monoamines, such as monoethanolamine, and diamines, such as 1,6-hexamethylenediamine. Suitable metal-based catalysts include, but are not limited to, dibutyltin dilaurate and stannous octoate.

[0126] The curing catalyst preferably comprises aminopropyl-terminated silicone polymer, such as aminopropyl-terminated polydimethylsiloxane.Aminopropyl-terminated silicone polymer may be biocompatible and therefore may be suitable for inclusion in substrate to deliver bioactive substances.The use of the curing catalyst comprising aminopropyl-terminated silicone polymer can thereby simplify the manufacture of substrate and improve the manufacturing efficiency of substrate.

[0127] The aminopropyl-terminated silicone polymer may have a molecular weight of at least about 400 grams / mole, or at least about 600 grams / mole, or at least about 800 grams / mole.

[0128] The aminopropyl-terminated silicone polymer can have a molecular weight of up to about 3000 grams / mole, or up to about 2800 grams / mole, or up to about 2600 grams / mole.

[0129] The aminopropyl-terminated silicone polymer can have a molecular weight of from about 400 grams / mole to about 3000 grams / mole, or from about 400 grams / mole to about 2800 grams / mole, or from about 400 grams / mole to about 2600 grams / mole.

[0130] The aminopropyl-terminated silicone polymer can have a molecular weight of from about 600 grams / mole to about 3000 grams / mole, or from about 600 grams / mole to about 2800 grams / mole, or from about 600 grams / mole to about 2600 grams / mole.

[0131] The aminopropyl-terminated silicone polymer can have a molecular weight of from about 800 grams / mole to about 3000 grams / mole, or from about 800 grams / mole to about 2800 grams / mole, or from about 800 grams / mole to about 2600 grams / mole.

[0132] The substrate may include a curing catalyst.

[0133] The substrate may include the cure catalyst in an amount of at least about 0.2 weight percent, or at least about 0.5 weight percent, or at least about 0.8 weight percent.

[0134] The substrate may include the cure catalyst in an amount up to about 12 weight percent, or up to about 10 weight percent, or up to about 8 weight percent.

[0135] The substrate may include the curing catalyst in an amount of from about 0.2 weight percent to about 12 weight percent, or from about 0.2 weight percent to about 10 weight percent, or from about 0.2 weight percent to about 8 weight percent.

[0136] The substrate may include the curing catalyst in an amount of from about 0.5 weight percent to about 12 weight percent, or from about 0.5 weight percent to about 10 weight percent, or from about 0.5 weight percent to about 8 weight percent.

[0137] The substrate may include the curing catalyst in an amount of from about 0.8 weight percent to about 12 weight percent, or from about 0.8 weight percent to about 10 weight percent, or from about 0.8 weight percent to about 8 weight percent.

[0138] The cure catalyst can be present during the formation of the crosslinked silicone matrix in an amount of at least about 0.2 weight percent, or at least about 0.5 weight percent, or at least about 0.8 weight percent.

[0139] The cure catalyst may be present in an amount up to about 12 weight percent, or up to about 10 weight percent, or up to about 8 weight percent during formation of the crosslinked silicone matrix.

[0140] The curing catalyst can be present in an amount of from about 0.2 weight percent to about 12 weight percent, or from about 0.2 weight percent to about 10 weight percent, or from about 0.2 weight percent to about 8 weight percent during formation of the crosslinked silicone matrix.

[0141] The curing catalyst can be present in an amount of from about 0.5 weight percent to about 12 weight percent, or from about 0.5 weight percent to about 10 weight percent, or from about 0.5 weight percent to about 8 weight percent during formation of the crosslinked silicone matrix.

[0142] The curing catalyst can be present in an amount of from about 0.8 weight percent to about 12 weight percent, or from about 0.8 weight percent to about 10 weight percent, or from about 0.8 weight percent to about 8 weight percent during formation of the crosslinked silicone matrix.

[0143] The substrate may include any suitable bioactive material.

[0144] The bioactive agent may be a hydrophilic bioactive agent.

[0145] Suitable bioactive agents include, but are not limited to, alkaloids, cannabinoids, furazolidone, ganglofen hydrochloride, and diclofenac sodium.

[0146] Suitable cannabinoids include, but are not limited to, cannabidiol (CBD) and tetrahydrocannabinol (THC).

[0147] Preferably, the at least one biologically active agent comprises an alkaloid.

[0148] More preferably, the at least one bioactive agent comprises nicotine. When the at least one bioactive agent comprises nicotine, the nicotine may be in the form of a nicotine salt. Preferably, the nicotine is in the form of nicotine base.

[0149] In oral delivery products that include a substrate, the at least one bioactive agent may include one or both of nicotine and a cannabinoid.

[0150] The substrate may include any suitable amount of at least one bioactive agent.

[0151] The amount of the at least one biologically active agent can depend on many factors, including, but not limited to, the nature of the at least one biologically active agent and the method of administration of the at least one biologically active agent.

[0152] The amount of the at least one biologically active agent present in the substrate can be selected based on the desired dosage of the biologically active agent.

[0153] The substrate may include at least one bioactive agent in an amount of at least about 0.2 weight percent, or at least about 0.5 weight percent, or at least about 1 weight percent.

[0154] The substrate may include at least one bioactive agent in an amount up to about 15 weight percent, or up to about 12 weight percent, or up to about 10 weight percent.

[0155] The substrate may include at least one bioactive agent in an amount of about 0.2 weight percent to about 15 weight percent, or about 0.2 weight percent to about 12 weight percent, or about 0.2 weight percent to about 10 weight percent.

[0156] The substrate may include at least one bioactive agent in an amount of about 0.5 weight percent to about 15 weight percent, or about 0.5 weight percent to about 12 weight percent, or about 0.5 weight percent to about 10 weight percent.

[0157] The substrate may include at least one bioactive agent in an amount of about 1 weight percent to about 15 weight percent, or about 1 weight percent to about 12 weight percent, or about 1 weight percent to about 10 weight percent.

[0158] When the at least one bioactive agent comprises nicotine, the substrate may comprise nicotine in an amount up to about 5 weight percent.

[0159] The bioactive agent may include a bioactive component and a non-bioactive component. For example, the bioactive agent may be in the form of a salt that includes a bioactive component and a non-bioactive counterion. As another example, the bioactive agent may be in the form of a complex that includes a bioactive component and a non-bioactive ligand.

[0160] The weight percentage of the bioactive material is calculated using the weight of the bioactive component of the bioactive material, not the weight of the non-bioactive component of the bioactive material. For example, if the at least one bioactive material includes nicotine in the form of a nicotine salt, the weight percentage of the at least one bioactive material is calculated using the weight of nicotine. As another example, if the at least one bioactive material includes gamma-gamma hydrochloride, the weight percentage of the at least one bioactive material is calculated using the weight of gamma-gamma.

[0161] The substrate may include a flavouring agent.

[0162] If the substrate comprises a flavouring agent, then the composition preferably comprises a flavouring agent.

[0163] Suitable flavoring agents include, but are not limited to, menthol.

[0164] The composition is releasably contained within the domains of the crosslinked silicone matrix.

[0165] The crosslinked silicone matrix may be open-celled.

[0166] The composition may be released from the domains of the crosslinked silicone matrix by the action of heat.

[0167] The composition may be released from the domains of the crosslinked silicone matrix by the action of pressure.

[0168] The composition may be released from the domains of the crosslinked silicone matrix by the action of saliva.

[0169] The composition may be a liquid or a suspension.

[0170] The substrate may comprise the composition in an amount of at least about 10 weight percent, or at least about 15 weight percent, or at least about 20 weight percent.

[0171] The substrate may comprise the composition in an amount up to about 75 weight percent, or up to about 72 weight percent, or up to about 70 weight percent.

[0172] The substrate may comprise the composition in an amount from about 10 weight percent to about 75 weight percent, or from about 10 weight percent to about 72 weight percent, or from about 10 weight percent to about 70 weight percent.

[0173] The substrate may comprise the composition in an amount from about 15 weight percent to about 75 weight percent, or from about 15 weight percent to about 72 weight percent, or from about 15 weight percent to about 70 weight percent.

[0174] The substrate may comprise the composition in an amount from about 20 weight percent to about 75 weight percent, or from about 20 weight percent to about 72 weight percent, or from about 20 weight percent to about 70 weight percent.

[0175] Aerosol-generating articles in which a substrate, such as a nicotine-containing substrate, is heated rather than combusted to generate an aerosol are known in the art. One purpose of such "heat-not-burn" aerosol-generating articles is to reduce the known harmful smoke constituents of the type produced by the combustion and pyrolytic decomposition of tobacco in conventional cigarettes.

[0176] Typically, in heated aerosol-generating articles, the aerosol is generated by the transfer of heat from a heat source to a physically separate substrate. During use, volatile compounds are released and entrained in the air drawn through the aerosol-generating article. As the released compounds cool, they condense to form an aerosol that can be inhaled by the user.

[0177] The present invention relates to an aerosol-generating article comprising a substrate according to the present invention.

[0178] The aerosol-generating article may comprise a heating element configured to heat the aerosol-generating substrate.

[0179] The aerosol-generating article may be configured for use with an aerosol-generating device. The aerosol-generating device may comprise a heating element configured to heat a substrate of the aerosol-generating article.

[0180] The heating elements of one or both of the aerosol-generating article and the aerosol-generating device may include one or more resistive heating elements, one or more inductive heating elements, or a combination thereof.

[0181] The present invention relates to a transdermal patch comprising a substrate according to the present invention.

[0182] The transdermal patch may include a backing layer. The substrate may be attached to the backing layer.

[0183] The transdermal patch may include an adhesive layer. The substrate may be positioned between the backing layer and the adhesive layer.

[0184] The present invention relates to oral delivery products comprising a substrate according to the present invention. Examples of oral delivery products according to the present invention include, but are not limited to, oral chews, oral lozenges, and oral pouch products.

[0185] The present invention relates to a method for producing a substrate according to the present invention.

[0186] Preferably, the method includes mixing a silicone polymer with at least one monomeric glycol to form an emulsion. The method may further include combining the emulsion with at least one bioactive agent and at least one crosslinker comprising a tetraalkoxysilane to form a mixture.

[0187] Mixing the silicone polymer and at least one monomeric glycol to form an emulsion prior to combining the emulsion with the at least one biologically active agent and at least one crosslinker may advantageously result in a more homogenous mixture, which may advantageously contribute to the formation of a substrate having a uniformly dispersed composition, which may advantageously facilitate the manufacture of the substrate.

[0188] The method can include combining a curing catalyst with a silicone polymer, at least one monomeric glycol, at least one biologically active agent, and at least one crosslinker to form a mixture.

[0189] When the method includes mixing the silicone polymer and the at least one monomeric glycol to form an emulsion prior to combining the emulsion with the at least one biologically active material and the at least one crosslinking agent, the method can include mixing a curing catalyst with the emulsion, the at least one crosslinking agent, and the at least one biologically active material to form a mixture.

[0190] The method may include curing the mixture at room temperature.

[0191] As used herein in connection with the present invention, the term "room temperature" is used to describe a temperature between about 20 degrees Celsius and about 30 degrees Celsius. EXAMPLES

[0192] The following provides a non-exhaustive list of non-limiting examples, any one or more of the features of which may be combined with any one or more features of another example, embodiment, or aspect described herein.

[0193] Example 1: 1. A substrate for delivering a bioactive agent, comprising: a crosslinked silicone matrix formed by crosslinking a silicone polymer using at least one crosslinking agent comprising a tetraalkoxysilane, the crosslinked silicone matrix defining a plurality of domains; A composition contained within domains of a crosslinked silicone matrix, comprising: at least one monomeric glycol, and a composition comprising at least one bioactive agent; and a substrate. Example 2: The substrate of example 1, wherein the silicone polymer comprises a hydroxyl-terminated silicone polymer. Example 3: The substrate of Example 1 or Example 2, wherein the silicone polymer comprises a hydroxyl-terminated polydialkylsiloxane. Example 4: The substrate of any one of Examples 1-3, wherein the silicone polymer comprises hydroxyl-terminated polydimethylsiloxane. Example 5: The substrate of any one of Examples 1-3, wherein the silicone polymer comprises hydroxyl-terminated polydiethylsiloxane. Example 6: The substrate of Example 1 or Example 2, wherein the silicone polymer comprises a hydroxyl-terminated polydiphenylsiloxane. Example 7: The substrate of any one of Examples 1-6, wherein the silicone polymer has a molecular weight of at least about 25,000 grams / mole. Example 8: The substrate of any one of Examples 1-7, wherein the silicone polymer has a molecular weight of at least about 30,000 grams / mole. Example 9: The substrate of any one of Examples 1-8, wherein the silicone polymer has a molecular weight of at least about 35,000 grams / mole. Example 10: The substrate of any one of Examples 1-9, wherein the silicone polymer has a molecular weight of up to about 60,000 grams / mole. Example 11: The substrate of any one of Examples 1-10, wherein the silicone polymer has a molecular weight of up to about 55,000 grams / mole. Example 12: The substrate of any one of Examples 1-11, wherein the silicone polymer has a molecular weight of up to about 50,000 grams / mole. Example 13: The substrate of any one of Examples 1-12, wherein the silicone polymer is used in an amount of at least about 35 weight percent. Example 14: The substrate of any one of Examples 1-13, wherein the silicone polymer is used in an amount of at least about 40 weight percent. Example 15: The substrate of any one of Examples 1-14, wherein the silicone polymer is used in an amount of at least about 45 weight percent. Example 16: The substrate of any one of Examples 1-15, wherein the silicone polymer is used in an amount up to about 85 weight percent. Example 17: The substrate of any one of Examples 1-16, wherein the silicone polymer is used in an amount up to about 80 weight percent. Example 18: The substrate of any one of Examples 1-17, wherein the silicone polymer is used in an amount up to about 75 weight percent. Example 19: The substrate of any one of Examples 1-18, wherein at least one crosslinker is selected from the group consisting of TEOS, silicon glycerate, and silicon 1,2-propylene glycolate. Example 20: The substrate of any one of Examples 1-19, wherein at least one crosslinker comprises one or both of silicon glycerate and silicon 1,2-propylene glycolate. Example 21: The substrate of any one of Examples 1-20, wherein at least one crosslinker comprises silicon glycerate. Example 22: The substrate of Example 21, wherein silicon glycerate is used in a solution containing glycerol. Example 23: The substrate of Example 22, wherein the molar ratio of silicon glycerate to glycerol in the solution is from about 1:0.5 to about 1:2.9. Example 24: The substrate of any one of Examples 1-23, wherein at least one crosslinker comprises 1,2-propylene glycolate. Example 25: The substrate as described in Example 24, wherein the 1,2-propylene glycolate silicon is used in a solution containing 1,2-propylene glycol. Example 26: The substrate of Example 25, wherein the molar ratio of silicon 1,2-propylene glycolate to 1,2-propylene glycol in the solution is from about 1:0.5 to about 1:2.9. Example 27: The substrate of any one of Examples 1-26, wherein the molar ratio of the at least one crosslinker to the silicone polymer is at least about 1:2. Example 28: The substrate of any one of Examples 1-27, wherein an excess of at least one crosslinking agent is used to crosslink the silicone polymer. Example 29: The substrate of any one of Examples 1-28, wherein the molar ratio of the at least one crosslinker to the silicone polymer is at least about 1:1. Example 30: The substrate of any one of Examples 1-29, wherein the molar ratio of the at least one crosslinker to the silicone polymer is at least about 2:1. Example 31: The substrate of any one of Examples 1-30, wherein the molar ratio of the at least one crosslinker to the silicone polymer is up to about 45:1. Example 32: The substrate of any one of Examples 1-31, wherein the molar ratio of the at least one crosslinker to the silicone polymer is up to about 40:1. Example 33: The substrate of any one of Examples 1-32, wherein the molar ratio of the at least one crosslinker to the silicone polymer is up to about 35:1. Example 34: The substrate of any one of Examples 1-33, wherein the at least one crosslinker comprises TEOS, and the molar ratio of TEOS to silicon polymer is at least about 5:1. Example 35: The substrate of any one of Examples 1-34, wherein at least one crosslinker comprises TEOS, and the molar ratio of TEOS to silicon polymer is up to about 35:1. Example 36: The substrate of any one of Examples 1-35, wherein the at least one crosslinker comprises silicon glycerate, and the molar ratio of silicon glycerate to silicone polymer is at least about 5:1. Example 37: The substrate of any one of Examples 1-36, wherein at least one crosslinker comprises silicon glycerate and the molar ratio of silicon glycerate to silicone polymer is up to about 20:1. Example 38: The substrate of any one of Examples 1-37, wherein at least one crosslinker comprises silicon 1,2-propylene glycolate, and the molar ratio of silicon 1,2-propylene glycolate to silicone polymer is at least about 2:1. Example 39: The substrate of any one of Examples 1-38, wherein at least one crosslinker comprises silicon 1,2-propylene glycolate, and the molar ratio of silicon 1,2-propylene glycolate to silicone polymer is up to about 5:1. Example 40: The substrate of any one of Examples 1-39, wherein the substrate comprises silicon dioxide. Example 41: The substrate of any one of Examples 1-40, wherein the at least one crosslinking agent is used in an amount of at least about 0.5 weight percent. Example 42: The substrate of any one of Examples 1-41, wherein the at least one crosslinking agent is used in an amount of at least about 0.75 weight percent. Example 43: The substrate of any one of Examples 1-42, wherein the at least one crosslinking agent is used in an amount of at least about 1 weight percent. Example 44: The substrate of any one of Examples 1-43, wherein the at least one crosslinking agent is used in an amount up to about 18 weight percent. Example 45: The substrate of any one of Examples 1-44, wherein the at least one crosslinking agent is used in an amount up to about 15 weight percent. Example 46: The substrate of any one of Examples 1-45, wherein the at least one crosslinking agent is used in an amount up to about 12 weight percent. Example 47: The substrate of any one of Examples 1-46, wherein the monomeric glycol contains up to seven carbon atoms. Example 48: The substrate of any one of Examples 1-47, wherein the monomeric glycol contains at least two carbon atoms. Example 49: The substrate of any one of Examples 1-48, wherein the monomeric glycol contains from 2 carbon atoms to 6 carbon atoms. Example 50: The substrate of any one of Examples 1-49, wherein the monomeric glycol contains from 2 carbon atoms to 5 carbon atoms. Example 51: The substrate of any one of Examples 1-50, wherein the monomeric glycol contains from 2 carbon atoms to 4 carbon atoms. Example 52: The substrate of any one of Examples 1 to 51, wherein the monomeric glycol contains from 2 carbon atoms to 3 carbon atoms. Example 53: The substrate of any one of Examples 1-52, wherein the monomeric glycol contains at least three carbon atoms. Example 54: The substrate of any one of Examples 1-48 or Example 53, wherein the monomeric glycol contains from 3 carbon atoms to 7 carbon atoms. Example 55: The substrate of any one of Examples 1-49, 53 or 54, wherein the monomeric glycol contains from 3 carbon atoms to 6 carbon atoms. Example 56: The substrate of any one of Examples 1-50 or any one of Examples 53-55, wherein the monomeric glycol contains from 3 carbon atoms to 5 carbon atoms. Example 57: The substrate of any one of Examples 1-51 or any one of Examples 53-56, wherein the monomeric glycol contains from 3 carbon atoms to 4 carbon atoms. Example 58: The substrate of any one of Examples 1-57, wherein the monomeric glycol contains three carbon atoms. Example 59: The substrate of any one of Examples 1-58, wherein the at least one monomeric glycol comprises one or both of glycerol and 1,2-propylene glycol. Example 60: The substrate of any one of Examples 1-59, wherein the at least one monomeric glycol comprises glycerol. Example 61: The substrate of any one of Examples 1-60, wherein the at least one monomeric glycol comprises 1,2-propylene glycol. Example 62: The substrate of any one of Examples 1-61, wherein the substrate comprises at least one monomeric glycol in an amount of at least about 10 weight percent. Example 63: The substrate of any one of Examples 1-62, wherein the substrate comprises at least one monomeric glycol in an amount of at least about 15 weight percent. Example 64: The substrate of any one of Examples 1-63, wherein the substrate comprises at least one monomeric glycol in an amount of at least about 20 weight percent. Example 65: The substrate of any one of Examples 1-64, wherein the substrate comprises at least one monomeric glycol in an amount up to about 60 weight percent. Example 66: The substrate of any one of Examples 1-65, wherein the substrate comprises at least one monomeric glycol in an amount up to about 55 weight percent. Example 67: The substrate of any one of Examples 1-66, wherein the substrate comprises at least one monomeric glycol in an amount up to about 50 weight percent. Example 68: The substrate of any one of Examples 1-67, wherein the substrate comprises glycerol and 1,2-propylene glycol in a ratio of greater than about 1:1 by weight. Example 69: The substrate of any one of Examples 1-68, wherein the substrate comprises both glycerol and 1,2-propylene glycol, and the substrate comprises about the same amount of glycerol by weight as 1,2-propylene glycol. Example 70: The substrate of any one of Examples 1-68, wherein the substrate comprises both glycerol and 1,2-propylene glycol, and the substrate comprises more glycerol by weight than 1,2-propylene glycol. Example 71: The substrate of any one of Examples 1-70, wherein the substrate comprises both glycerol and 1,2-propylene glycol, the substrate comprising glycerol and 1,2-propylene glycol in a ratio of at least about 1:1 by weight. Example 72: The substrate of any one of Examples 1-71, wherein the substrate comprises both glycerol and 1,2-propylene glycol, the substrate comprising glycerol and 1,2-propylene glycol in a weight ratio of at least about 1.5:1. Example 73: The substrate of any one of Examples 1-72, wherein the substrate comprises both glycerol and 1,2-propylene glycol, the substrate comprising glycerol and 1,2-propylene glycol in a ratio of at least about 2:1 by weight. Example 74: The substrate of any one of Examples 1-73, wherein the substrate comprises both glycerol and 1,2-propylene glycol, the substrate comprising glycerol and 1,2-propylene glycol in a ratio of up to about 59:1 by weight. Example 75: The substrate of any one of Examples 1-74, wherein the substrate comprises both glycerol and 1,2-propylene glycol, the substrate comprising glycerol and 1,2-propylene glycol in a ratio of up to about 40:1 by weight. Example 76: The substrate of any one of Examples 1-75, wherein the substrate comprises both glycerol and 1,2-propylene glycol, the substrate comprising glycerol and 1,2-propylene glycol in a ratio of up to about 25:1 by weight. Example 77: The substrate of any one of Examples 1 to 76, wherein the substrate comprises polyethylene oxide. Example 78: The substrate of any one of Examples 1-77, wherein the substrate comprises polyethylene oxide in an amount less than about 1 weight percent. Example 79: The substrate of any one of Examples 1-78, wherein the substrate comprises polyethylene oxide in an amount less than about 0.5 weight percent. Example 80: The substrate of any one of Examples 1-79, wherein the substrate comprises polyethylene oxide in an amount less than about 0.1 weight percent. Example 81: The substrate of any one of Examples 1 to 76, wherein the substrate does not contain polyethylene oxide. Example 82: The substrate of any one of Examples 1 to 81, wherein the substrate comprises a fatty acid. Example 83: The substrate of any one of Examples 1-82, wherein the substrate comprises a fatty acid in an amount less than about 1 weight percent. Example 84: The substrate of any one of Examples 1-83, wherein the substrate comprises a fatty acid in an amount less than about 0.5 weight percent. Example 85: The substrate of any one of Examples 1-84, wherein the substrate comprises a fatty acid in an amount less than about 0.1 weight percent. Example 86: The substrate of any one of Examples 82 to 85, wherein the fatty acid comprises linoleic acid. Example 87: The substrate of any one of Examples 82 to 86, wherein the fatty acid comprises oleic acid. Example 88: The substrate of any one of Examples 1-85 or Example 87, wherein the substrate does not contain linoleic acid. Example 89: The substrate of any one of Examples 1-86 or 88, wherein the substrate does not contain oleic acid. Example 90: The substrate of any one of Examples 1 to 81, wherein the substrate does not contain a fatty acid. Example 91: The substrate of any one of Examples 1 to 90, wherein the substrate comprises a curing catalyst. Example 92: The substrate of any one of Examples 1 through 91, wherein the substrate comprises a cure catalyst in an amount of at least about 0.2 weight percent. Example 93: The substrate of any one of Examples 1 through 92, wherein the substrate comprises a cure catalyst in an amount of at least about 0.5 weight percent. Example 94: The substrate of any one of Examples 1 through 93, wherein the substrate comprises a cure catalyst in an amount of at least about 0.8 weight percent. Example 95: The substrate of any one of Examples 1-94, wherein the substrate comprises a cure catalyst in an amount up to about 12 weight percent. Example 96: The substrate of any one of Examples 1 through 95, wherein the substrate comprises a cure catalyst in an amount up to about 10 weight percent. Example 97: The substrate of any one of Examples 1 through 96, wherein the substrate comprises a cure catalyst in an amount up to about 8 weight percent. Example 98: The substrate of any one of Examples 1-97, wherein the crosslinked silicone matrix is ​​formed by crosslinking a silicone polymer in the presence of a curing catalyst. Example 99: The substrate of any one of Examples 1-98, wherein the cure catalyst is present during the formation of the crosslinked silicone matrix in an amount of at least about 0.2 weight percent. Example 100: The substrate of any one of Examples 1 through 99, wherein the cure catalyst is present during formation of the crosslinked silicone matrix in an amount of at least about 0.5 weight percent. Example 101: The substrate of any one of Examples 1-100, wherein the cure catalyst is present during formation of the crosslinked silicone matrix in an amount of at least about 0.8 weight percent. Example 102: The substrate of any one of Examples 1-101, wherein a cure catalyst is present during formation of the crosslinked silicone matrix in an amount up to about 12 weight percent. Example 103: The substrate of any one of Examples 1-102, wherein a cure catalyst is present during formation of the crosslinked silicone matrix in an amount up to about 10 weight percent. Example 104: The substrate of any one of Examples 1-103, wherein a cure catalyst is present during formation of the crosslinked silicone matrix in an amount up to about 8 weight percent. Example 105: The substrate of any one of Examples 91-104, wherein the curing catalyst comprises a room temperature vulcanization catalyst. Example 106: The substrate of any one of Examples 91-105, wherein the curing catalyst comprises at least one of an aminopropyl-terminated silicone polymer, an amine, and a metal-based catalyst. Example 107: The substrate of any one of Examples 91-106, wherein the cure catalyst comprises an aminopropyl-terminated silicone polymer. Example 108: The substrate of any one of Examples 91-107, wherein the cure catalyst comprises an aminopropyl-terminated polydimethylsiloxane. Example 109: The substrate of any one of Examples 91-108, wherein the cure catalyst comprises an aminopropyl terminated silicone polymer, the aminopropyl terminated silicone polymer having a molecular weight of at least about 400 grams / mole. Example 110: The substrate of any one of Examples 91-109, wherein the cure catalyst comprises an aminopropyl terminated silicone polymer, the aminopropyl terminated silicone polymer having a molecular weight of at least about 600 grams / mole. Example 111: The substrate of any one of Examples 91-110, wherein the cure catalyst comprises an aminopropyl terminated silicone polymer, the aminopropyl terminated silicone polymer having a molecular weight of at least about 800 grams / mole. Example 112: The substrate of any one of Examples 91-111, wherein the cure catalyst comprises an aminopropyl terminated silicone polymer, the aminopropyl terminated silicone polymer having a molecular weight of up to about 3000 grams / mole. Example 113: The substrate of any one of Examples 91-112, wherein the cure catalyst comprises an aminopropyl terminated silicone polymer, the aminopropyl terminated silicone polymer having a molecular weight of up to about 2800 grams / mole. Example 114: The substrate of any one of Examples 91-113, wherein the cure catalyst comprises an aminopropyl terminated silicone polymer, the aminopropyl terminated silicone polymer having a molecular weight of up to about 2600 grams / mole. Example 115: The substrate of any one of Examples 91 to 114, wherein the curing catalyst comprises an amine. Example 116: The substrate of any one of Examples 91 to 115, wherein the curing catalyst comprises a monoamine. Example 117: The substrate of any one of Examples 91 to 116, wherein the curing catalyst comprises monoethanolamine. Example 118: The substrate of any one of Examples 91 to 116, wherein the curing catalyst comprises a diamine. Example 119: The substrate of any one of Examples 91-117, wherein the cure catalyst comprises 1,6-hexamethylenediamine. Example 120: The substrate of any one of Examples 91 to 119, wherein the curing catalyst comprises a metal-based catalyst. Example 121: The substrate of any one of Examples 91 to 120, wherein the curing catalyst comprises dibutyltin dilaurate. Example 122: The substrate of any one of Examples 91-121, wherein the cure catalyst comprises tin(II) octoate. Example 123: The substrate of any one of Examples 1-122, wherein the at least one biologically active agent comprises an alkaloid. Example 124: The substrate of any one of Examples 1-123, wherein the at least one biologically active agent comprises nicotine. Example 125: The substrate of Example 124, wherein the nicotine is in the form of a nicotine salt. Example 126: The substrate of Example 124, wherein the nicotine is in the form of nicotine base. Example 127: The substrate of any one of Examples 1 to 126, wherein the at least one bioactive agent comprises a cannabinoid. Example 128: The substrate of any one of Examples 1-127, wherein the at least one biologically active agent comprises diclofenac sodium. Example 129: The substrate of any one of Examples 1-128, wherein the at least one biologically active agent comprises gangulfen hydrochloride. Example 130: The substrate of any one of Examples 1-129, wherein the at least one biologically active agent comprises furazolidone. Example 131: The substrate of any one of Examples 1-130, wherein the substrate comprises at least one bioactive agent in an amount of at least about 0.2 weight percent. Example 132: The substrate of any one of Examples 1-131, wherein the substrate comprises at least one bioactive agent in an amount of at least about 0.5 weight percent. Example 133: The substrate of any one of Examples 1-132, wherein the substrate comprises at least one bioactive agent in an amount of at least about 1 weight percent. Example 134: The substrate of any one of Examples 1-133, wherein the substrate comprises at least one bioactive agent in an amount up to about 15 weight percent. Example 135: The substrate of any one of Examples 1-134, wherein the substrate comprises at least one bioactive agent in an amount up to about 12 weight percent. Example 136: The substrate of any one of Examples 1-135, wherein the substrate comprises at least one bioactive agent in an amount up to about 10 weight percent. Example 137: The substrate of any one of Examples 1-136, wherein the at least one biologically active agent comprises nicotine, and the substrate comprises nicotine in an amount up to about 5 weight percent. Example 138: The substrate of any one of Examples 1 to 137, wherein the substrate comprises a flavoring agent. Example 139: The substrate of any one of Examples 1 to 138, wherein the composition comprises a flavoring agent. Example 140: The substrate of Example 138 or Example 141, wherein the flavoring agent comprises menthol. Example 141: The substrate of any one of Examples 1-140, wherein the composition is releasably contained within the domains of a crosslinked silicone matrix. Example 142: The substrate of any one of Examples 1 to 141, wherein the composition is a liquid. Example 143: The substrate of any one of Examples 1 to 141, wherein the composition is a suspension. Example 144: The substrate of any one of Examples 1 through 143, wherein the substrate comprises the composition in an amount of at least about 10 weight percent. Example 145: The substrate of any one of Examples 1 through 144, wherein the substrate comprises the composition in an amount of at least about 15 weight percent. Example 146: The substrate of any one of Examples 1 through 145, wherein the substrate comprises the composition in an amount of at least about 20 weight percent. Example 147: The substrate of any one of Examples 1 through 146, wherein the substrate comprises the composition in an amount up to about 75 weight percent. Example 148: The substrate of any one of Examples 1 through 147, wherein the substrate comprises the composition in an amount up to about 72 weight percent. Example 149: The substrate of any one of Examples 1 through 148, wherein the substrate comprises the composition in an amount up to about 70 weight percent. Example 150: An aerosol-generating article comprising a substrate according to any one of Examples 1 to 149. Example 151: The aerosol-generating article of example 150, wherein the aerosol-generating article comprises a heating element configured to heat the aerosol-generating substrate. Example 152: The aerosol-generating article of example 151, wherein the heating element comprises one or more resistive heating elements. Example 153: The aerosol-generating article of example 151 or example 152, wherein the heating element comprises one or more induction heating elements. Example 154: An aerosol-generating article according to any one of Examples 150 to 153, wherein the aerosol-generating article is configured to be used together with an aerosol generating device. Example 155: The aerosol-generating article of example 154, wherein the aerosol-generating device comprises a heating element configured to heat a substrate of the aerosol-generating article. Example 156: 156. The aerosol-generating article of embodiment 155, wherein the heating element of the aerosol generating device comprises one or more resistive heating elements. Example 157: An aerosol-generating article as described in example 155 or example 156, wherein the heating element of the aerosol-generating device includes one or more induction heating elements. Example 158: A transdermal patch comprising the substrate described in any one of Examples 1 to 149. Example 159: The transdermal patch of Example 158, wherein the transdermal patch comprises a backing layer. Example 160: The transdermal patch of Example 159, wherein the substrate is attached to a backing layer. Example 161: The transdermal patch described in any one of Examples 158 to 160, wherein the transdermal patch comprises an adhesive layer. Example 162: The transdermal patch described in any one of Examples 158 to 161, wherein the transdermal patch comprises a backing layer and an adhesive layer, and the substrate is positioned between the backing layer and the adhesive layer. Example 163: An oral delivery product comprising a substrate as described in any one of Examples 1 to 149. Example 164: The oral delivery product of Example 163, wherein the oral delivery product is an oral chew. Example 165: The oral delivery product of Example 163, wherein the oral delivery product is an oral lozenge. Example 166: The oral delivery product of Example 163, wherein the oral delivery product is an oral pouch product. Example 167: The oral delivery product of any one of Examples 163 to 166, wherein the at least one biologically active agent comprises nicotine. Example 168: The oral delivery product of any one of Examples 163 to 167, wherein the at least one biologically active agent comprises a cannabinoid. Example 169: A method of making a substrate for delivering a biologically active material as described in any one of Examples 1-149, the method comprising: mixing a silicone polymer, at least one monomeric glycol, at least one biologically active material, and at least one crosslinker comprising a tetraalkoxysilane to form a mixture; and curing the mixture to form the substrate. Example 170: The method of example 169, wherein the method comprises mixing a silicone polymer and at least one monomeric glycol to form an emulsion. Example 171: The method of example 170, wherein the method further comprises combining the emulsion with at least one biologically active agent and at least one crosslinker comprising a tetraalkoxysilane to form a mixture. Example 172: The method of any one of Examples 169 to 171, comprising mixing a curing catalyst with a silicone polymer, at least one monomeric glycol, at least one biologically active agent, and at least one crosslinker to form a mixture. Example 173: The method of example 170 or example 171, the method comprising mixing a curing catalyst with the emulsion, the at least one crosslinking agent, and the at least one biologically active agent to form a mixture. Example 174: The method of any one of examples 169 to 173, wherein the method comprises curing the mixture at room temperature.

[0194] Seventeen substrates according to the present invention (Examples 1-17) were prepared using a silicone polymer, at least one crosslinking agent, at least one monomeric glycol, at least one biologically active agent, and a curing catalyst.

[0195] To form the substrate, the silicone polymer and at least one monomeric glycol are mixed in a glass beaker to form a smooth emulsion. At least one crosslinker, a curing catalyst, and at least one bioactive agent are added to the emulsion. The resulting mixture is cured at room temperature to form a substrate comprising a crosslinked silicone matrix and a composition contained within domains of the crosslinked silicone matrix.

[0196] Table 1 shows the silicone polymer, at least one crosslinker, at least one monomeric glycol, at least one bioactive agent, a cure catalyst, and the amounts of these components used to form the substrates of Examples 1-6.

[0197] In Examples 1-3, the hydroxyl-terminated polydimethylsiloxane (PDMS-OH) was provided by Aldrich and has a viscosity of 2550-3570 centistokes.

[0198] In Example 4, the hydroxyl-terminated polydimethylsiloxane (PDMS-OH) was provided by Gelest and has a viscosity of 3500 centistokes.

[0199] In Examples 5 and 6, the hydroxyl-terminated polydimethylsiloxane (PDMS-OH) was provided by Gelest and has a viscosity of 2000 centistokes.

[0200] In Examples 3 and 6, silicon glycerate (Si-GLY) is present in a solution containing glycerol in a molar ratio of about 1:2.9.

[0201] In Examples 4 and 5, silicon 1,2-propylene glycolate (Si-PGL) is present in a solution containing 1,2-propylene glycol in a molar ratio of about 1:2.9.

[0202] In Examples 1-3, aminopropyl-terminated polydimethylsiloxane (PDMS-NH2) was provided by Aldrich and has a viscosity of 50 centistokes.

[0203] In Examples 4-6, aminopropyl-terminated polydimethylsiloxane (PDMS-NH2) was provided by Gelest and has a viscosity of 10-15 centistokes.

[0204] Table 2 shows the cure times required to vulcanize the silicone polymer to form the substrates of Examples 1-6.

[0205] The substrate of Example 1 is a dense monolith with no traces of glycerol on its outer surface.

[0206] The substrate of Example 2 is a dense bulk substrate with no traces of glycerol on the outer surface.

[0207] The substrate of Example 3 is a dense bulk substrate with no traces of glycerol on the outer surface.

[0208] The substrate of Example 4 is a dense monolith with no traces of glycerol on its outer surface.

[0209] The substrate of Example 5 is a dense bulk substrate with no traces of glycerol on the outer surface.

[0210] The substrate of Example 6 is a dense bulk substrate that does not adhere to paper.

[0211] Table 2 also shows the amount of nicotine released from the substrates of Examples 1-6 in saline at room temperature after about 5 hours and about 24 hours. The amount of nicotine released in saline is measured by UV analysis of the saline after the substrate is placed in the saline for the specified time. The amount of nicotine released in saline is used to calculate the percentage by weight loss of nicotine in saline based on the weight of nicotine added to form the substrate. After about 24 hours, a negligible amount of nicotine is further released from the substrates of Examples 1-6 in saline.

[0212] Table 2 also shows the release of nicotine from the substrates of Examples 1 and 2 in an air stream heated to a temperature of about 200°C after about 10 minutes. When the substrate of Example 1 is heated to about 200°C, nicotine is released in an aerosol containing glycerol. When the substrate of Example 2 is heated to about 200°C, nicotine is released in an aerosol containing both glycerol and 1,2-propylene glycol. The release of nicotine in the heated air stream is calculated by placing a substrate that has been subjected to an air stream heated to a temperature of about 200°C for about 10 minutes in saline at room temperature, measuring the amount of nicotine released in the saline by UV analysis after about 24 hours, and subtracting the amount of nicotine released in the saline from the amount of nicotine used to form the substrate. The calculated amount of nicotine released in the heated air stream is used to calculate the percent reduction in nicotine by weight in the heated air stream based on the weight of nicotine used to form the substrate.

[0213] Table 2 also shows the weight loss measured by thermogravimetric analysis combined with mass spectrometry (TGA-MS) of the substrates of Examples 1-3 and 5 when heated to a temperature of about 300° C. The weight loss of the substrates of Examples 1 and 3 is due to the release of nicotine and glycerol. The weight loss of the substrates of Examples 2 and 5 is due to the release of nicotine, glycerol and 1,2-propylene glycol.

[0214] Table 2 also shows the Young's modulus of the substrates of Examples 1 and 2 as measured using a tensile test. [Table 1] [Table 2]

[0215] Table 3 shows the silicone polymer, at least one crosslinker, at least one monomeric glycol, at least one bioactive agent, cure catalyst, and the amounts of these components used to form the substrates of Examples 7-10.

[0216] In Examples 7-10, the hydroxyl-terminated polydimethylsiloxane (PDMS-OH) was provided by Gelest and has a viscosity of 2000 centistokes.

[0217] In Example 8, silicon 1,2-propylene glycolate (Si-PGL) is present in a solution containing 1,2-propylene glycol in a molar ratio of about 1:2.9.

[0218] In Example 9, silicon glycerate (Si-GLY) is present in a solution containing glycerol in a molar ratio of about 1:2.9.

[0219] In Examples 7-10, aminopropyl-terminated polydimethylsiloxane (PDMS-NH2) was provided by Gelest and has a viscosity of 10-15 centistokes.

[0220] Table 4 shows the cure times required to vulcanize the silicone polymers to form the substrates of Examples 7-10.

[0221] The substrate of Example 7 is a dense bulk substrate that does not adhere to paper.

[0222] The substrate of Example 8 is a dense bulk substrate that does not adhere to paper.

[0223] The substrate of Example 9 is a dense bulk substrate that does not adhere to paper.

[0224] The substrate of Example 10 is a dense bulk substrate that does not adhere to paper.

[0225] Table 4 shows the amount of diclofenac sodium released from the substrates of Examples 7-9 in ethanol at room temperature after about 5 hours and about 24 hours. The amount of diclofenac sodium released in ethanol is measured by UV analysis of the ethanol after the substrate is placed in ethanol for the specified time. The amount of diclofenac sodium released in ethanol is used to calculate the percentage weight loss of diclofenac sodium in ethanol based on the total amount of diclofenac sodium added to form the substrate.

[0226] Table 4 also shows the amount of diclofenac sodium released from the substrates of Examples 7-10 in saline at room temperature after about 5 hours, about 24 hours, and about 8 days. The amount of diclofenac sodium released in saline is measured by UV analysis of the saline after the substrate is placed in the saline for the specified period of time. The amount of diclofenac sodium released in saline is used to calculate the percentage by weight loss of diclofenac sodium in saline based on the total amount of diclofenac sodium added to form the substrate. [Table 3] [Table 4]

[0227] Table 5 shows the silicone polymer, at least one crosslinker, at least one monomeric glycol, at least one bioactive agent, cure catalyst, and the amounts of these components used to form the substrates of Examples 11-15.

[0228] In Examples 11-14, the hydroxyl-terminated polydimethylsiloxane (PDMS-OH) was provided by Gelest and has a viscosity of 2000 centistokes.

[0229] In Example 15, the hydroxyl-terminated polydimethylsiloxane (PDMS-OH) was provided by Gelest and has a viscosity of 5000 centistokes.

[0230] In Examples 12 and 15, silicon 1,2-propylene glycolate (Si-PGL) is present in a solution containing 1,2-propylene glycol in a molar ratio of about 1:2.9.

[0231] In Example 13, silicon glycerate (Si-GLY) is present in a solution containing glycerol in a molar ratio of about 1:2.9.

[0232] In Examples 11-15, aminopropyl-terminated polydimethylsiloxane (PDMS-NH2) was provided by Gelest and has a viscosity of 10-15 centistokes.

[0233] Table 6 shows the cure times required to vulcanize the silicone polymers to form the substrates of Examples 11-15.

[0234] The substrate of Example 11 is elastic and tacky, and adheres strongly to paper.

[0235] The substrate of Example 12 is slightly tacky and has poor adhesion to paper.

[0236] The substrate of Example 13 is slightly tacky but does not adhere to paper.

[0237] The substrate of Example 14 is elastic, slightly tacky, and has poor adhesion to paper.

[0238] The substrate of Example 15 is elastic, slightly tacky, and has poor adhesion to paper.

[0239] Table 6 shows the amount of ganglufen hydrochloride released from the substrates of Examples 11-15 in saline at room temperature after about 5 hours, about 24 hours, and about 8 days. The amount of ganglufen hydrochloride released in saline is measured by UV analysis of the saline after the substrate is placed in saline for the specified period of time. The amount of ganglufen hydrochloride released in saline is used to calculate the percentage by weight loss of ganglufen hydrochloride in saline based on the weight of ganglufen hydrochloride added to form the substrate. [Table 5] [Table 6]

[0240] Table 7 shows the silicone polymer, at least one crosslinker, at least one monomeric glycol, at least one bioactive agent, cure catalyst, and the amounts of these components used to form the substrates of Examples 16 and 17.

[0241] In Examples 16 and 17, the hydroxyl-terminated polydimethylsiloxane (PDMS-OH) was provided by Gelest and has a viscosity of 2000 centistokes.

[0242] In Example 16, silicon 1,2-propylene glycolate (Si-PGL) is present in a solution containing 1,2-propylene glycol in a molar ratio of about 1:2.9.

[0243] In Example 17, silicon glycerate (Si-GLY) is present in a solution containing glycerol in a molar ratio of about 1:2.9.

[0244] In Examples 16 and 17, aminopropyl-terminated polydimethylsiloxane (PDMS-NH2) was provided by Gelest and has a viscosity of 10-15 centistokes.

[0245] Table 8 shows the cure times required to vulcanize the silicone polymers to form the substrates of Examples 16 and 17.

[0246] The substrate of Example 16 is elastic, non-tacky, and has poor adhesion to paper.

[0247] The substrate of Example 17 is elastic, non-tacky, and has poor adhesion to paper.

[0248] Table 8 also shows the amount of furazolidone released from the substrates of Examples 16 and 17 in saline at room temperature after about 5 hours, about 24 hours, and about 8 days. The amount of furazolidone released in saline is measured by UV analysis of the saline after the substrates are placed in the saline for the specified period of time. The amount of furazolidone released in saline is used to calculate the percentage by weight loss of furazolidone in the saline based on the weight of furazolidone added to form the substrate. [Table 7] [Table 8]

[0249] The invention will now be further described, by way of example only, with reference to the accompanying drawings in which:

[0250] FIG. 1 shows a schematic cross-sectional side view of an aerosol-generating article including a substrate according to the present invention.

[0251] FIG. 2 shows a schematic side cross-sectional view of a transdermal patch including a substrate according to the present invention.

[0252] FIG. 1 shows an aerosol-generating article 10 including a substrate 12 , an air inlet 14 , and an air outlet 16 .

[0253] 2 shows a transdermal patch 20 comprising a substrate 22, a backing layer 24, and an adhesive layer 26. The substrate 22 is positioned between the backing layer 24 and the adhesive layer 26.

[0254] The specific embodiments and examples described above are illustrative of the invention but do not limit it, it being understood that other embodiments of the invention may be made and that the specific embodiments and examples described herein are not exhaustive.

Claims

1. 1. A substrate for delivering a bioactive agent, comprising: a crosslinked silicone matrix formed by crosslinking a silicone polymer using at least one crosslinking agent comprising a tetraalkoxysilane, the crosslinked silicone matrix defining a plurality of domains; a composition contained within said domains of said crosslinked silicone matrix, said composition comprising at least one monomeric glycol and at least one biologically active agent; The substrate comprising:

2. The substrate of claim 1, wherein the at least one crosslinking agent is selected from the group consisting of TEOS, silicon glycerate, and silicon 1,2-propylene glycolate.

3. The substrate of claim 2, wherein the at least one crosslinker comprises one or both of silicon glycerate and silicon 1,2-propylene glycolate.

4. The substrate of any one of claims 1 to 3, wherein the at least one crosslinking agent is used in an amount of from about 0.2 weight percent to about 18 weight percent.

5. The substrate of any one of claims 1 to 3, wherein the at least one monomeric glycol comprises one or both of glycerol and 1,2-propylene glycol.

6. The substrate of any one of claims 1 to 3, wherein said substrate comprises said at least one monomeric glycol in an amount of from about 10 weight percent to about 60 weight percent.

7. The substrate of any one of claims 1 to 3, wherein the silicone polymer comprises a hydroxyl-terminated silicone polymer.

8. The substrate of claim 7 , wherein the silicone polymer comprises hydroxyl-terminated polydimethylsiloxane.

9. The substrate of any one of claims 1 to 3, wherein the silicone polymer is used in an amount of about 35 weight percent to about 85 weight percent.

10. The substrate of any one of claims 1 to 3, wherein the substrate comprises a curing catalyst.

11. The substrate of claim 10 , wherein the cure catalyst comprises at least one of an aminopropyl-terminated silicone polymer, an amine, and a metal-based catalyst.

12. The substrate of claim 10, wherein the substrate comprises the curing catalyst in an amount from about 0.2 weight percent to about 12 weight percent.

13. The substrate of any one of claims 1 to 3, wherein the substrate comprises the at least one bioactive agent in an amount of about 0.2 weight percent to about 15 weight percent.

14. The substrate of any one of claims 1 to 3, wherein the at least one biologically active agent comprises nicotine.

15. An aerosol-generating article comprising a substrate according to any one of claims 1 to 3.

16. A transdermal patch comprising a substrate according to any one of claims 1 to 3.

17. An oral delivery product comprising the substrate of any one of claims 1 to 3.

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