GB2625277A

GB2625277A - Patch

Info

Publication number: GB2625277A
Application number: GB2218636.5A
Authority: GB
Inventors: Fu Richard; Arnold Peter; Torun Hamdi
Original assignee: Northumbria University
Current assignee: Northumbria University
Priority date: 2022-12-12
Filing date: 2022-12-12
Publication date: 2024-06-19
Also published as: WO2024126989A1; GB202218636D0

Abstract

A patch for active substance transdermal delivery comprises at least one surface acoustic wave transducer comprising one or more electrodes 804 on a piezoelectric layer 803, and an active substance-infused layer 805 adjacent the piezoelectric layer or separated therefrom by an intermediate layer (902, Fig.9). There may be dressing 802 and protective 806 layers. The electrodes are located over the active substance infused layer such that, when the patch is on skin and the transducers energised, acoustic energy causes active substance molecule transfer through the skin. Acoustic energy temporarily disrupts the epidermal impervious layer creating micropores and is assisted by turbulence in the acoustic wave, local heating, internal streaming in the infused layer and increases in local pressure induced by the waves. Microneedles may also be provided. The electrodes may be linear or, preferably, circular interdigitating electrodes to focus acoustic energy to increase substance transfer. There may be a wired or wireless controller and the electrodes may be powered by a battery or an energy receiving antenna on the piezoelectric layer. Piezo layer strain relieving apertures (705, Fig. 7) prevent electrode flexing damage.

Description

PATCH

Technical Field

The present invention relates to patches for the transdermal delivery of active substances, and associated systems.

Background

There are several well-established routes for drug administration; each with advantages and drawbacks.

Enteral techniques involving, for example, oral or rectal administration, rely on the absorption of the active substances of drugs through the gastrointestinal tract. Enteral techniques are typically noninvasive, simple to administer and often do not require skilled supervision. However, fine dosage control can be difficult because the degree and timing of gastrointestinal drug absorption typically varies from subject to subject, and, for oral administration in particular, the active substances of some drugs are subject to first pass metabolism where the liver breaks down significant amounts of the drug before it can enter circulation.

The active substance of drugs administered by parenteral techniques on the other hand, enter the body through routes other than absorption via the gastrointestinal tract. Common examples include intramuscular or intravenous injection using a needle and syringe, and intravenous administration via a pre-inserted catheter. Because parenteral techniques do not rely on adsorption through the gastrointestinal tract (and therefore are not subject to the variability of gastrointestinal drug absorption), in many examples they allow for finer dosage control. However, parenteral techniques are often complicated and therefore require skilled supervision. Moreover, parenteral techniques are often invasive and therefore often disliked by patients.

That said, transdermal patches, where an active substance infused patch is positioned on a subject's skin, and the drug administered via absorption through the subject's skin, provide an easy to administer parenteral drug technique. However, as with enteral techniques, the degree of absorption can be variable. Moreover, certain drug compounds, particularly those where the active substances are non-oil soluble and/or have larger molecules (for example above 400 Daltons), may be subject to limited transdermal absorption or not capable of transdermal absorption at all.

Some of the drawbacks of such transdermal patches are addressed by microneedles. Microneedles are less than a millimetre long and are typically used in a patch that contains hundreds of needles. When the patch is applied to the skin, the needles puncture the skin and deliver drugs to the body. However, microneedles are a relatively recent technology, they physically puncture the skin, and the fabrication of patches including microneedle arrays is complex and expensive.

Summary of the Invention

In accordance with a first aspect of the invention, there is provided a patch for the transdermal delivery of an active substance, said patch comprising: at least one surface acoustic wave transducer comprising one or more electrodes positioned on a piezoelectric layer, and an active substance-infused layer positioned adjacent the piezoelectric layer, wherein the at least one surface acoustic wave transducer is located relative to the active substance-infused layer such that the one or more electrodes are positioned over the active substance-infused layer, such that in use when the patch is positioned on a subject's skin and when the at least one surface acoustic wave transducer is energised: acoustic energy generated by the at least one surface acoustic wave transducer gives rise to a transfer of active substance molecules infused in the active substance-infused layer into the subject's body through the subject's skin.

Optionally, the one or more electrodes are interdigitated electrodes.

Optionally, the one or more interdigitated electrodes have a circular configuration.

Optionally, the patch further comprises an energy receiving antenna coupled to the at least one surface acoustic wave transducer, wherein the at least one surface acoustic wave transducer is configured to be wirelessly energised by energy received by the energy receiving antenna.

Optionally, the piezoelectric layer is flexible such that the transdermal patch is able to conform to a profile of the subject's body in use.

Optionally, the piezoelectric layer comprises one or more strain-relieving apertures configured to reduce strain to which the at least one surface acoustic wave transducer is subject when the transdermal patch is subject to flexing.

Optionally, the patch comprises further flexible layer positioned relative to the piezoelectric layer for protecting the piezoelectric layer and the at least one surface acoustic wave transducer.

Optionally, the active substance-infused layer is removable and replaceable.

Optionally, regions of the piezoelectric layer and/or active substance-infused layer are of non-uniform density to redirect horizontal components of the acoustic energy generated by the at least one surface acoustic wave transducer in a vertical direction towards the subject's skin when in use.

In accordance with a second aspect of the invention, there is provided a drug delivery system comprising a patch in accordance with the first aspect and an energising signal generator unit connectable to the transdermal patch and configured to generate an energising signal for energising the at least one surface acoustic wave transducer of the active substance delivery patch.

Optionally, the energising signal generator unit comprises an energy harvesting power supply.

Optionally, the transdermal patch and the energising signal generator unit are integrated as a single unit.

Embodiments of the invention provide an active substance delivery technique that provides the simplicity and convenience of parenteral delivery via a transdermal patch but, because of the inclusion of a SAW (surface acoustic wave) transducer that generates acoustic energy that drives active substances into the body via the skin, also enables the transdermal delivery of treatments that can't conventionally be delivered via a transdermal patch (for example drugs with large-molecule active substances).

Moreover, advantageously, SAW-based transducers are highly adaptable. The nature of the surface acoustic waves that a SAW transducer can produce is readily changed by using different electrode geometries and/or varying the parameters, such as the wavelength, frequency, and amplitude of the driving signals. Consequently, this high degree of adaptability means that specific parameters of the SAWtransducer can be optimised for the delivery of specifictypes of drugs and forspecific drug delivery protocols.

Various further features and aspects of the invention are defined in the claims.

Brief Description of the Drawings

Embodiments of the present invention will now be described by way of example only with reference to the accompanying drawings where like parts are provided with corresponding reference numerals and in which: Figure 1 provides a simplified schematic diagram depicting use of an active substance delivery patch arranged in accordance with certain embodiments of the invention; Figure 2 provides a simplified schematic diagram depicting an exploded view of an active substance delivery patch in accordance with certain embodiments of the invention; Figure 3 provides a simplified schematic diagram depicting a cross-sectional view of an active substance delivery patch in accordance with certain embodiments of the invention; Figure 4 provides a simplified schematic diagram depicting components of an energising signal generator unit arranged in accordance with certain embodiments of the invention; Figures 5 and 6 provide views of such electrode configurations for use in a transducer array in accordance with certain embodiments of the invention; Figure 7 provides a simplified schematic diagram depicting the provision of a plurality of strain relieving apertures disposed across a piezoelectric layer and flexible intermediate substrate arranged in accordance with certain embodiments of the invention; Figure 8 provides a simplified schematic diagram depicting an exploded view of an active substance delivery patch in accordance with certain embodiments of the invention including a further protective flexible layer; Figure 9 provides a simplified schematic diagram depicting an exploded view of an active substance delivery patch in accordance with further certain embodiments of the invention including a further layer for selectively energising molecules of the active substance-infused layer, and Figure 10 provides a simplified schematic diagram depicting a piezoelectric layer in accordance with certain embodiments of the invention further comprising an energy receiving antenna.

Detailed Description

The term "active substance" refers to a substance which has a biological, chemical, or biochemical effect on the body to which it is to be applied and includes, for example, drugs and medicaments such as pharmaceutical medicines and veterinary medicines, small molecules, antibodies vaccines, genetic material such as DNA, cells and the like. In preferred embodiments, the active substance is any drug, pharmacological or therapeutic agent or combination of agents which, when delivered in a therapeutically effective amount, provide a therapeutic effect.

The term "therapeutically effective amount" means an amount of a drug or agent which is effective to achieve a desired therapeutic effect. The precise desired therapeutic effect will vary according to the condition to be treated and a variety of other factors that are known by those of ordinary skill in the art.

Figure 1 provides a simplified schematic diagram depicting use of an active substance delivery patch 101 arranged in accordance with certain embodiments of the invention.

Figure 1 shows the active substance delivery patch 101 positioned in place in the region of a subject's wrist 102. It will be understood this positioning is merely illustrative and that the active substance delivery patch 101 can be positioned in any suitable location on a subject's body for example, shoulder, back, thigh, buttocks and so on.

The active substance delivery patch 101 is connected to an energising signal generator unit 103 via a connecting lead 104.

Figure 2 provides a simplified schematic diagram depicting an exploded view showing the components of the active substance delivery patch 101.

The active substance delivery patch 101 comprises a dressing layer 201 which is located over a piezoelectric layer 202. The dressing layer 201 can be provided by any suitable medical dressing material as is well known in the art.

The piezoelectric layer 202 can be provided by any suitable piezoelectric material. In certain examples, the piezoelectric layer 202 can be provided by a thin-film piezoelectric material provided by a zinc oxide (ZnO) film (or aluminium nitride, AIN, or lead zirconate fitanate, PZT) grown on a flexible substrate. The flexible substrate can be made from any suitable material as is known in the art, for example a polymer such as polyimide (PI), polyethylene terephthalate (PET) or polyethylene naphthalate (PEN), or provided by a metal foil/sheet such as aluminium.

In other examples, the piezoelectric layer 202 can be provided by a piezoelectric polymer such as polyvinylidene fluoride (Pk/DF) or its derivatives.

Positioned on the piezoelectric layer 202 is a metallic IDT (interdigital transducer) electrode 204. The piezoelectric layer 202 and IDT electrode 204 together form a SAW transducer 203. Although IDT electrodes are generally preferred, other electrode configurations are possible, for example coplanar electrodes or piezoelectric transducer (PZT) electrodes.

The IDT electrode 204 is connected to a first connection pad 205a and second connection pad 205b. This enables the IDT electrode 204to be electrically connected to the connecting lead 104 (not shown in Figure 2). The IDT electrode 204 can be deposited on the piezoelectric layer 202 using techniques known in the art. For simplicity, the SAW transducer 203 shown in Figure 2 only includes a single IDT electrode. However, as explained in more detail below, in other embodiments, the SAVVtransducer 203 may include more than one IDT electrode, specifically the SAW transducer 203 may comprise an array of IDT electrodes.

The piezoelectric layer 202 is positioned adjacent to an active substance-infused layer 207 which has infused therein a compound comprising an active substance.

The active substance-infused layer 207 typically comprises a suitable gel, such as a hydrogel. However, the active substance-infused layer 207 can be provided by any suitable material in which a suitable medicament can be infused (suspended or dissolved). Examples include lotions, creams, pastes, polymer structures or any other suitable amorphous or crystalline structured material.

Although not explicitly depicted in the simplified schematic drawing depicted in Figure 1, in certain embodiments, the active substance delivery patch 101 will be configured so that the active substance-infused layer 207 is removable and replaceable (for example by being in the form of a removable adhesive/suitably tacky sheet) allowing other elements of the active substance delivery patch 101, notably the piezoelectric layer 202 to be re-used.

The piezoelectric layer 202 is flexible which means, in combination with the inherent flexibility of the active substance-infused layer 207 the active substance delivery patch 101 is flexible and can thereby readily conform to the profile of the subject's body.

In use, the active substance delivery patch 101 is positioned on the skin of a subject with the active substance-infused layer 207 in direct contact with the subject's skin. The dressing layer 201 may be provided with an adhesive which contacts the subject's skin and holds the active substance delivery patch 101 tightly in place.

The energising signal generator unit 103 generates an energising signal which is transferred into the SAW transducer 203 via the connecting lead 104.

This energising signal energises the IDT electrode 204. This gives rise to a time-varying electric field in the vicinity of the IDT electrode 204 which, in turn, induces surface acoustic waves at the interface between the piezoelectric layer 202 and the active substance-infused layer 207. The acoustic energy associated with these surface acoustic waves is transmitted into the active substance-infused layer 207 and then onwards into the interface between the skin surface 301 and the active substance-infused layer 207 This transmission of acoustic energy causes the active substance initially suspended or dissolved in the active substance-infused layer 207 to pass into the subject's skin by virtue of a number of mechanisms which are described in more described below.

As will be described in more detail below, advantageously, structural and operational aspects of active substance delivery patch 101 arrangement described with reference to Figure 1 and Figure 2 can be optimised for the delivery of active substance of particular drugs or other treatments, and particular therapies. These parameters include the physical parameters of the patch such as the geometry and other physical properties of the SAW transducer 203 and the operational parameters of the energising signal generator unit 103.

The mechanisms by which the active substance pass into the subject's skin are described in more detail with reference to Figure 3.

Figure 3 provides a simplified schematic diagram depicting a cross-sectional view of the active substance delivery patch 101, in situ positioned on the skin surface 301 of a subject. Figure 3 shows in particular the dressing layer 201, piezoelectric layer 202, the IDT electrode 204 of the SAWtransducer 203, and the active substance-infused layer 207. Components relating to the energising signal generator unit and the connection to the energising signal generator unit are omitted for clarity.

The acoustic energy transferred to the interface between the skin surface 301 and the active substance-infused layer 207 temporarily disrupts the epidermal impervious layer of the subject's skin creating a plurality of permeable micropores. This is by virtue of acoustic energy agitating the lipid-protein layers of the top layers of the skin, temporarily reversibly separating them, and thereby forming micropores between the layers. Molecules of the active substance diffuse into the subject's body through these micropores.

The extent of this diffusion is increased because the active substance molecules are energised in micro bubbles by the acoustic energy as it passes through the active substance-infused layer 207.

The extent of the diffusion of the energised molecules into the skin is increased yet further by an increase in thermal energy (heating) in the piezoelectric layer 202 which in turn locally heats the active substance-infused layer 207 and thus the skin surface 301 below. In synergy with surface acoustic wave energising of molecules, the heating of the skin surface 301, even if only by a relatively low amount (for example to 40°C) increases the degree of diffusion, by well-defined diffusion dynamics, but also by reducing viscosity of protein-lipid substances between and around cells of the skin layers.

The extent of the diffusion of the energised molecules into the skin may be enhanced further still by virtue of the "internal streaming" effect known to be induced by surface acoustic waves. Such internal streaming may be induced in the active substance-infused layer 207 which increases the local pressure which in turn enhances the local transport of active substance molecules to the interface with the skin surface and then enhances the diffusion of the active substance molecules into the skin.

Additionally, by virtue of the structure of the active substance delivery patch 101, in particular, the positioning of the IDT electrode 204 of the SAW transducer 203 relative to the active substance-infused layer 207, the acoustic energy generated by the SAW transducer 203 drives the active substance molecules into the subject's skin.

Specifically, the surface acoustic waves generated by the SAW transducer 203 are Rayleigh waves (although other wave modes are possible) with both horizontal components (which propagate generally in a direction parallel to the skin surface 301) and vertical components (which propagate generally downwards in a direction perpendicular to the skin surface 301). Both these horizontal and vertical components give rise to the epidermal disruption; the energising of the active substance molecules, and thermal heating, all of which are described above. However, advantageously, because the IDT electrode 204 of the SAW transducer 203, is positioned directly over (above) the active substance-infused layer 207, vertical components of the acoustic energy generated by the SAW transducer 203 act to drive the active substance molecules into the skin, particularly in the region 302 of the skin surface 301 directly below the IDT electrode 204. This enhances further still the degree to which active substance molecules pass into the subject's body through the skin surface 301.

This combination of mechanisms, and in particular the vertical components of the surface acoustic waves driving the molecules into the subject's body mean that active substance molecules with molecule sizes and solubility properties that would otherwise inhibit or prevent transdermal absorption can administered by transdermal patches arranged in accordance with embodiments of the invention.

As mentioned above, in certain embodiments, the active substance delivery patch is flexible which means it can readily conform to the shape of the body of the subject on whom it is applied. This is particularly useful if the profile of the skin surface changes due to the subject moving. Further, in such embodiments, the fact that the active substance delivery patch conforms more closely to the shape of the subject's body means that the degree of skin heating and disruption of the epidermal impervious layer is increased, compared, for example to the case where the active substance delivery patch was rigid (i.e., not flexible, or minimally flexible).

Figure 4 provides a simplified schematic diagram depicting components of the energising signal generator unit 103.

As can be seen from Figure 4, the energising signal generator unit 103 comprises a data processor 401 connected to a control input/output interface 402, a memory unit 403 and a signal generator 404 and an amplifier 405. An output of the amplifier 405 is connected to the connecting lead 104.

The memory unit 403 has stored on thereon one or more control protocols 406. The components of the energising signal generator unit 103 are powered by a power supply 407. The power supply 407 can be provided by any suitable means but is typically provided by a suitable battery. However, in certain embodiments, particularly where the energising signal generator unit 103 is integrated with the active substance delivery patch 101, the power supply 407 can be provided by an energy harvesting power supply that converts mechanical movement to which the power supply 407 is subject (for example when the subject moves around) into energy and stores this energy.

The control protocols 406 stored in the memory unit 403 each relate to a particular treatment and/or a particular treatment therapy. The protocols may specify a particular length of time over which the SAW transducer 203 is to be energised to deliver a particular therapy and/or may specify the parameters of a transducer energising signal, for example, its amplitude, frequency and/or other characteristics of its waveform.

The energising signal generator unit 103 can be arranged to control the administering of active substances in any suitable way. In certain examples, the energising signal generator unit 103 can control the administration of a single, "one-off" dose, in other examples a pattern of doses can be administered (for example, a dose delivered at a regular interval (for example, once every 6 hours, or any other suitable pattern of drug administration). In other examples, active substances can be delivered continuously. That is, the SAW transducer can be continuously energised to deliver an active substance continuously. This could occur, for a set amount of time or until, for example, the active substance-infused layer was exhausted of active substance to administer.

The control input/output interface 402 can be configured in any suitable way. In some examples it can be provided by a physical control interface including, for example a display screen and control buttons, enabling it to be directly controlled by an operative or by the subject on whom the active substance delivery patch 101 is secured.

In other examples, the output interface 402 can be provided by a communication unit such as a short-range radio transceiver enabling the energising signal generator unit 103 to receive control instructions from another device, for example a nearby smartphone, or similar device, via a Bluetooth protocol radio link. In this way, the energising signal generator unit 103 can be wirelessly controlled and thus remotely controlled. In certain embodiments, the energising signal generator unit is integrated with the active substance delivery patch as a single unit. Advantageously, in such embodiments, the active substance delivery patch itself can be wirelessly controlled and thus remotely controlled.

In use, the output interface 402 receives control input for controlling operation of the energising signal generator unit 103. The output interface 402 generates a corresponding control signal which is communicated to the data processor 401. Responsive to receipt of this control signal, the data processor 401 loads an appropriate control protocol from the control protocols 406 stored in the memory unit 403. The data processor 401 then runs this control protocol and generates corresponding control signals for controlling the signal generator 404 to generate transducer energising signals in accordance with the control protocol. The signal generator/amplifier then generates these transducer energising signals which are transmitted to the SAWtransducer 203 of the active substance delivery patch 101 via the connecting lead 104.

In the example shown in Figure 1, the SAW transducer203 comprises a single IDT electrode. However, in other embodiments, a greater number of IDT electrodes may be provided, for example 2, 3, 4, 6, 12 or any other suitable number.

The IDT electrode shown in Figure 1 is generally circular in configuration. Figure 5 provides a more detailed view of such a circular electrode configuration.

Other electrode configurations can be used. for example, a "linear", substantially rectangular electrode configuration as depicted generally in Figure 6 can be used.

However, advantageously, circular electrode configurations tend to focus the acoustic energy in a given region of the thin-film piezoelectric layer. Further circular electrode configurations tend to increase the minor vertical components of the acoustic energy which enhances the degree to which molecules of the active substance are driven through the disrupted impervious epidermis. This means that circular electrode configurations can be used to increase the amount of active substance delivered in a particular region of the patch. This can be used as a dosage control: multiple patches can be provided, each with a different number of circular IDT electrodes in the SAWtransducer enabling a specific patch to be selected depending on the dosage requirement.

Alternatively, control circuitry at the energising signal generator unit 103 in combination with a suitable connecting lead can be used to selectively change the number of circular IDT electrodes in a patch that are energised, thereby enabling dosage control.

Further still, with appropriate alignment, the delivery of an active substance can be concentrated on a specific region of the skin by aligning a specific circular electrode, or group of circular electrodes, over the specific region of skin.

As mentioned above parameters of the patch can be optimised for particular active substances and particular therapies.

Active substance molecules of different drug compounds vary in size, shape, molecule weight, solubility, and other properties. Consequently, there is a variance in the kinetic response of different active substance molecules to SAW-induced acoustic energy, in particular in the degree to which the active substance molecules are driven into the subject's body and then diffuse in the subdermal layers.

Consequently, the optimal penetration and diffusion of different drug compounds will typically require different applications of acoustic energy, for example different frequencies, amplitudes, distribution of energy intensifies, duty cycles and so on.

Advantageously, because the geometry and design of SAWtransducers are highly adaptable and easily customisable, different SAWtransducer geometries and designs can be readily empirically investigated to determine which arrangements provide optimal drug delivery for different drug compounds.

If made from gel, properties of the gel of the active substance-infused layer, for example the gel's depth, viscosity and the partition coefficient between the gel and a subject's skin can similarly be empirically investigated and adapted accordingly.

Similarly, properties of the energising signal provided by the energising signal generator unit (for example, as defined in the control protocols) can be empirically optimised for different drug compounds and for different drug therapies. These properties include, but are not limited to, amplitude, frequency, waveform, duty cycle, duration, or total energy imparted. Specific active substances may be optimally transferred by an optimum value of any one or any combination of these properties where values less than, or more than, the optimum value or values, result in less optimum amounts of drug compound being transferred to the subject.

In certain embodiments, structural properties of the transdermal patch can be modified to induce turbulence in the surface acoustic waves and the resulting distortion acts to redirect horizontal components to vertical components and thereby enhance the degree to which energised active substance molecules are driven into the subject's body and also enhance the disruption to the epidermal impervious layer.

These structural modifications include introducing non-homogeneous (non-uniform) density in, for example the piezoelectric layer and/or the active substance-infused layer. In other words, providing regions of higher density and regions of lower density. In certain examples, this can be achieved by the introduction of physical apertures/orifices (air gaps) in the piezoelectric layer and/or the active substance-infused layer.

In other examples, the active substance-infused layer may comprise a hydrogel with a structure that varies so that regions of the hydrogel retain a greater amount of liquid than other regions. Alternatively, or additionally, the active substance-infused layer may have suspended therein a molecule matrix of varying density.

Figure 7 provides a simplified schematic diagram depicting a SAWtransducer 701 comprising a plurality of IDT electrodes 702 positioned on a piezoelectric layer 703.

As can be seen from Figure 7, evenly distributed across the piezoelectric layer 703 are a plurality of shaped strain-relieving apertures 705 extending the entire depth of the piezoelectric layer 703.

As mentioned above, in certain embodiments, active substance delivery patches in accordance with embodiments of the invention are flexible which means that they can readily conform to the shape of a subject's body. However, the resultant flexing of the piezoelectric layer could impart mechanical strain on the IDT electrodes 702 which may damage them. As will be understood, by introducing the shaped strain-relieving apertures 705 as shown in Figure 7, surface flex will be focused on the regions of the shaped strain-relieving apertures 705 and consequently be reduced in the region of each IDT electrode 702 thereby reducing the likelihood of flexing of the piezoelectric layer damaging the electrodes.

As can be seen from Figure 7, each shaped strain-relieving aperture 705 is substantially cross-shaped with a first opening extending along a first axis ('X'-axis) of the piezoelectric layer 703 centrally intersecting a second opening extending along a second axis ('Y'-axis), orthogonal to the first axis. Advantageously, this means that each shaped strain-relieving aperture 705 will act as a focus for surface flex along both "X" and "Y" axis of the piezoelectric layer 703.

In the simplified example described with reference to Figure 1, the active substance delivery patch 101 comprises a piezoelectric layer 202 which is positioned over the active substance-infused layer 207. However, in certain embodiments, further layers may be provided. For example, a further flexible layer made from PET may be positioned over the thin-film piezoelectric layer. Such a further layer may protect the thin-film piezoelectric layer. Such an arrangement is depicted generally in Figure 8. Figure 8 provides a simplified schematic diagram depicting an exploded view of an active substance delivery patch 801 including a dressing layer 802 and piezoelectric layer 803 on which is positioned a SAW transducer 804, where the SAW transducer 804 is positioned over an active substance-infused layer 805. However, as can be seen from Figure 8, positioned over the piezoelectric layer 803 (i.e., between the piezoelectric layer 803 and the dressing layer 802) is a further protective flexible layer 806.

Figure 9 provides a simplified schematic diagram depicting an exploded view of an active substance delivery patch 901 in accordance with a further embodiment. The active substance delivery patch 901 corresponds with the active substance delivery patch 801 shown in Figure 8 except that the further protective flexible layer 806 is omitted (although this layer can be included in certain embodiments) and it includes a further intermediate layer 902. The further intermediate layer 902 is positioned between the substance-infused layer 805 and the piezoelectric layer 803. The further intermediate layer 902 may be made from a similar material to the substance-infused layer 805, for example a hydrogel, and have diffused therein particles of a suitable compound.

In this embodiment, rather than the molecules of the substance-infused layer 805 being energised directly by acoustic energy from the SAW transducer 804, particles in the further intermediate layer 902 are energised, and these energised particles then energise the molecules of the substance-infused layer 805. The compound diffused in the further intermediate layer 902 can be selected so that its particles when energised, optimally energise the molecules of the substance-infused layer 805.

This arrangement has the further advantage of isolating the substance-infused layer 805 from the piezoelectric layer 803 which may be advantageous in enhancing the stability of the active substance infused in the substance-infused layer 805, for example during storage.

In Figure 1, the energising signal generator unit 103 is shown as a separate component from the active substance delivery patch 101, however as mentioned above in other embodiments, the energising signal generator unit and the active substance delivery patch may be integrated as a single unit.

In certain applications, it may be particularly important to ensure that the temperature of the active substance delivery patch remains regulated, for example, to ensure that the active substance-infused layer does not exceed a predetermined temperature. Accordingly, in certain examples, the energising signal generator unit is configured to thermally regulate the temperature of the active substance delivery patch by periodically activating it, rather than continuously activating it.

In examples in which the energising signal generator unit is incorporated with the active substance delivery patch as a single unit, the energising signal generator unit may include a temperature sensor for detecting, and thereby regulating the temperature of the active substance delivery patch. Alternatively (or additionally), the energising signal generator unit may be configured to ensure that for a given active substance delivery patch arrangement (taking into account the structure of the SAW transducer and the active substance-infused layer, for example), the amount of power transferred to the SAW transducer is such that the active substance delivery patch does not exceed a predetermined temperature.

Further, in the example shown in Figure 1, the energising signal that energises the SAW transducer 203 is conveyed from the energising signal generator unit 103 to the active substance delivery patch 101 via a physical wired connection (i.e., via the connecting lead 104). However, in alternative embodiments, the SAW transducer can be energised wirelessly. For example, the energising signal generator unit and the active substance delivery patch can each be provided with a transceiver antenna which replaces the connecting lead. The energising signal generator unit transmits an energising wireless signal from its transceiver antenna which intersects the transceiver antenna of the active substance delivery patch which then generates an energising current which energises the IDT electrodes of the SAW transducer.

Figure 10 provides a simplified schematic diagram depicting a piezoelectric layer 1001 of such an embodiment in which a single IDT electrode 1002 forming a SAW transducer is coupled to a peripheral antenna energy receiving antenna 1003 which is deposited on the piezoelectric layer 1001 and configured to receive wireless energising signals for energising the SAW transducer.

In the examples described above, the active substance delivery patch comprises a single SAW transducer which may be provided with a single IDT electrode or multiple IDT electrodes patterned onto a single substrate.

However, in other embodiments, the active substance delivery patch can comprise multiple SAW transducers, e.g., multiple independent substrates, each with one or more IDT electrodes. In this way, in certain embodiments, the active substance delivery patch may comprise an array of SAWtransducers with, for example, each transducer capable of being operated independently. This allows for increased sensitivity, improved spatial resolution, and other benefits, depending on the specific application.

In the embodiments described above, the active substance infused layer is typically provided by a suitable material such as a hydrogel in which is infused the active substance. In such embodiments, the geometry of this layer is typically of a substantially planar (albeit typically flexible) form.

However, in certain examples, the active substance infused layer may take other forms. For example, the active substance-infused layer may incorporate shaped microneedles fabricated from active substance incorporated materials which serve as a controlled-release substrate for the active substance when subjected to surface acoustic waves.

Typically, the geometry of the shaped microneedles will be chosen to amplify/concentrate acoustic energy from the SAW transducer such that the needles refine, optimise, and sustain delivery of the active substance into and through the stratum corneum and into sub dermal layers of the skin.

Advantageously, such an arrangement can be optimised to limit pain by ensuring minimal and controlled 'pressure-free' penetration of microneedles into the nerve-layers of the sub-epidermis, or by ensuring controlled and minimised physical effects on the nerves.

In operation, an active substance delivery patch comprising an active substance-infused layer incorporating shaped microneedles can be applied to the skin with minimal pressure. The acoustic energy from the SAW transducer provides controlled penetration of the microneedles (particularly to a controlled depth) through the epidermis, and concurrent release and delivery of molecules powered by the acoustic energy.

In some instances, the microneedle will be fabricated from bioresorbable materials like polycaprolactone, or poly lactic acid, or other materials, to optimise delivery of the active substance, and such that if they remain after treatment, they are resorbed.

All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. Each feature disclosed in this specification (including any accompanying claims, abstract and drawings) may be replaced by alternative features serving the same, equivalent, or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features. The invention is not restricted to the details of the foregoing embodiment(s). The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity.

It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims are generally intended as "open terms (e.g., the term "including" should be interpreted as "including but not limited to," the term "having" should be interpreted as "having at least," the term "includes" should be interpreted as "includes but is not limited to," etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases "at least one" and "one or more" to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles "a" or "an" limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases "one or more" or "at least one" and indefinite articles such as "a" or "an" (e.g., "a" and/or "an" should be interpreted to mean "at least one" or "one or more"); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (e.g., the bare recitation of "two recitations," without other modifiers, means at least two recitations, or two or more recitations).

It will be appreciated that various embodiments of the present disclosure have been described herein for purposes of illustration, and that various modifications may be made without departing from the scope of the present disclosure. Accordingly, the various embodiments disclosed herein are not intended to be limiting, with the true scope being indicated by the following claims.

Claims

CLAIMS1. A patch for the transdermal delivery of an active substance, said patch comprising: at least one surface acoustic wave transducer comprising one or more electrodes positioned on a piezoelectric layer, and an active substance-infused layer positioned adjacent the piezoelectric layer. wherein the at least one surface acoustic wave transducer is located relative to the active substance-infused layer such that the one or more electrodes are positioned over the active substance-infused layer, such that in use when the patch is positioned on a subject's skin and when the at least one surface acoustic wave transducer is energised: acoustic energy generated by the at least one surface acoustic wave transducer gives rise to a transfer of active substance molecules infused in the active substance-infused layer into the subject's body through the subject's skin.
A patch according to claim 1, wherein the one or more electrodes are interdigitated electrodes.
3. A patch according to claim 2, wherein the one or more interdigitated electrodes have a circular configuration.
4 A patch according to any previous claim, further comprising an energy receiving antenna coupled to the at least one surface acoustic wave transducer, wherein the at least one surface acoustic wave transducer is configured to be wirelessly energised by energy received by the energy receiving antenna.
5. A patch according to any previous claim, wherein the piezoelectric layer is flexible such that the transdermal patch is able to conform to a profile of the subject's body in use.
6. A patch according to claim 5, wherein the piezoelectric layer comprises one or more strain-relieving apertures configured to reduce strain to which the at least one surface acoustic wave transducer is subject when the transdermal patch is subject to flexing.
7. A patch according to claim 5 or claim 6, comprising a further flexible layer positioned relative to the piezoelectric layer for protecting the piezoelectric layer and the at least one surface acoustic wave transducer.
8. A patch according to any previous claim, wherein the active substance-infused layer is removable and replaceable.
9. A patch according to any previous claim, wherein regions of the piezoelectric layer and/or active substance-infused layer are of non-uniform density to redirect horizontal components of the acoustic energy generated by the at least one surface acoustic wave transducer in a vertical direction towards the subject's skin when in use.
10. A drug delivery system comprising a patch according to any previous claim and an energising signal generator unit connectable to the transdermal patch and configured to generate an energising signal for energising the at least one surface acoustic wave transducer of the active substance delivery patch.
11. A drug delivery system according to claim 10, wherein the energising signal generator unit comprises an energy harvesting power supply.
12. A drug delivery system according to claim 10 or 11, wherein the transdermal patch and the energising signal generator unit are integrated as a single unit.