<p>TITLE</p>
<p>Transdermal drug delivery device with latch</p>
<p>DESCRIPTION</p>
<p>Technical field</p>
<p>The invention relates to the transdermal administration of drugs to a patient without the use of a syringe. The term "drug" is used to refer to any biologically active substance that needs to be delivered into the bloodstream of the patient, whether therapeutic or not, for example pharmaceuticals, vaccines and proteins. The patient may be human or animal.</p>
<p>Background</p>
<p>The history and advantages of transdermal drug delivery systems are set out in patent application GB 2414675 A. That patent application describes a transdermal drug delivery device that adheres to the skin of a patient and comprises a reservoir layer containing a drug to be administered to the patient. The lower surface of the reservoir layer (i.e. the surface closest to the skin of the patient in use) is formed by a resilient membrane perforated by pores. An extensor layer, which is preferably formed by microelectromechanical (MEMS) techniques, stretches and compresses the reservoir layer to open and close the pores in the resilient membrane and allow or inhibit the delivery of the drug through the pores to the patient. When the extensor layer is stretched, the skin of the patient to which the device is adhered is also stretched, which may enhance delivery of the drug through the skin by opening the pores and follicles in the skin, and/or by disruption of the dead protein cells and lipid bi-layers in the stratum corneum.</p>
<p>GB 2414675 A gives as examples of frequencies at which the device may be actuated a range from 1000 cycles per second to one cycle per 300 seconds. The high frequency end of the range is most suitable for high viscosity drugs and principally uses mechanical pressure from the device to force the drug through the disrupted stratum corneum of the patient's skin. The low frequency end of the range is most suitable for low viscosity drugs and principally allows the drug to diffuse through the opened pores in the patient's skin while the pores in the resilient membrane of the device are held open for an extended time.</p>
<p>It has been found that operating the device at low frequency requires a large expenditure of energy because the MEMS component must operate continuously to keep the membrane stretched for an extended period, using power all the time. As a result, either the lifetime of the battery that supplies power to the device is unacceptably short, or a larger battery must be used thereby adding to the cost of the device and restricting miniaturization of it, which is desirable to aid patient comfort.</p>
<p>The invention The invention provides a transdermal drug delivery device as defined in claim 1.</p>
<p>Preferred but not essential features of the device are defined in the dependent claims.</p>
<p>The use of a latch allows the apertures to be held in their non-relaxed state without the need for continuous power to the electromechanical actuator, thereby solving the problem of energy loss in the prior art. Power is only required to move the apertures between the two states and is not required to hold them in either state. The non-relaxed state may be either the state with open apertures or the state with closed 2fl rntrfiir'c The drawing Figure 1 is an exploded view showing the general structure of a transdermal drug delivery device according to a preferred embodiment of the invention.</p>
<p>Detailed description of the invention</p>
<p>The transdermal drug delivery device illustrated in Figure 1 comprises a reservoir layer 10 that includes a series of chambers containing one or more drugs in one or more type of formulation. The reservoir layer 10 is flexible and its lower surface is bounded by a resilient membrane 12, which is perforated by pores through which the drug formulation can pass. An adhesive layer 14 is applied to the membrane 12, which is intended to attach the device to the skin of a patient. The adhesive layer 14 must be suitable for removably bonding the membrane 12 to human or animal skin.</p>
<p>A second adhesive layer 16, which may comprise a different adhesive from the layer 14, bonds an upper surface of the reservoir layer 10 to an extensor layer 1 8. In this embodiment of the invention, the extensor layer 18 is formed as a rnicroelectromechajical (MEMS) device. A third layer of adhesive 20, which may be similar to the second layer 16, bonds the extensor layer to a control layer 22 comprising microelectronic control circuitry for the extensor layer 1 8. A battery (not shown) or other power source for the device may be provided in the control layer 22 or elsewhere. Electrical contacts between the extensor layer 1 8 and the control layer 22 are indicated schematically by dotted lines 23.</p>
<p>The device operates by control layer 22 controlling the extensor layer 18 to alternately extend and relax the reservoir layer 10, so that the drug is squeezed out of the chambers in the reservoir layer 1 0 and through the pores in the resilient membrane 1 2.</p>
<p>The stretching and relaxation of the reservoir layer 10 leads to stretching and elongation and relaxation of the pores 26 in the base of the reservoir layer 10. The 21) forre on the contents of the reservoir leads to the contents being phyica11y forced in the direction of the skin surface and its appendages.</p>
<p>The stretching and relaxation of the reservoir layer 10 leads in turn to stretching and relaxation of the adhesive layer 14 at the base of the reservoir layer 10 that is attached to the skin. This consequently leads to stretching and relaxation of the skin and its surface layer, the stratum corneum, and pores such as sweat pores and hair follicles.</p>
<p>Extension and relaxation of the skin surface results in disruption of the skin surface cells/barrier and enlargement of pore diameters of the appendages, thus enhancing the delivery of the drug or therapeutic agent through the skin into the body.</p>
<p>The foregoing description of Figure 1 is common to the prior art shown in GB 2414675 A and to certain preferred embodiments of the present invention. The present invention is characterized by a latch (not illustrated) that holds the apertures in either their open state or their closed state without continued operation of the electromechanical actuator.</p>
<p>In a first embodiment of the present invention, the apertures are pores in a resilient membrane, which are formed so as to he closed when the membrane is in its relaxed state. The actuator is a MEMS device that operates to extend the membrane and open the pores to allow the drug to flow through them. When the membrane has been extended so that the pores are fully open, the latch can be operated to hold the membrane in that state for an unlimited period, during which the actuator may he switched off.</p>
<p>If the desired drug delivery regime requires that the supply of drug should be cut off after a predetermined time, the latch can be released when that time has elapsed. The latch may be released by the same actuator or by a second actuator. Normally, the natural resilience of the membrane is then sufficient to return the membrane to its relaxed state and re-close the apertures. Alternatively, the actuator may actively drive the apertures closed. Such a cycle may be repeated as often as necessary, in accordance with a predetermined drug delivery regime. In some instances the physical properties of the drug and the capacity of thc chambcrs may be such that after the predetermined time effectively all of the drug has been delivered to the patient. In such instances, there may be no need to re-close the apertures and therefore no need to provide a mechanism for releasing the latch.</p>
<p>In a second embodiment of the invention, the apertures are again pores in a resilient membrane but they are formed so as to be open when the membrane is in its relaxed slate. During manufacture of the device, after the chambers have been filled, the resilient membrane is compressed to close the pores and seal the drug in the chambers. When the membrane has been compressed so that the pores are fully closed, the latch can be operated to hold the membrane in that state for an unlimited period, during which the actuator may be switched off The pores remain latched closed during transport and storage of the device and until it is ready to be used.</p>
<p>When delivery of the drug to a patient is to begin, the MEMS actuator may operate to release the latch, whereupon the natural resilience of the membrane will usually he sufficient to return the membrane to its relaxed state and open the apertures.</p>
<p>Alternatively, a second actuator may drive the apertures open.</p>
<p>If the prescribed drug delivery regime requires that delivery of the drug should be cut off after a predetermined time, the second actuator may operate against the resilience of the membrane to drive the apertures closed again and the latch may then be engaged to hold them in that state without further expenditure of energy. The cycle can be repeated as necessary, in accordance with the prescribed drug delivery regime.</p>
<p>In some instances the physical properties of the drug and the capacity of the chambers may he such that after the predetermined time effectively all of the drug has been delivered to the patient. In such instances, there may be no need to re-close the apertures and therefore no need to provide a second actuator to drive them closed.</p>
<p>In further embodiments, the apertures need not be part of a resilient membrane hut can he resilient tubes or rigid channels leading from the chambers towards the skin of the patient. Resilient tubes may be closed by the actuator pinching them to constrict their cross-section. Both tubes and channels may be closed by the actuator 7fl ohsructing them with a cap or with a valve member. If the apertures arc not formed so as to he naturally resilient, the actuator may incorporate a spring to bias it towards one state of the apertures, or the actuator may drive the device in both directions between the two states as described above.</p>
<p>The latch is preferably a mechanical latch, which holds the apertures in the desired state by physical engagement between two solid parts of the device, and in particular by engagement between a fixed part and a moving part of the actuator. One part may hook over or interlock with the other part; or one part may be held frictionally between jaws of the other part. Alternatively or additionally, the latch may use magnetic or electrostatic means to hold the apertures in the desired state without expenditure of power.</p>
<p>For more positive control of the state of the device, it is possible to provide two latches so that the apertures can be positively held in each of the two states.</p>
<p>Because the transdermal delivery device of the invention allows the apertures to he held open without expenditure of energy, they may remain open permanently or for an indefinitely long time: from fractions of seconds up to minutes, hours or days. This allows the device to administer drug delivery regimes that were not available to prior devices.</p>
<p>In one embodiment, the device may incorporate multiple, discrete chambers, each of the chambers having its own, independently controllable actuator. The respective actuators may be controlled to open the chambers at overlapping or successive times.</p>
<p>Purely by way of example, seven successive chambers may be opened at the same time each day over a course of treatment lasting one week. This is likely to provide a more consistent dose than repeatedly opening a single chamber.</p>
<p>If necessary, in such a regime chambers that have been opened previously may he re-closed either before or at the same time as succeeding chambers are opened. In the latter case, it may be possible to arrange that operation of the actuator appropriate for opening one chamber aho releases the latch to CIOSC thc previous chaibe1. Tue chambers may contain di iferent drugs, all the same drug, or different formulations or doses of the same drug, as determined by the prescribed regime.</p>
<p>Given that the device of the present invention is intended to hold the apertures open for relatively long periods of time, and to deliver the drug slowly to the patient over those long periods, it may not be necessary or beneficial for the device to stretch the patient's skin to promote delivery of the drug through the skin barrier. If the device is designed so that operation of the actuator does not result in stretching of the skin, this may aid the adhesive layer to remain bonded with the skin and reduce the risk that the device becomes detached during use.</p>