Patent Publication Number: US-2013237959-A1

Title: Method and a delivery device for administering an active substance to a subject

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a Continuation of U.S. application Ser. No. 12/744,786, filed May 26, 2010, which is a 371 of PCT/IE2008/000115 filed Nov. 28, 2008, which claims priority from Ireland Application No. S2007/0861 filed Nov. 28, 2007, and from Ireland Application No. S2008/0884 filed Nov. 4, 2008, the disclosures of each which are incorporated by reference. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates to a delivery device for administering an active substance to a subject, and the invention also relates to an injectable element for administration to a subject. The invention further relates to a method for administering an active substance to a subject. 
     BACKGROUND OF THE INVENTION 
     Delivery devices for delivering an active substance to a subject are known. One type of delivery device which is currently gaining acceptance is commonly referred to as a micro-delivery device. Such micro-delivery devices are particularly suitable for delivering an active substance transdermally, transcutaneously and intradermally, and comprise a laminated structure, which typically comprises three or four layers which are separated by respective membranes. A first layer which is located between a second layer and a third layer is provided with a plurality of first chambers for storing the active substance to be administered transdermally to the subject. The first chambers typically are formed by bores extending through the first layer and are arranged in a matrix in the first layer and sealed by respective first and second membranes located at respective opposite major surfaces of the first layer. 
     The second layer typically comprises a plurality of second chambers formed by bores extending through the second layer and arranged in a matrix and aligned with the corresponding first chambers. The first membrane is located between the first and second layers for sealably isolating the first and second chambers from each other. A driving medium is located in each of the second chambers for urging the first membrane into the first chambers for discharging the active substance from the corresponding first chambers. Typically, the driving medium comprises an expandable medium which expands in response to an increase in temperature. 
     The third layer is located on the opposite side of the first layer to that of the second layer and comprises a plurality of micro-needles extending therefrom for penetrating the skin of a subject. A bore extends through each micro-needle for accommodating the active substance therethrough from the corresponding first chamber. The second membrane is located between the first layer and the third layer, which sealably isolates the first chambers from the bores of the respective micro-needles. The second membrane is of a burstable material which bursts in response to an increase in pressure in the first chambers resulting from expansion of the first membrane into the first chambers for in turn communicating the first chambers with the bores through the corresponding micro-needles for delivering the active substance transdermally to the subject. 
     In such micro-delivery devices a fourth layer is provided which comprises a plurality of heating elements which are formed on the fourth layer for raising the temperature of the driving medium. The fourth layer with the heating elements thereon may be secured directly to the third layer, or secured to the third layer through a third membrane which sealably isolates the second chambers from the corresponding heating elements. By appropriately activating the heating elements to raise the temperature of the driving medium, the driving medium expands, thereby urging the first membrane into the first chambers and raising the pressure of the active substance in the first chambers. The rise in pressure in the first chambers results in the second membrane bursting at locations adjacent the first chambers, thereby communicating the first chambers with the bores in the corresponding micro-needles. The action of the first membrane on the active substance urges the active substance from the first chambers through the bores in the micro-needles, and in turn transdermally into the subject. 
     Typically the heating elements are activatable individually sequentially or in groups sequentially for delivering the active substance to the subject in specific doses to comply with a predefined treatment regime. Such a treatment regime may require a dose of the active substance to be administered to the subject three times per day during a treatment period, which could be a period of five days or more. This requires the micro-delivery device to be attached to the subject for the duration of the treatment period with the micro-needles continuously penetrating the skin of the subject. This is undesirable, since it can lead to irritation and infection of the skin, which leads to and in many cases considerable discomfort. 
     There is therefore a need for a delivery device for administering an active substance to a subject which addresses this problem. 
     The present invention is directed towards providing such a delivery device and the invention is also directed to a method for administering an active substance to a subject, and the invention is also directed towards providing an injectable element for administering an active substance to a subject. 
     SUMMARY OF THE INVENTION 
     According to the invention there is provided a delivery device for administering an active substance to a subject, the device comprising a plurality of first chambers, a solid form structure located in each first chamber, the solid form structure having a pointed tip and comprising the active substance, and an urging means for urging the solid form structures through the first chambers to penetrate the skin of the subject with the pointed tips thereof. 
     In one embodiment of the invention each solid form structure comprises a support material for supporting the active substance therein. 
     Preferably, the support material of each solid form structure is configured as a scaffolding structure, and the active substance is in solid form supported by the scaffolding structure. Advantageously, the scaffolding structure is of lattice construction. 
     In another embodiment of the invention the support material of each solid form structure is porous and the active substance is impregnated therein. 
     Alternatively, the active substance is coated onto the support material of each solid form structure. 
     In another embodiment of the invention the support material of each solid form structure is adapted for facilitating slow release of the active substance therefrom. 
     Preferably, the support material of each solid form structure comprises a biodegradable material. Advantageously, the support material of each solid form structure comprises a polymer material. 
     In another embodiment of the invention each solid form structure comprises a mixture comprising the active substance and an excipient. 
     In another embodiment of the invention each solid form structure is slideable in the corresponding first chamber for penetrating the skin of a subject. 
     In a still further embodiment of the invention each solid form structure is slideable in the corresponding first chamber from a position entirely within the first chamber to a position whereby at least a portion of the solid form structure extends outwardly of the first chamber for penetrating the skin of a subject. 
     In one embodiment of the invention each solid form structure is a sealable sliding fit within the corresponding first chamber, and the urging means acts directly on the solid form structure for urging the solid form structure through the first chamber. 
     Preferably, the maximum transverse cross-sectional dimension of each solid form structure lies in the range of 0.1 mm to 2 mm. Advantageously, the axial length of each solid form structure lies in the range of 0.1 mm to 2 mm. 
     Preferably, each solid form structure comprises a tapering portion terminating in the pointed tip. Advantageously, each solid form structure comprises a portion of constant transverse cross-section, the tapering portion thereof extending axially from the portion of constant transverse cross-section. Ideally, the tapering portion of each solid form structure is of conical shape. Preferably, each solid form structure is of circular transverse cross-section. 
     In one embodiment of the invention the first chambers are configured in a matrix. 
     Preferably, the maximum transverse cross-sectional dimension of each first chamber lies in the range of 0.1 mm to 2 mm. Advantageously, the axial length of each first chamber lies in the range of 0.1 mm to 2 mm. 
     In one embodiment of the invention a first housing is provided, and the first chambers are located in the first housing. Preferably, the first housing comprises a first plate member defining opposite first and second major surfaces, and each first chamber is formed by a corresponding first bore extending through the first plate member from the first major surface thereof to the second major surface. Preferably, the first plate member is of thickness in the range of 0.1 mm to 2 mm. Advantageously, each first bore is of circular transverse cross-section. 
     In one embodiment of the invention a second chamber is provided for housing the urging means. 
     In another embodiment of the invention a second housing is provided, and the second chamber is located in the second housing. Preferably, a plurality of second chambers are located in the second housing. Advantageously, one second chamber is provided corresponding to each first chamber, the second chambers being aligned with the respective corresponding first chambers. 
     Preferably, the maximum transverse cross-sectional dimension of each second chamber lies in the range of 0.1 mm to 2 mm. 
     In one embodiment of the invention the second housing comprises a second plate member having opposite first and second major surfaces, and each second chamber is formed by a corresponding second bore extending through the second plate member from the first major surface thereof to the second major surface. Preferably, the second plate member is of thickness in the range of 0.1 mm to 2.0 mm. Advantageously, each second bore is of circular transverse cross-section. 
     Advantageously, the second chambers are configured in a matrix. 
     In one embodiment of the invention a first membrane is located between the first and second chambers for sealably isolating each first chamber from the second chamber. Preferably, the first membrane comprises a material impermeable to the urging means. Advantageously, the first membrane comprises a material impermeable to the active substance. Ideally, the first membrane is deformable into each first chamber under the action of the urging means for urging the corresponding solid form structure through the first chamber. Preferably, the first membrane is of an expandable material. 
     In one embodiment of the invention at least one pair of interengageable complementary formations is provided for locating the first and second plate members relative to each other with each first chamber aligned with the corresponding second chamber, one of the interengageable complementary formations being located on the second major surface of the first plate member adjacent one of the first chambers, and the other of the pair of interengageable complementary formations being located on the first major surface of the second plate member, the respective interengageable complementary formations of the pair thereof being co-operable with each other for entrapping the first membrane therebetween. Preferably, the interengageable complementary formation of the pair thereof located on the first plate member extends around the corresponding one of the first chambers. Advantageously, the interengageable complementary formation of the pair thereof located on the first plate member extends completely around the corresponding one of the first chambers. Preferably, the interengageable complementary formation of the pair thereof located on the second plate member extends around the corresponding one of the second chambers. Advantageously, the interengageable complementary formation of the pair thereof located on the second plate member extends completely around the corresponding one of the second chambers. 
     In one embodiment of the invention one of the interengageable complementary formations of the pair thereof comprises a projection extending from the corresponding one of the first and second plate members. Preferably, the projection comprises an annular projection. Advantageously, the other of the interengageable complementary formations of the pair thereof comprises a recess extending into the corresponding one of the first and second plate members for engaging the projection extending from the other of the first and second plate members. Preferably, the recess is configured as an annular recess. 
     In one embodiment of the invention a plurality of pairs of interengageable complementary formations are provided, one of the pairs of interengageable complementary formations being provided corresponding to each first chamber. 
     In another embodiment of the invention one urging means is provided in each second chamber. 
     In another embodiment of the invention a second membrane is provided for sealably closing each first chamber adjacent the pointed tip of the corresponding solid form structure. Preferably, the second membrane is adapted to be penetrable by the pointed tip of each solid form structure. 
     In another embodiment of the invention at least one activating means is provided for activating the urging means to urge at least one of the solid form structures through the corresponding first chamber to penetrate the skin of a subject. Preferably, a plurality of activating means are provided, each activating means being provided for activating the urging means in a corresponding one of the second chambers. 
     Advantageously, the respective activating means are aligned with corresponding ones of the second chambers. Advantageously, the activating means are configured in the form of a matrix. 
     In one embodiment of the invention each activating means comprises a heating means. Preferably, each heating means comprises an electrically powered heating means. Advantageously, each heating means comprises a thin film resistor. 
     Preferably, the activating means are formed on a third plate member. 
     In one embodiment of the invention the third plate member comprises a material selected from one of silicon, ceramics, polyimide and FR4. 
     In another embodiment of the invention the third plate member comprises a flexible material. 
     In a further embodiment of the invention a third membrane is located between the activating means and the at least one second chamber for sealably closing the second chamber. 
     In a still further embodiment of the invention a plurality of openings are formed through the third membrane adjacent respective corresponding ones of the second chambers, and each opening is sealably closed by a corresponding heat conducting element for conducting heat to the urging means in the corresponding second chamber. Preferably, the third membrane comprises a heat insulating material. 
     In one embodiment of the invention each urging means comprises an expandable driving substance. 
     In another embodiment of the invention the driving substance is in the form of a liquid, the liquid being responsive to one of temperature change and chemical activation for converting from a liquid phase to a gaseous phase for urging the solid form structure through the first chamber. 
     In another embodiment of the invention the driving substance comprises a solid responsive to one of temperature change and chemical activation for transitioning directly from a solid phase to a gaseous phase for urging the solid form structure through the first chamber. Preferably, the driving substance comprises Azobisisobutylonitrile (AIBN). 
     In another embodiment of the invention the driving substance comprises a plurality of gas filled microspheres responsive to temperature change for expansion thereof for urging the solid form structure through the first chamber. Preferably, the driving substance comprises gas filled microspheres sold under the Trade Mark EXPANCEL. 
     In a further embodiment of the invention the driving substance comprises a porous material, the pores of which are gas filled. 
     In one embodiment of the invention the porous material is responsive to temperature change for expansion thereof. 
     In another embodiment of the invention the gas in the porous material is responsive to temperature change for expanding out of the porous material. 
     In a further embodiment of the invention the porous material of the driving substance comprises a porous polymer material. 
     In one embodiment of the invention a securing means is provided for securing the delivery device to a site on a subject. 
     The invention also provides an injectable element for administering an active substance to a subject, the injectable element comprising a solid form structure having a pointed tip for penetrating the skin of the subject and comprising the active substance. 
     Additionally, the invention provides a delivery device for administering an active substance to a subject in the form of a solid form structure, the device comprising a plurality of first chambers for accommodating respective ones of the solid form structures, and an urging means for urging the solid form structures through the corresponding first chambers to penetrate the skin of the subject. 
     The invention further provides a method for administering an active substance to a subject, the method comprising configuring the active substance as a solid form structure having a pointed tip, locating the solid form structure in a first chamber, attaching the first chamber to the subject adjacent a site at which the active substance is to be administered, and urging the solid form structure through the first chamber to penetrate the skin of the subject by the pointed tip thereof. 
     Preferably, the method further comprises providing a first housing, providing a plurality of the first chambers and locating the first chambers in the first housing, and locating one solid form structure in each first chamber. 
     The advantages of the invention are many. A particularly important advantage of the invention is that the skin of the subject is not continuously penetrated by a plurality of micro-needles, as has been the case with such devices known heretofore. Thus, the risk of irritation, infection and discomfort to the subject is minimised, and in most cases is eliminated. Since the active substance is delivered to the subject by urging the solid form structures into penetrating engagement with the skin of the subject, the skin of the subject is only penetrated by those solid form structures which are urged out of the first chambers. Thus, where the solid form structures are provided to be of a biodegradable material, the solid form structures dissolve into the skin of the subject, and once dissolved, no longer penetrate the skin to cause irritation, discomfort and possible infection. It is envisaged, in general, that each solid form structure would be of a material which would biodegrade substantially simultaneously as the last of the active substance in the solid form structure is being released into the subject. It is envisaged that the release rate of the active substance from each solid form structure and the dissolve rate of each solid form structure could be substantially matched, and would be such that the active substance would be released at a relatively constant rate over the period while the solid form structure is dissolving. 
     A further advantage of the invention is that the solid form structures containing the active substance are stored within the first chambers which are sealed by the first and second membranes, and accordingly, the solid form structures can be stored in sterile conditions. 
    
    
     
       BRIEF DESCRIPTION OF THE INVENTION 
       The invention will be more clearly understood from the following description of some preferred embodiments thereof, which are given by way of example only, with reference to the accompanying drawings which are not to scale, in which: 
         FIG. 1  is a perspective view of a delivery device according to the invention for administering an active substance to a subject, 
         FIG. 2  is an exploded perspective view of the delivery device of  FIG. 1 , 
         FIG. 3  is a perspective view of the delivery device of  FIG. 1  illustrated with portions of the device in a different position to that of  FIG. 1 , 
         FIG. 4  is a transverse cross-sectional side elevational view of the delivery device of  FIG. 1 , 
         FIG. 5  is a view similar to  FIG. 4  illustrating the delivery device of  FIG. 1  in use, 
         FIG. 6  is a perspective view of an injectable element also according to the invention for use in the delivery device of  FIG. 1 , 
         FIG. 7  is an enlarged transverse cross-sectional view of a detail of the delivery device of  FIG. 1 , 
         FIG. 8  is a perspective view of another detail of the delivery device of  FIG. 1 , 
         FIG. 9  is a top plan view of a detail of a portion of the delivery device of  FIG. 1 , 
         FIG. 10  is a transverse cross-sectional view of the detail of  FIG. 9  of the delivery device of  FIG. 1 , 
         FIG. 11  is a block representation of an electronic circuit of the delivery device of  FIG. 1 , 
         FIG. 12  is a perspective view similar to  FIG. 1  of a delivery device according to another embodiment of the invention for administering an active substance to a subject, 
         FIG. 13  is a transverse cross-sectional side elevational view similar to  FIG. 4  of the delivery device of  FIG. 12 , 
         FIG. 14  is a perspective view similar to  FIG. 1  of a delivery device according to another embodiment of the invention for administering an active substance to a subject, 
         FIG. 15  is a transverse cross-sectional side elevational view of a portion of the delivery device of  FIG. 14 , 
         FIG. 16  is a perspective view of another portion of the delivery device of  FIG. 14 , 
         FIG. 17  is a transverse cross-sectional view of a detail of the portion of  FIG. 16  of the delivery device of  FIG. 14 , 
         FIG. 18  is a perspective view of another portion of the delivery device of  FIG. 14 , 
         FIG. 19  is a transverse cross-sectional side elevational view of a detail of the portion of  FIG. 18  of the delivery device of  FIG. 14 , 
         FIG. 20  is a perspective view similar to  FIG. 1  of a delivery device according to a further embodiment of the invention for administering an active substance to a subject, 
         FIG. 21  is a transverse cross-sectional side elevational view of a portion of the delivery device of  FIG. 20 , 
         FIG. 22  is a perspective view of another portion of the delivery device of  FIG. 20 , 
         FIG. 23  is a transverse cross-sectional side elevational view of a detail of the portion of  FIG. 22  of the delivery device of  FIG. 20 , 
         FIG. 24  is a perspective view of another portion of the delivery device of  FIG. 20 , 
         FIG. 25  is a transverse cross-sectional side elevational view of a detail of the portion of  FIG. 24  of the delivery device of  FIG. 20 , 
         FIG. 26  is a transverse cross-sectional side elevational view similar to  FIG. 4  of a delivery device according to another embodiment of the invention, and 
         FIG. 27  is a perspective view of an injectable element also according to the invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Referring to the drawings and initially to  FIGS. 1 to 11 , there is illustrated a micro- dimensioned delivery device according to the invention, indicated generally by the reference numeral  1 , for administering an active substance transdermally to a subject. The active substance is provided as an injectable element which is also according to the invention and is provided in the form of a solid form structure indicated generally by the reference numeral  2 , which in this embodiment of the invention is formed by a scaffolding structure  3  of a biodegradable polymer material into which the active substance is impregnated. The scaffolding structure  3  is configured as a lattice structure of the biodegradable polymer material, which when impregnated with the active substance forms a substantially solid structure of circular transverse cross-section comprising a base portion  4  of constant transverse cross-section of diameter d, and a tapering portion  6  of conical shape extending axially from the base portion  4  and terminating in a pointed tip  5  for penetrating the skin of the subject. The lattice structure of the biodegradable material is constructed to facilitate slow release of the active substance. The active substance may be any medicament or other solution which it is desired to administer transdermally to a subject. 
     The device  1  is adapted for securing to the subject adjacent the site at which the active substance is to be administered to the subject, as will be described below. 
     The device  1  comprises a first housing provided by a first plate member  7  of a polymer material in which a plurality of first chambers  8  are formed for containing respective ones of the solid form structures  2  of the active substance. The first plate member  7  defines a first major surface  9  and an opposite second major surface  10 . The first chambers  8  are formed by respective bores of circular transverse cross-section extending through the first plate member  7  from the first major surface  9  to the second major surface  10 , and the diameter of the first chambers  8  and the diameter d of the base portion  4  of the solid form structures  2  are such that the base portion  4  of the solid form structures  2  are a sliding fit in the first chambers  8 . 
     A second housing provided by a second plate member  12  also of a polymer material and having a first major surface  14  and a second major surface  15  is provided with a plurality of second chambers  16  also arranged in a matrix, and aligned with the first chambers  8  of the first plate member  7 . The second chambers  16  are formed by respective second bores of circular transverse cross-section which extend through the second plate member  12  from the first major surface  14  to the second major surface  15 . Each second chamber  16  houses an urging means, which in this embodiment of the invention is provided by a temperature responsive expandable driving substance  18 , which is described below, for urging the solid form structures  2  through the corresponding first chambers  8  for penetrating the skin of the subject by the pointed tip  5 , for in turn delivering the active substance transdermally to the subject. 
     A first membrane  20  of an expandable material, which is impermeable to both the active substance and the driving substance  18 , is located between and sealably secured to the first plate member  7  and the second plate member  12  for sealably closing the adjacent ends of the first and second chambers  8  and  16  adjacent the second major surface  10  and the first major surface  14  of the first and second plate members  7  and  12 , respectively, and for isolating the second chambers  16  from the corresponding first chambers  8 . The expandability of the first membrane  20  is such as to permit expansion thereof into the first chambers  8  on expansion of the driving substance  18  in the corresponding second chambers  16 , for in turn urging the corresponding solid form structures  2  through the first chambers  8  to penetrate the skin of the subject. 
     A second membrane  22  is sealably secured to the first major surface  9  of the first plate member  7  for sealably closing the ends of the first chambers  8  adjacent the first major surface  9  of the first plate member  7  so that the solid form structures  2  are maintained in the first chambers  8  in a sterile environment. The second membrane  22  is of a penetrable material which is penetrable by the pointed tips  5  of the solid form structures  2  as the solid form structures  2  are being urged through the first chambers  8  for in turn penetrating the skin of the subject. 
     A third plate member  24  having a first major surface  25  and a second major surface  26  is secured to the second plate member  12  with a third membrane  27  located therebetween. The third plate member  24  may be provided as a printed circuit board, or may be of a polymer material, and may be flexible or rigid. Alternatively, the third plate member  24  may be of a semiconductor material or a ceramics material. A plurality of activating means, in this embodiment of the invention provided by thin film resistor heating elements  28  are arranged in a matrix on the first major surface  25  of the third plate member  24  for raising the temperature of the expandable driving substance  18  in the respective second chambers  16  for expansion thereof. The heating elements  28  are aligned with the respective second chambers  16 . The thin film resistors forming the heating elements  28  may be formed by any suitable process, which will be dependent on the material of the third plate member  24 . 
     The third membrane  27  is sealably secured to the second major surface  15  of the second plate member  12  for sealably closing the ends of the second chambers  16  adjacent the second major surface  15 . The third membrane  27  is of a heat insulating material, which is impermeable to the driving substance, and is provided with a matrix of openings  29  which are sealably closed by a plurality of heat conductive elements, namely, heat conductive discs  30  of metal material for facilitating heat transfer between the heating elements  28  and the driving substance  18  in the corresponding second chambers  16 . The provision of the third membrane  27  as a heat insulating material minimises heat transfer between each heating element  28  and the second chambers  16  other than the corresponding adjacent second chamber  16 , so that activation of each heating element  28  causes the driving substance in the corresponding second chamber  16  only to expand. 
     An electronic circuit  31  is also formed in or on the third plate member  24 , and depending on whether the third plate member  24  is provided as a printed circuit board or as a semiconductor substrate, the circuit  31  may be formed on the first and/or second major surfaces  25  and  26 , and/or within layers as will be understood by those skilled in the art. However, in a case where the third plate member  24  is provided as a semiconductor substrate, the circuit  31  may be formed as an integrated circuit on layers  32  of the substrate of the plate member  24 , as illustrated in  FIG. 8 . The circuit  31  comprises a plurality of transistor switches  34 , one transistor switch  34  being provided for each heating element  28  through which an electrical power supply is provided to the respective heating elements  28  for facilitating independent addressing of the respective heating elements  28 . The heating elements  28  are powered through the transistors  34  and in turn through corresponding fuses  35  which are formed by thin film elements. Each thin film element which forms a fuse  35  is sized so that after conducting current to the corresponding heating element  28  for a predetermined time period, the fuse  35  goes into a permanent open circuit state, thereby preventing further activation of the corresponding heating element  28 . The fuses  35  are rated so that the predetermined time period during which each fuse  35  conducts a current prior to going into an open circuit state is sufficient to raise the temperature of the driving substance  18  in the corresponding second chamber  16  for in turn urging the corresponding solid form structure  2  into penetrating engagement in the skin of a subject. 
     A programmable logic circuit  37  is also provided for operating the heating elements  28  in a desired sequence for urging the solid form structures  2  individually or in groups into penetrating engagement with the skin of the subject in accordance with a predefined treatment regime. For example, the programmable logic circuit  37  could be programmed to operate the heating elements  28  in groups, so that the respective groups would be sequentially operated at predefined time intervals over a predefined treatment period. The predefined time intervals could be such as to facilitate administration of a dose of the active substance three times per day, for example, in the morning, afternoon and evening, and the predefined treatment period could be a period over a number of days, for example, five days, seven days or the like. The number of heating elements  28  in each group would be dependent on the dose size, and in cases where the required dose size could be supplied by a single one of the solid form structures  2 , the heating elements  28  would be individually operable. Depending on the material of the third plate member  24 , the programmable logic circuit  37  may be formed as an integrated circuit on the third plate member  24 , or may be provided separately for attachment to the device  1 , for example, for attachment to the third plate member  24 . 
     A monitoring circuit  38  is also provided for monitoring the state of the fuses  35  for in turn determining the first chambers  8  from which the solid form structures  2  have already been urged into penetration with the skin of the subject. Depending on the material of the third plate member  24 , the monitoring circuit  38  would be provided in a similar manner to that in which the programmable logic circuit  37  is provided. 
     A power supply, in this embodiment of the invention provided by a battery  40 , may be integrally formed with the delivery device  1  or independently thereof for coupling to the delivery device  1 . In this embodiment of the invention the battery  40  is formed in one or more of the first and/or second chambers  8  and  16  by placing an electrolyte in the appropriate ones of the first and/or second chambers  8  and  16 . Suitable electrodes  41  are provided in the appropriate ones of the first and/or second chambers  8  and  16  to co-operate with the electrolyte to in turn provide electrical power to the integrated circuit  31  and to the heating elements  34  through the transistors  34  and the fuses  35 . An input/output interface  42  is provided on the third plate member  24  for facilitating programming of the programmable logic control circuit  37 . The input/output interface  42  may be adapted to facilitate wireless programming of the programmable logic circuit  37 . 
     It is also envisaged that the programmable logic control circuit may be programmable to be responsive to externally applied signals, for example, an external signal from an external monitoring device, which would be provided for monitoring a particular characteristic of the subject. On the monitoring device indicating an abnormal situation, one or more of the heating elements  28  corresponding to one or more solid form structures  2  would be activated for urging those solid form structures  2  into penetrating engagement with the skin of the subject. The programmable logic circuit may also be programmable to be responsive to environmental sensors, which could be worn on the body of a subject, so that in the event of a change or an occurrence in the environment the heating elements  28  corresponding to appropriate ones of the solid form structures  2 , which would be provided with a suitable active substance would be activated for administering the active substance to the subject. For example, such an environmental change could be an increase in the pollen count in the atmosphere, which would necessitate administering an antihistamine substance to the subject, and in which case the active substance in the appropriate ones of the solid form structures would be an antihistamine substance. 
     It is also envisaged that the device  1  may button operated manually by the subject. In which case, a manual button operated switch would be provided on the device  1 , for example, on the third plate member  24 , and the button switch would be coupled to the programmable logic circuit  37 , so that on operating the button switch, the programmable logic circuit  37  would operate the appropriate one or ones of the heater elements  28  in order to activate the driving substance  18  for in turn urging the corresponding solid form structure or structures  2  to penetrate through the skin of the subject. 
     Returning now to the driving substance  18 , the driving substance  18  may be any suitable solid, liquid or gas which has a relatively high coefficient of expansion. In this embodiment of the invention expansion of the driving substance is in response to a temperature increase, and is provided by a plurality of gas filled microspheres located in the respective second chambers  16 . The microspheres are of the type supplied under the Trade Mark EXPANCEL. The microspheres are small gas filled spherical particles of plastics material. The shells of the microspheres are of a thermoplastic polymer which softens in response to a rise in temperature, resulting in a dramatic increase in the volume of the microspheres as the gas contained therein expands also in response to the rise in temperature. When in an unconfined space, such microspheres can expand to a volume which is forty times their original size. 
     Ideally, the driving substance should be such that expansion of the driving substance takes place relatively rapidly at a relatively low temperature. In the case of the gas filled microspheres, depending on their temperature rating, it has been found that by raising the temperature of the microspheres to temperatures in the range of 70° C. to 130° C., adequate expansion is achieved for driving the corresponding solid form structure  2  through the corresponding first chamber  8  for penetrating the skin of the subject. 
     Alternatively, the driving substance may be a solid which on being subjected to heat converts directly to a gas, such as Azobisisobutylonitrile (AIBN). Needless to say, the driving substance may be a liquid which on being heated converts to a gas, or the driving substance may be a gas with a high coefficient of expansion. 
     As mentioned above, the delivery device  1  is of micro-dimensions, and the first plate member  7  is of thickness t 1  of approximately 0.6 mm, see  FIG. 2 . The second plate member  12  is of thickness t 2  of approximately 1.0 mm. Each first chamber  8  is of circular transverse cross-section and is of diameter of approximately 0.5 mm, and each second chamber  16  is of circular transverse cross-section and of diameter of approximately 0.5 mm. The base portion  4  of each solid form structure  2  is of constant circular transverse cross-section of diameter d just less than 0.5 mm, so that the base portion  4  of each solid form structure  2  is a smooth sliding fit in the corresponding first chamber  8  from a position within the first chamber  8  to a position projecting through the second membrane  22  for penetrating the skin of a subject. The axial thickness t 3  of the base portion  4  is approximately 0.07 mm. The tapered portion  6  of each solid form structure  2  is of conical shape and the overall axial length l of each solid form structure  2 , including the thickness t 3  of the base portion  4  is approximately 0.5 mm. The thickness of the third plate member  24  will depend on the material thereof, but typically, will be of the order of 2.0 mm. 
     An adhesive patch  44  having an adhesive surface  45  is bonded to the second major surface  26  of the third plate member  24 , and an outer peripheral portion  46  of the adhesive patch  44  is provided for bonding the adhesive patch  44  with the delivery device  1  attached thereto to the skin of a subject with the second membrane  22  abutting the skin of the subject. 
     In use, with the first, second and third plate members  7 ,  12  and  24  and the first and third membranes  20  and  27  assembled, and with the solid form structures  2  located in the first chambers  8  and the second membrane  22  sealably secured to the first major surface of the first plate member  7 , and with the programmable logic control circuit  37  appropriately programmed, the delivery device  1  is attached to the skin of the subject at the appropriate site by the patch  44 . At the appropriate programmed or otherwise timed predefined time intervals during the predefined treatment period, the appropriate one or ones of the heating elements  28  are powered up for expanding the driving substance  18  in the corresponding second chamber or chambers  16 , for in turn urging the corresponding one or ones of the solid form structures  2  to penetrate through the second membrane  22 , and in turn to penetrate the skin of the subject for transdermally delivering the active substance to the subject. Depending on the volume of the active substance to be administered to the subject in each dose, either one or an appropriate number of the heating elements are activated. On penetrating the skin of the subject, the scaffolding structure  3  of each solid form structure  2  may serve to facilitate a slow release of the active substance or otherwise from the corresponding solid form structure  2 . Additionally, as the active substance is being slowly delivered to the subject, the scaffolding of the solid form structure gradually dissolves. 
     Thus, depending on the volume of the active substance to be administered to the subject in each dose, the heating elements  28  individually are sequentially activated at the appropriate predefined intervals over the predefined treatment period during which the doses of the active substance are to be administered to the subject, or alternatively, respective groups of the heating elements are sequentially activated at the appropriate predefined time intervals over the predefined treatment period. 
     It is envisaged that the solid form structures of the delivery device may each comprise the same active substance, or alternatively, respective groups of the solid form structures may comprise different active substances. This would facilitate the administration of more than one active substance to a subject over a predefined treatment period. Different ones of the active substances may be administered to the subject simultaneously, or at different times during the predefined treatment period. 
     Referring now to  FIGS. 12 and 13 , there is illustrated a micro-dimensioned delivery device according to another embodiment of the invention, indicated generally by the reference numeral  50  for administering an active substance transdermally to a subject. The delivery device  50  is substantially similar to the delivery device  1 , and similar components are identified by the same reference numerals. In this embodiment of the invention the second and third plate members are formed by a single integral plate member  51 , which typically comprises a polymer material. The second chambers  16  are formed in the plate member  51  and extend into the plate member  51  from a first major surface  52  thereof. The activating means are provided by electrically powered heating elements  53  formed as thin film resistors in respective bases  54  of the corresponding second chambers  16 . The heating elements  53  formed by thin film resistors, and are powered through an electronic circuit similar to the circuit  31  described with reference to the device  1 . Wires (not shown) or other suitable electrically conductive tracks through the polymer material of the plate member  51  supply electrical power to the heating elements  53 . If the plate member  51  is provided as a semiconductor substrate, the heating elements may be formed on the bases  54  of the second chambers  16  by a suitable integrated circuit forming process, for example, by chemical vapour deposition. Typically, an insulating layer, for example, a silicon oxide layer (not shown) would be provided over the heating elements  53 . An integrated circuit (not shown) but substantially similar to the circuit  31  would also be provided in the plate member  51 . 
     Otherwise, the delivery device  50  is substantially similar to the delivery device  1 , and its use and operation are also similar to the delivery device  1 . 
     Referring now to  FIGS. 14 to 19 , there is illustrated a micro-dimensional delivery device  60  according to another embodiment of the invention for administering an active substance transdermally to a subject. The delivery device  60  is substantially similar to the delivery device  1 , and similar components are identified by the same reference numerals. In this embodiment of the invention a locating means is provided for locating the first and second plate members  7  and  12  relative to each other, so that the first and second chambers  8  and  16  are aligned with each other, and the locating means comprises respective pairs of interengageable complementary formations. One of the formations of each pair of formations comprises an annular projection  61  extending from the second major surface  10  of the first plate member  7 , and the other of each pair of formations comprises a recess formed by an annular groove  62  extending into the first major surface  14  of the second plate member  12  for engaging the corresponding projection  61 . Each annular projection  61  is of circular shape and extends from the second major surface  10  of the first plate member  7  completely around the corresponding first chamber  8  and slightly radially spaced apart therefrom. Each annular groove  62  extends completely around the corresponding second chamber  16  and slightly radially spaced apart therefrom. The annular projections  61  and the annular grooves  62  are dimensioned for accommodating the first membrane  20  therebetween as the first and second plate members  7  and  12  are brought into engagement with the first membrane for entrapping the first membrane between the annular projections  61  and the corresponding grooves  62 . 
     Otherwise, the delivery device  60  is similar to the delivery device  1  and its use and operation are also similar to the delivery device  1 . 
     Referring now to  FIGS. 20 to 25 , there is illustrated a micro-dimensioned delivery device  70  according to another embodiment of the invention for administering an active substance transdermally to a subject. The delivery device  70  is substantially similar to the delivery device  1 , and similar components are identified by the same reference numerals. The main difference between the delivery device  70  and the delivery device  1  is in the provision of a locating means between the first and second plate members  7  and  12  for locating the first and second plate members  11  and  12  with the first and second chambers  8  and  16  aligned. In this embodiment of the invention the locating means comprises respective pairs of interengageable complementary formations, one of which formations is formed by an annular projection  71  extending from the second surface  10  of the first plate member  7  and a corresponding annular recess  72  formed in the first major surface  14  of the second plate member  12 . The annular projections  71  are similar to the annular projections  61  of the delivery device  60 , with the exception that the inner diameter of each annular projection  61  is similar to the diameter of the corresponding first chamber  8 . In other words, the annular projections  71  are not spaced apart from the first chambers  8 . The annular recesses  72  in this embodiment of the invention are formed into the second chambers  16  adjacent the first major surface  12  of the second plate member  12 . The annular recesses  72  and the projections  71  are dimensioned for accommodating the first membrane  20  therebetween when the first and second plate members  7  and  12  are brought into engagement with each other with the first membrane  20  entrapped by the co-operating action of the annular projections  71  with the corresponding annular recesses  72 . 
     Otherwise, the delivery device  70  and its use and operation are similar to the delivery device  1 . 
     Referring now to  FIG. 26 , there is illustrated a micro-dimensioned delivery device  80  according to another embodiment of the invention for administering an active substance transdermally to a subject. The delivery device  80  is substantially similar to the delivery device  1 , and similar components are identified by the same reference numerals. The main difference between the delivery device  80  and the delivery device  1  is that in this embodiment of the invention the third membrane has been omitted, and the third plate member  24  is provided as a flexible polymer sheet which is sealably secured to the second major surface  15  of the second plate member  12  for sealing the second chambers  16 . Electrical heating elements  28 , which are formed by thin film resistors, are formed on the first major surface  25  of the third plate member  24 . An electronic circuit (not shown, but similar to the circuit  31  of the device  1 ) is provided on the second major surface  26  of the third plate member  24 . Electrically conductive wires or suitable electrically conductive tracks couple the heating elements  28  to the circuit provided on the second major surface  26  of the third plate member  24  through vias (not shown) through the third plate member  24 . 
     Otherwise, the delivery device  80  and its use and operation is similar to the delivery device  1 . 
     Referring now to  FIG. 27 , there is illustrated an injectable element according to another embodiment of the invention, which is provided by a solid form structure indicated generally by the reference numeral  90 , for use in any of the delivery devices  1 ,  50 ,  60 ,  70  or  80  already described. In this embodiment of the invention the solid form structure  90  comprises a mixture of an active substance and an excipient. The active substance and the excipient are mixed together with an appropriate binder to set to form the solid form structure in the form of a solid. In this embodiment of the invention a lattice scaffolding structure is not required. 
     It is also envisaged that when preparing the injectable elements, whether they be prepared in the form of the solid form structure  2  or in the form of the solid form structure  90 , the injectable element may be prepared with the active substance located in the tapering portion  6  towards the tip  5 , in order to ensure that when the solid form structure penetrates through the skin of the subject to the site beneath the skin of the subject, the active substance is concentrated at the appropriate site. In which case, the remainder of the tapering portion  6  and the base portion  4  would not include any active substance. 
     It is envisaged that in cases where the programmable logic control circuit is programmable in a wireless manner, the electronic circuit  31  of the relevant devices would be provided with wireless connectivity and would be programmable by, for example, Bluetooth. 
     In certain cases, it is envisaged that the power to the delivery device may be supplied by kinetic movement, as for example in an automatic watch, whereby the kinetic movement may be converted to electrical energy for charging a battery, or for charging a capacitor or other suitable electrical energy storing device. 
     While the urging means for urging the solid form structures  2  to penetrate the skin of the subject has been described as being provided by gas filled microspheres sold under the Trade Mark EXPANCEL, any other suitable gas filled microspheres may be used. Needless to say, other suitable driving substance may be used, and such other driving substances may, for example, be an expandable liquid, an expandable solid or an expandable gas. It is also envisaged that the driving substance may be a solid which would convert directly from the solid phase to the gaseous phase. Additionally, it is envisaged that other suitable urging means besides a driving fluid may be used. In certain cases, it is envisaged that the driving substance may comprise two chemicals, such that when mixed, the chemicals would expand to urge the first membrane into the corresponding first chamber. In which case, the two chemicals would be maintained separated from each other until the corresponding solid form structure is to be urged from the corresponding first chamber. The two chemical substances could be maintained separated from each other by a suitable membrane, which would be burstable by a suitable activating means. 
     Needless to say, while the driving substance has been described as being provided by gas filled microspheres which expand at a relatively low temperature, in certain cases, it is envisaged that a driving substance which converted from the liquid phase to a gaseous phase at a higher temperature, and indeed, at a relatively high temperature, may also be suitable. 
     Further, it is envisaged that the driving substance may be a porous material which would be impregnated with a gas of high co-efficient of expansion or a liquid which would convert to a gaseous phase at an appropriate temperature, and when subjected to the appropriate temperature the gas would expand or the liquid would convert to the gaseous phase. The expanding gas would cause expansion of the porous material, which would in turn urge the first membrane into the corresponding first chamber. Alternatively, the expanding gas may expand out of the porous material to directly act on the first membrane to urge the first membrane into the corresponding first chamber. 
     Additionally, each urging means may be provided by a piston which would be sealably located in the corresponding second chamber, and would be sealably slideable into and through the corresponding first chamber in response to expansion of a driving substance. It is also envisaged that the solid form structures may be sealably slideable longitudinally in the first chambers, and the driving substance would act directly on the solid form structures for urging the solid form structures through the first chambers for penetrating the skin of the subject. 
     While the delivery devices have been described for administering an active substance transdermally to a subject, the delivery devices may be adapted for delivering an active substance to a subject subcutaneously, intradermally, or to any other depth beneath the skin of the subject. This would be achieved by providing the solid form structures to be of an appropriate axial length. 
     Additionally, it will be appreciated that while the active substance has been described as being incorporated in a solid form structure which is formed by a scaffolding structure of a biodegradable polymer material, the scaffolding structure may be provided by any suitable type of biodegradable lattice structure, indeed, a non-biodegradable material, polymer or otherwise, or indeed any other suitable bio-compatible material may be used for forming a lattice structure which would be suitable for being impregnated with the active substance. Additionally, in certain cases, it is envisaged that the active substance may itself be formed into the solid structure without any other ingredients or components in the structure, or the active substance may be formed into the solid form structure in a mixture comprising only the active substance and an excipient as described with reference to  FIG. 27 . 
     It is also envisaged that the delivery devices may be supplied without the solid form structures, and in which case, the solid form structures would be placed in the first chambers subsequently, which would then be sealed with the second membrane. The subsequent assembly of the solid form structures into the first chambers could be carried out by a user of the device, or alternatively, could be carried out under factory sterile conditions. 
     It is also envisaged that the second membrane may be omitted or may be provided to be peeled off just prior to use, so that the first major surface of the first plate member would be in direct engagement with the skin of the subject. 
     It is also envisaged that the solid form structures may be bonded to the first membrane, and in which case, it is envisaged that the driving substance in the second chambers would be of a type that once expanded would remain in the expanded state. 
     It will be appreciated that the delivery devices according to the invention may be of any size, and may comprise any number of first and second chambers and any number of solid form structures. In general, the size and the number of the first and second chambers will depend on the size and number of the solid form structures. Additionally, the number of solid form structures will be determined by the number of solid form structures required to provide each dose of the active substance, and the number of doses of the active substance in a treatment regime. Needless to say, while the first and second chambers and the solid form structures have been described as being of specific dimensions, the first and second chambers and the solid form structures may be of any suitable dimensions. 
     While the delivery devices have been described as having a second chamber corresponding to each first chamber, it is envisaged in certain cases that a number of first chambers may be provided to a single chamber. For example, in cases where a single dose of the active substance requires a number of solid form structures to be simultaneously delivered from the first chambers, a single second chamber may be provided corresponding to the appropriate number of first chambers in order to supply the single dose of the active substance. Indeed, in certain cases, it is envisaged that where the delivery device is to be provided as a single dose device, the delivery device may be provided with only one single second chamber which would be operated to simultaneously discharge the solid form structures from all the first chambers. 
     While the activating means have been described as being specific types of electrically powered heating elements, any suitable type of heating elements may be used. Additionally, other suitable types of activating means besides heating elements may be used. In general, it is envisaged that the number of activating means will be similar to the number of second chambers, although, not necessarily.