Abstract:
Embodiments of the invention provide an architecture, system and methods for optimizing power utilization for transdermal iontophoretic drug delivery which maintain a iontophoretic driving voltage at a reduced or even minimum value to support an iontophoretic delivery current. The reduced voltage reduces the power requirements for a transdermal iontophoretic delivery system during a period of drug delivery. Embodiments of an architecture for implementing this approach can utilize a controller which compares the desired current to the actual current and adjusts the voltage to reduce the amount of power used for iontophoretic drug delivery. The controller can comprise a state machine or microprocessor. Embodiments of the invention are particularly useful for extending the battery life of transdermal iontophoretic drug delivery systems.

Description:
RELATED APPLICATIONS 
       [0001]    This application is a divisional of U.S. application Ser. No. 13/024,295, entitled “Methods and Architecture for Power Optimization of Iontophoretic Transdermal Drug Delivery”, filed Feb. 9, 2011, which claims the benefit of priority of U.S. Provisional Patent Application Ser. No. 61/303,284, entitled “Methods and Architecture for Power Optimization of Iontophoretic Transdermal Drug Delivery”, filed Feb. 10, 2010; both of which are fully incorporated by reference herein for all purposes. 
     
    
     FIELD OF THE INVENTION 
       [0002]    Embodiments described herein relate to methods for power optimization for transdermal drug delivery systems. More specifically, embodiments described herein relate to methods for power optimization of iontophoretic transdermal drug delivery systems. 
       BACKGROUND 
       [0003]    The typical form of treatment for a number of medical conditions such as diabetes, iron deficiency anemia and cancer includes oral and intravenous drug delivery. However, both oral and intravenous forms of drug delivery treatment for these and other conditions have a number of limitations. In many cases, oral delivery can have poor absorption particularly in the presence of other medications as well as a number of side effects. Intravenous limitations include the requirement to mix and store the medication in liquid form as well as the use of sterile techniques in administration. These can be particularly problematic in third world countries where adequate refrigeration and sterile needles are not readily available, limiting shelf life and exposing the patient to infection. Also, IV administration can include several risk factors including anaphylaxis and cardiovascular complications. Thus, there is a need for improved methods of drug delivery for many forms of treatment. 
         [0004]    Transdermal iontophoresis is a non-invasive method of propelling high concentrations of drug or other therapeutic agents through the skin by repulsive electromotive force using a small electrical charge. In order to facilitate ease of use to the patient, iontophoretic transdermal devices are portable and thus include a portable power source such as a battery so that the device can be worn or carried by the patient. Further, in some instances it is desirable for such power sources to be able to provide power for a period of hours each day possibly over multiple days in order to allow the patient to receive a selected drug during this period. Thus battery life can be a factor in the usability of a transdermal iontophoretic delivery device for the patient so that patient need not change batteries over the course of a single treatment or even over many treatments. Thus there is a need for approaches for improving battery life for transdermal iontophoretic delivery devices and systems. 
       BRIEF SUMMARY 
       [0005]    Embodiments of the invention provide an architecture, system and method for optimizing power used for the transdermal iontophoretic delivery of drugs and other therapeutic agents. Many embodiments provide an architecture, system and method for optimizing power used for the transdermal iontophoretic delivery of drugs and other therapeutic agents wherein the voltage used for driving transdermal iontophoresis (the driving voltage) is adjusted responsive to electrical parameters in the architecture and/or electrical circuit used for transdermal iontophoretic drug delivery. Such parameters can include the actual iontophoretic current, the total or lumped (herein total) resistance/impedance of the iontophoretic transdermal delivery circuit or the tissue resistance/impedance at the iontophoretic delivery site. As used herein, resistance refers to embodiments using a direct current for the iontophoretic delivery current and impedance refers to embodiments using an alternating current for the iontophoretic delivery current. In particular embodiments using an AC iontophoretic delivery current, the driving voltage is adjusted responsive to the total impedance between two electrodes used for iontophoretic current delivery. 
         [0006]    In various aspects, the invention provides an approach for optimizing power utilization for transdermal iontophoretic drug delivery which maintains the iontophoretic driving voltage at the minimum value it takes to support a desired iontophoretic delivery current. Since the tissue impedance can change over time (e.g., due to tissue heating and changes the ion concentration in tissue), it is desirable to also change the iontophoretic voltage. Embodiments of this approach can utilize a controller which compares the desired delivery current to the actual delivered current and adjusts the driving voltage such that power used for iontophoretic delivery is reduced and even minimized. This in turn, extends both battery life and the delivery period for iontophoretic drug delivery. Thus, over the course of a drug delivery regimen of days, or even up to one to two weeks, a user need not remove a wearable iontophoretic delivery system to change a battery. This improves compliance with a particular drug delivery regimen and in turn, helps to maintain the desired concentration of drug in the patient&#39;s body over the course of a delivery period. This serves to improve clinical outcomes while reducing the incidence of over and/or under delivery of drug. Embodiments of the invention are particularly useful for improving compliance with drug delivery regimens over long periods of time such as those used for iron deficiency anemia, chemotherapy, pain management, diabetes, hypertension, blood volume management and other related conditions and diseases. 
         [0007]    In one aspect, the invention provides a method for optimizing power for iontophoretic transdermal delivery of a therapeutic agent to a patient comprising applying a patch to a skin, with the patch comprising a therapeutic agent and at least one electrode. Typically, at least two electrodes will be applied, though three, four or even greater numbers may applied. The electrodes are then coupled to a power source comprising electrical circuitry and one or more portable batteries or other electrical storage means. Collectively, the patch and power source comprise an iontophoretic delivery system and the power source, patch and patient&#39;s skin comprise an iontophoretic delivery circuit for iontophoretic delivery. A selected current is then delivered to the skin from the power source through the patch/electrode to transport the therapeutic agent into the skin (using an electromotive force). An electrical parameter of the iontophoretic delivery circuit is then measured. Typically, this will include either the actual current delivered to tissue (herein delivery current) or the total resistance/impedance of the iontophoretic delivery circuit, though other resistance/impedance values are also considered. The voltage used to supply the delivery current to skin is adjusted responsive to the measured electrical parameter, wherein the voltage is adjusted to maintain the selected delivery current while minimizing power delivered from the power source. In many embodiments, the delivery current is an alternating current which can have a frequency in the range of 0.5 to 100 hz. Typically, the power source is an electrochemical battery such as a lithium or lithium ion or alkaline battery. The life of the battery can be extended as a result of the minimized delivered power. The minimized power can also be used to maintain the voltage and/or current of the battery above a minimum level during a period of transdermal therapeutic agent delivery. The delivery period can extend from several days, to a week or two or longer. In use, this approach allows the patient to wear and/or use a transdermal iontophoretic delivery device for a period of days or weeks or longer without having to take off the device to replace the batteries. This in turn, improves patient compliance with a medicinal regimen and helps maintain in vivo concentrations of the selected therapeutic agent at therapeutically effective levels improving clinical outcomes. 
         [0008]    Another aspect the invention provides circuit architectures (herein architectures) for optimizing power for the iontophoretic transdermal delivery of a therapeutic agent. In one embodiment the architecture comprises a first and second electrode, a power source operably coupled with the first and second electrodes, a current source operably coupled to at least one of the first and second electrodes, a measurement device operably coupled to the current source and a controller operably coupled to the measurement device and the power source. At least one of the electrodes is positioned in or on or otherwise operably coupled to an iontophoretic transdermal patch for delivering the therapeutic agent to the patient. The power source can comprise a voltage source such as an electrochemical storage battery (e.g., lithium alkaline, etc.) and a voltage converter operably coupled to the voltage source. In such embodiments, the controller can be operably coupled to the voltage regulator. The controller can comprise one or more of a microprocessor or other digital controller, or a state device or other analog controller. The controller can also include logic for utilizing an input from the measurement device to generate an output sent to the voltage regulator so as to maintain current from the current source above a threshold level while minimizing power drawn from the power source including the battery. For digital embodiments of the controller the logic can be incorporated into one or more software modules which are operable on the controller and may be resident within the controller or stored in a memory device coupled to the controller. The measurement device can be configured as an impedance (resistance) measurement device, a current measurement device or other related electrical property measurement device known in the art, and may utilize Ohms law for measuring one or more electrical properties. In various embodiments the measurement device may include a resistor and operational amplifier (herein op-amp) or other amplifier device/circuit. For digitally based embodiments of the controller, the measurement device may also include an analog to digital converter (herein an A/D converter) for converting output signals from the measurement device into digital form. In such embodiments all components of the measurement device can be fabricated on a single integrated circuit. Also, all or portions of the entire architecture can be fabricated on a single integrated circuit such as an ASIC or other related circuit. 
         [0009]    Further details of these and other embodiments and aspects of the invention are described more fully below, with reference to the attached drawing figures. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0010]      FIG. 1  is a cross sectional view showing the three main layers of the skin, the epidermis, the dermis and subcutaneous tissue as well as the passageways into the skin. 
           [0011]      FIG. 2  is a lateral view of an embodiment of a system for the transdermal iontophoretic delivery of various therapeutic agents using delivery and lateral electrodes. 
           [0012]      FIG. 3   a  is a schematic side view showing placement of an embodiment of a transdermal iontophoretic patch device on the surface of the skin, wherein the device comprises an active electrode assembly and a return electrode assembly. 
           [0013]      FIG. 3   b  is a schematic side view showing placement of an embodiment of transdermal iontophoretic patch device on the surface of the skin, wherein the device comprises two active electrode assemblies. 
           [0014]      FIGS. 4   a  and  4   b  are side and top views showing an embodiment of a skin patch including an active electrode and lateral electrodes. 
           [0015]      FIG. 5  is a schematic view showing an embodiment of a power optimizing architecture for use with iontophoretic transdermal drug delivery systems. 
           [0016]      FIG. 6  is a flowchart of an algorithm of power optimization for use with iontophoretic transdermal drug delivery systems. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0017]    Many embodiments described herein provide a device, system and method for the transdermal iontophoretic delivery of various therapeutic agents. As used herein, the term transdermal delivery refers to the delivery of a compound, such as a drug or other therapeutic agent, through one or more layers of the skin (e.g., epidermis, dermis, etc). Referring now to  FIG. 1 , the layers of the skin include the epidermis EP, dermis D and subdermis SD. The upper most layer of the epidermis includes the stratum corneum SC, a dead layer of skin (having a thickness of about 10 to 40 μm) and the viable epidermis EP. Transdermal delivery can proceed by one of the three passage ways into the skin, via 1, the sweat pores SP, 2, the hair follicles HF or via permeation 3 through the epidermis EP (starting at the stratum corneum) and the dermis. 
         [0018]    Iontophoresis is a non-invasive method of propelling high concentrations of a charged substance, known as the active agent, transdermally by repulsive electromotive force using a small electrical charge. The active agent can include a drug or other therapeutic agent. The charge is applied by an electrical power source to an active electrode assembly placed on the skin which contains a similarly charged active agent and a solvent in which it is dissolved. Current flows from the electrode assembly through the skin and then returns by means of a return or counter electrode assembly also placed on the skin. A positively charged electrode assembly, termed the anode will repel a positively charged active agent, or anion, into the skin, while a negatively charged electrode assembly, termed the cathode, will repel a negatively charged active agent, known as a cation into the skin. 
         [0019]    Referring now to  FIGS. 2-5 , an embodiment of a system  5  for the transdermal iontophoretic delivery of a therapeutic agent  51  to a tissue site TS (such as the arm A) also referred to as a delivery site, on the skin S of patient, comprises at least two electrode assemblies  14  ( FIG. 5 ) including an active electrode assembly  20  and a return electrode assembly  30 ; and a power supply  100 . Active electrode assembly  20  is used to deliver the therapeutic agent through skin S via current delivered to the skin from power supply  100 . Return electrode assembly  30  provides a return path for current to power supply  100 . Collectively, the active and return electrode assemblies  20  and  30  comprise a transdermal iontophoretic delivery device  10  also described herein as patch device  10 . In embodiments using an alternating current, both electrode assemblies  14  can be configured as active and return electrode assemblies  20  and  30  depending on the direction of current flow. In some cases for sake of brevity, electrode assembly  14 , active electrode assembly  20  and/or return electrode assembly  30  will sometimes be referred to as electrode  14 , active electrode  20  and return electrode  30 . 
         [0020]    In many embodiments, the electrode assemblies  14  (e.g., active and return assemblies  20  and  30 ) comprise or are otherwise disposed on one or more patches  15  configured to be applied to the skin surface. Patches  15  are conformable to a contour CR of a skin surface S and can be fabricated from layers of elastomeric or other flexible polymer material. In some embodiments, two or more electrode assemblies  14  including active and return electrode assemblies  20  and  30  can be placed on a single patch  15 . In other embodiments, system  5  can include separate patches  15  for electrode assemblies  14 , for example, a first patch  15 ′ for the active electrode assembly  20  and a second patch  15 ″ for the return electrode assembly  30 . In other embodiments, three or more patches  15  can be used so as to have either multiple active electrode assemblies  20  or return electrode assemblies  30  or both. For example, in one embodiment system  5  can comprise three patches  15 ; including two patches containing active electrode assemblies  20  and a third patch  15  containing a return electrode assembly  30 . Other combinations of multiple patches and electrode assemblies are also contemplated, e.g., four patches, two for active electrode assemblies  20  and two for return electrode assemblies  30 . 
         [0021]    In many embodiments, active electrode assembly  20  can comprise a reservoir  21  for the therapeutic agent, a tissue contacting porous portion  24  in fluidic communication with the reservoir, an adhesive portion  25  for adhering the assembly to the skin, and an electrical connector  26  for coupling the electrode assembly  20  to an electrical power supply  100  as is shown in the embodiment of  FIG. 4   a.  Reservoir  21  can be sized for the particular dose of therapeutic agent to be delivered. In various embodiments, the power supply  100  can include various features to facilitate use by medical personnel both in a hospital setting and in the field. For example, the power supply can include or be configured to be coupled to a bar code reader (not shown) for reading bar codes positioned on one or more of electrode assemblies  14 , patches  15  or power supply  100 . 
         [0022]    Tissue contacting portion  24  is also conductive by virtue of being fabricated from conductive porous materials (e.g., conductive fibers) or becomes conductive by becoming wetted with conductive solution  54  (the conductivity being due to agent  51  or various electrolytes added to the solution) and thus functions as an electrode  20 . Connector  26  can extend into or otherwise make electrical contact with tissue contacting portion  24 . In some embodiments, connector  26  can be coupled to a conductive element  28  positioned within the electrode assembly  20  and coupled to conductive porous portion  24 . One or more of conductive element  28 , conductive layer  34  (described below) as well as lateral electrodes  40  (also described below) can comprise various conductive materials including stainless steel, carbon, AgCl or other conductive materials known in the art. 
         [0023]    Typically, the therapeutic agent  51  will be dissolved in a therapeutic agent solution  54 , also described as therapeutic agent composition  54  which is used to fill reservoir  21 . In addition to agent  51 , solution  54  can include one or more pharmaceutical excipients  52  such as preservatives. The viscosity of the solution  54  can be adjusted to have the solution readily wick from reservoir  21  into porous layer  24 . Solution  54  can be preloaded into the reservoir  21  at the factory or can be added by medical personnel prior to use through means of a port  22 , such as self sealing port allowing injection which is coupled to reservoir  21  via means of a channel  27  as is shown in the embodiment of  FIG. 3   b.  Suitable therapeutic agents  51  can include without limitation ferric pyrophosphate or other iron containing compound for the treatment of iron deficient anemia, insulin or various glucagon like peptides for treatment of diabetes or other blood sugar regulation disorder, Fentanyl or other opioid compound for pain management and various chemotherapeutic agents for the treatment of cancer such as Paclitaxel. 
         [0024]    The return electrode assembly  30  comprises a tissue contacting conductive layer  34 , an adhesive layer  35  and a connector  26  for coupling the electrode assembly to the electrical power source. In many embodiments, the return electrode assembly  30  can have substantially the same elemental configuration as active electrode assembly  20  (e.g., a reservoir  21 , conductive tissue contacting layer  24 ) so as to function as an active electrode assembly as is shown in the embodiment of  FIG. 3   b.    
         [0025]    In many embodiments, patch  15  also includes one or more pair of electrodes known as lateral electrodes  40 . Lateral electrodes  40  can be placed on either side of porous portion  24  at a selectable distance from the perimeter  24 p of porous portion  24  as is shown in the embodiments of  FIGS. 3   a - 3   b  and  4   a - 4   b.  Electrodes  40  can comprise various conductive materials including metals, graphite, silver chloride and other like materials. In various embodiments, all or a portion of electrode  40  can include an insulative coating so as to be a capacitively coupled electrode that delivers current to the skin via capacitive coupling. Electrodes  40  can be electrically isolated from electrodes  20  and  30  will typically include their own wave form generator circuits. 
         [0026]    The lateral electrodes  40  are arranged with respect to porous portion  24  such that they result in a conductive pathway  104  which goes through the skin S underlying portion  24  and is substantially parallel to the skin. Embodiments of patch  15  that employ lateral electrodes  40  with delivery electrodes  20 , allow for the flow of two currents, a first current  60  and a second current  70 . First current  60  flows between electrodes  20  and  30  and serves to provide an electromotive force which acts to drive the therapeutic agent  51  into and across the layers of the skin S. The second current  70 , known as sieving current  70 , provides an electromotive force that acts on the therapeutic agent  51  in a direction parallel to the skin S so as to cause oscillation of therapeutic agent  51  in a direction parallel to skin S. This oscillation acts to sieve the therapeutic agent through pathways of lesser or least diffusional resistance in the skin. For embodiments where second patch  15 ″ contains lateral electrodes  40  and is used to deliver therapeutic agent, a third current  70 ′ can be delivered from lateral electrodes on the second patch  15 ″ to also create a electromotive driving force  80  to oscillate the therapeutic agent substantially parallel to the skin surface underneath the second patch  15 ″. Further description on the arrangement and use of lateral electrodes  40  including use in generating a sieving current is found in U.S. Provisional Patent Application Ser. Nos. 61/152,251 and 61/221,010 which are incorporated by reference herein in their entirety. 
         [0027]    Referring now to  FIGS. 5-6 , embodiments of a power control architecture  105  for optimizing power supplied to a transdermal iontophoretic delivery system  5  will now be described. Architecture  105  can be configured to optimize power used by system  5  for iontophoretic drug delivery to a patient at a delivery site such as the skin or other site on or within the body (e.g., the eye, the tympanic membrane, buccal mucosa, intestinal mucosa, etc.). This, in turn, reduces power consumption and extends battery life of system  5  or other transdermal iontophoretic delivery system. Accordingly, embodiments of the architecture are particularly useful for extending the battery life for transdermal iontophoretic delivery systems. 
         [0028]    Architecture  105  will typically comprise a power supply  100 , at least two electrodes  14  (e.g., an active and return electrode), a controller  110 , a current source  130 , a current/impedance measurement device  140  and at least one switch  150 . Many variations to this configuration are also contemplated, including for example, the inclusion of additional electrodes, sensors, filters (e.g., high pass, low pass, band pass, etc.), communication devices (e.g., an RF ID chip), various power management devices and other electronic devices and circuitry. All or portions of architecture  105  can be fabricated or otherwise positioned on a single integrated circuit (e.g., an ASIC or application specific integrated circuit) or on multiple integrated circuits (e.g., a chip set) that are operably coupled. All or portions of architecture  105  can comprise an iontophoretic delivery circuit  106  for iontophoretic drug delivery. Typically, circuit  106  comprises power source  100 , patch/electrode(s)  14  and the patient&#39;s skin/tissue at delivery site TS. 
         [0029]    Power supply  100  will typically include at least one voltage source  120  such as a portable battery or other electrical storage means coupled to a voltage converter  125 . Suitable portable batteries include lithium, lithium ion, alkaline, or zinc-air battery with other chemistries also contemplated. As an alternative, voltage source  120  may, in various embodiments, comprise a capacitor (or other electrical storage means) or an energy harvesting device (e.g., a piezoelectric device) alone or in combination with another electrical storage means (e.g., a battery, capacitor, etc.). Voltage converter  125  serves to convert a voltage  121  from voltage source  120  to a desired voltage output voltage  127  used by architecture  105  and/or other circuitry and electrical components of system  5 . Converter  125  can be fixed (e.g., step down, or step up) or variable and may be controllable by analog or digital inputs, e.g., from controller  110  or a manual input. The converter  125  can comprise various solid state devices (e.g., an integrated circuit) known in the art. 
         [0030]    In many embodiments, power supply  100  can comprise a variable power supply  100 t which may be controlled by a controller  110  or other control means (e.g., a remote controller). In an exemplary embodiment, variable power supply  100 t comprises a portable battery  120  and a variable voltage converter  125  that is controllable by inputs  126  from controller  110 . Inputs  126  can comprise digital or analog inputs (or a combination thereof), depending upon choice of a digital or analog controller  110 . In this and related embodiments, converter  125  can be used to convert battery voltage  121  in the range from about 1.5 to 9 volts to an output voltage  127  in the range of about 10 to 100 volts, with other ranges also contemplated. 
         [0031]    Controller  110  is used to control one or more electrical parameters of system  10  including the iontophoretic driving voltage and delivery current. Typically, it will be operably coupled to one or more of power supply  100 , voltage converter  125 , current source  130  and measurement device  140 . It may also be coupled to or even integral with one or more other electrical devices, circuitry, sensors, electrodes (e.g., electrodes  20  and  30 ), communication devices (e.g., an RF chip) and other related components. Controller  110  includes or is otherwise configured to implement logic for utilizing an input such as input  147  from measurement device  140 , to generate an output signal such as single  126  to minimize power drawn from power supply  100  including battery  110  while maintaining the current used by circuit  106  above a threshold level. In this way, battery life can be extended during periods of iontophoretic transdermal drug delivery utilizing circuit  106 . Such logic can be incorporated into one or more software modules  115  described herein. 
         [0032]    In various embodiments, controller  110  can comprise a microprocessor, ASIC, state machine or other logic resource known in the art and is configured to perform one or more control functions for architecture  105 . In preferred embodiments, controller  110  comprises a digitally based controller such as a microprocessor. In some embodiments, controller  110  may include one or more control modules  115  that comprise a software program, subroutine or other electronic instruction set digitally stored within controller  110  or memory device  117  or other memory resources  118  coupled to controller  110 . Modules  115  can be configured to control one or more electrical parameters of architecture  105  and system  5  including various voltages, currents (e.g., an iontophoretic delivery current), duty cycles, total delivered current and like parameters. Modules  115  can be pre-stored in controller  110  or downloaded from a memory device  117  coupled to the controller  110  or from a separate computer or the internet or other distributed network. In various embodiments, a physician or other medical caregiver can download one more modules  115  (corresponding to one or more drug delivery regimens) wirelessly using the internet and a portable wireless communication device such as a cell phone or tablet based device such as the Apple@ Ipad®. 
         [0033]    Current source  130  is used to control the current  132 , also known as iontophoretic delivery current  132  (herein delivery current) delivered to electrode assemblies  20 . Current source  130  is typically a controllable current source and may be controlled by one or more inputs  132  (digital, analog or a combination) from controller  110  or other control means. Accordingly, current source  130  may comprise various controllable current sources known in the art including various digitally controlled programmable current sources. Switch  150  is used to control the direction of current flow from current source  130  and may correspond to an H-bridge and other devices known in the art for controlling the direction of current flow. 
         [0034]    Current measurement device  140  is configured to measure the iontophoretic delivery current delivered to the patient. It typically comprises a resistor  141 , (also described as R 2 ) an op-amp device  143  and an analog to digital (AD) converter  144 . As shown in the embodiment of  FIG. 5 , device  140  functions by measuring a voltage across a known resistor and then digitally converting that signal which is then fed into controller  110 . Specifically, a voltage  145  across resistor R 2 ,  141  is fed into op-amp device  143 , with the output  146 , digitally converted by A/D (Analog to Digital) converter  144  into a digital signal  147  that is inputted into controller  110 . Controller can then convert signal  147  into a current by applying ohms law (I=V/R). Other configurations for measuring current  132  are also contemplated. In an alternative embodiment, measurement device  140  can be an impedance measurement device that has a similar configuration to current measurement device  140  so as to measure tissue impedance (e.g., the impedance between electrode assemblies  14 ) over a range of frequencies, such as for example from about 0.01 to 1000 hz, and digitally convert that output signal into a digital signal  147  that is fed into control  110   
         [0035]    According to one or more embodiments of methods of using architecture  105 , prior to or during a period of iontophoretic drug delivery, controller  110  sends a signal  111  to set current source  130  to a desired output delivery current  131 . The actual current  132 , delivered from current source  130  is then measured by measurement device  140  by sensing the voltage across series resistor  141 , R 2  and then applying ohms law (I=V/R). Controller  110  then compares the actual and desired currents  132  and  131  and sends a signal  126  to voltage converter  125  to change the output voltage  127  to obtain the desired delivery current  131 . In addition, or as a supplement to use of current  132 , controller  110  may use other various electrical parameters of architecture  105 , and delivery circuit  106  as an input to modify the iontophoretic delivery current. Such parameters can include without limitation, the total resistance/impedance of architecture  105  and the total resistance/impedance R 1  between electrodes  14  and/or the tissue impedance at the delivery site TS. The latter value can be obtained by use of a sensor placed on or in the skin at the delivery site TS. In some embodiments, the sensor can comprise electrode  14 , such as active electrode  20 . 
         [0036]    The control algorithm used by controller  110  for controlling current  132  may comprise one or more of a proportional (P), integral (I), derivative (D), PI, or PID based algorithm. Additionally, the control algorithm may be included in a software module  115  resident within controller  110  as is described herein. 
         [0037]    R 1  is a lumped resistance representing the impedance between the electrode assemblies  14  (e.g., active and return electrode assemblies  20  and  30 ). The lumped resistance R 1  comprises the resistance/impedance of the skin and other tissue through which iontophoretic current from current source  130  passes. The total voltage (VST) required is the sum of all the voltage drops across the components of architecture  105 . These voltages are depicted as VST, VR 1 , VCS, and VR 2  as is shown in the embodiment of  FIG. 5 . Ideally though not necessarily, the voltage required by the load, VR 1 , is large compared to the other voltages (e.g., VCS, VR 2 , etc.). 
         [0038]    In particular embodiments for optimal power efficiency, Vt may be set to approximately the sum, or slightly above the sum, of the values of VR 1 , VCS, and VR 2 . Table 1, illustrates the power savings for an iontophoretic delivery system  5 /device  10  that is achieved through use of power optimization methods described herein for various currents and impedance loads. As shown in the table, power saving of 59% or more can be achieved. 
         [0000]    
       
         
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
               
                   
                   
                   
                 Vt 
                   
                   
               
               
                   
                   
                   
                 without 
                 Vt with 
               
               
                   
                   
                   
                 optimal 
                 optimal 
               
               
                 Programmed 
                 Load 
                 Required 
                 energy 
                 energy 
               
               
                 Current 
                 Impedance 
                 Stimulation 
                 method 
                 method 
                 Power 
               
               
                 (mA) 
                 (Ohms) 
                 Voltage (V) 
                 (V) 
                 (V) 
                 Savings 
               
               
                   
               
             
             
               
                 2 
                 20000 
                 40 
                 80 
                 44 
                 45% 
               
               
                 3 
                 10000 
                 30 
                 80 
                 33 
                 59% 
               
               
                 3 
                 25000 
                 75 
                 80 
                 80 
                 0 
               
               
                   
               
             
          
         
       
     
         [0039]      FIG. 6  illustrates an embodiment of a power optimization algorithm  200  for implementing methods for optimizing power used for the iontophoretic delivery of a therapeutic agent to a patient. These and related methods can be implemented using an embodiment of architecture  105  or related power optimization architecture. However, other architectures are also contemplated. It should be appreciated that the order of these steps in the algorithm is exemplary and that the steps need not be done in the sequence described. Also only a portion of the steps in the algorithm need be used and others can be added or substituted. For example, as described below, a current measurement step can be substituted with an impedance measurement step. 
         [0040]    In a step  300 , a target iontophoretic delivery current is set by communication from controller  110  to the current source  120 . Then in a step  310  a driving voltage is set to an initial value by communication from controller  110  to voltage converter  135 . Then in a step  320  current is delivered to the patient and in step  330  the delivered current is measured using current/voltage measurement device  140 . As an alternative to current measurement, step  330  may comprise an impedance measurement step. The impedance that can be measured can include one or more of the total impedance of system  5 , the total impedance between electrodes  14  and the tissue impedance at the drug delivery site. The measured and desired current (or impedance) are compared in a step  340 . If the measured current or impedance is not at the desired level, the driving/stimulations voltage is increased in a step  350 . If the current is at the desire level, then the algorithm waits a predetermined amount of time, in a wait step  360  before decreasing the driving/stimulation voltage in step  370 . The wait period can be in the range from about 0.001 to 10 seconds or longer. After step  370 , the algorithm then cycles back to current measurement step  330 . This cycle can then be repeated throughout the entire period of iontophoretic current delivery in a substantially continuous fashion or for a selected portion thereof. Examples of measuring the electrical property for selected portions of time include variable or fixed intervals in the range of about 0.001 to 1.0 second, and/or where periods between intervals may span the range of about 0.001 to 1.0 second. Moreover, the electrical property may be measured before and during the period current is delivered to the skin. The amount that the stimulating voltage is decreased or increased in steps  350  and  370  can range from about 0.01 to about 10% of the stimulating voltage with lower and higher values contemplated. In specific embodiments, the amount of voltage increase or decrease can be 0.05, 0.1, 0.25, 0.5, 1, 5, or 7.5% of the stimulating voltage. The amount of voltage increase or decrease can itself vary depending upon one or more variables such as the initial stimulation voltage levels, impedance levels and/or a user input. 
       CONCLUSION 
       [0041]    The foregoing description of various embodiments of the invention has been presented for purposes of illustration and description. It is not intended to limit the invention to the precise forms disclosed. Many modifications, variations and refinements will be apparent to practitioners skilled in the art. For example, the iontophoretic patch can be modified in size, shape and dose of therapeutic agent for different medical conditions, different tissue sites as well as for various pediatric applications. Additionally, the power optimization algorithm can also be modified for skin type, therapeutic agent dose, as well as various pediatric applications. 
         [0042]    Elements, characteristics, or acts from one embodiment can be readily recombined or substituted with one or more elements, characteristics or acts from other embodiments to form numerous additional embodiments within the scope of the invention. Moreover, elements that are shown or described as being combined with other elements, can, in various embodiments, exist as standalone elements. Hence, the scope of the present invention is not limited to the specifics of the described embodiments, but is instead limited solely by the appended claims.