IONTOPHORETIC DRUG DELIVERY SYSTEM, INCLUDING DISPOSABLE PATCH AND REUSABLE, REMOVABLE CONTROLLER

Abstract: An iontophoretic drug delivery system (10) of the present invention includes a disposable patch, a reusable controller (14), a power source (16) and an electrode assembly (20) in electrical contact with at least two reservoirs, with at least one of the reservoirs containing an active formulation to be delivered to an applied area of a patient. The patch, power source (16) and electrode assembly (20) are for a single use and/or disposable, with the controller (14) being removably engageable with the patch for frequent reuse. In addition, the controller (14) may include a second power source for delivering sufficient energy to the controller for controlling and monitoring the electrical energy delivered by the electrode assembly (20). In an alternative embodiment of the present invention, the iontophoretic drug delivery system (10) includes a multiple-pod housing (12), a controller (14), a power source (16) and an electrode assembly (20) in electrical contact with at least two reservoirs, with at least one of the reservoirs containing an active formulation to be delivered to an applied area of a patient. The housing includes three pods (24) to more easily conform to the contours of the body, with two pods each including reservoirs and the electrode assembly, and the other pod including the controller.

Description: IONTOPHORETIC DRUG DELIVERY SYSTEM. INCLUDING DISPOSABLE PATCH AND REUSABLE, REMOVABLE CONTROLLER FIELD OF THE INVENTION The present invention generally relates to iontophoretic systems for delivering drugs or medicines to patients transdermally, i.e., through the skin, and more specifically relates to an iontophoretic drug delivery system including a disposable drug-filled patch, and a removable, reusable controller. BACKGROUND OF THE INVENTION Transdermal drug delivery systems have, in recent years, become an increasingly important means of administering drugs. Such systems offer advantages clearly not achievable by other modes of administration such as avoiding introduction of the drug through the gastro-intestinal tract or punctures in the skin to name a few. Presently, there are two types of transdermal drug delivery systems, i.e., "Passive" and "Active." Passive systems deliver drug through the skin of the user unaided, an example of which would involve the application of a topical anesthetic to provide localized relief, as disclosed in U.S. Patent No. 3,814,095 (Lubens) . Active systems on the other hand deliver drug through the skin of the user using, for example, iontophoresis, which according to Stedman's Medical Dictionary, is defined as "the introduction into the tissues, by means of an electric current, of the ions of a chosen medicament." Conventional iontophoretic devices, such as those described in U.S. Patent Nos. 4,820,263 (Spevak et al.), 4,927,408 (Haak et al.) and 5,084,008 (Phipps) , the disclosures of which are hereby incorporated by reference, for delivering a drug or medicine transdermally through iontophoresis, basically consist of two electrodes, i.e., an anode and a cathode. Usually, electric current is driven from an external supply into the skin at the anode, and back out at the cathode. Accordingly, there has been considerable interest in iontophoresis to perform delivery of drugs for a variety of purposes. However, several disadvantages and limitations have been associated with the disposability and reuse of such devices, including cost restraints. For example, as a result of the energy needs, conventional silver oxide and alkaline batteries of the size and cost required do not provide sufficient energy for multiple uses of the system, and lithium batteries, while able to provide sufficient energy, are presently cost prohibitive for use in a single use and/or disposable device. In addition, several disadvantages and limitations have been associated with the flexibility of the device, especially in situations where the device is worn for extended periods of time. For example, as a result prolonged use of the such devices, e.g., over a 24 hour period, they were prone to peeling and uneven distribution of current over the applied area. In addition, the bulkiness of such devices made them cumbersome and noticeable. Thus, there has been a need for an iontophoretic drug delivery system that would eliminate the problems and limitations associated with the prior devices discussed above, most significant of the problems being flexibility disposability and reusability at acceptable energy levels. In addition, there has been a need for a device, that could utilize low cost conventional batteries while achieving sufficient energy levels, and that includes a reusable controller, to provide a compact and inconspicuously worn device. SUMMARY OF THE INVENTION In contrast to the prior devices discussed above, it has been found that a iontophoretic drug delivery system particularly suited for single use and/or disposable use, while providing sufficient energy, and which is particularly suited for application to the body, while providing direct contact even during prolonged use, can be constructed in accordance with the present invention. In addition, the controller for the system of the present invention can be reused to further reduce costs. The iontophoretic drug delivery system of the present invention for delivering at least one active agent to an applied area of a patient, such as the skin, mucous membrane and the like, includes housing means for containing first power means for supplying a high rate of current and sufficient energy to drive the active agent into the patient, electrode assembly means including at least two electrodes for driving the at least one active agent into the applied area of the patient along electrical field lines generated by the electrical current, a first rpservoir situated in electrical communication with a first one of the electrodes and the first reservoir containing the at least one active agent to be delivered to the applied area of the patient, and a second reservoir situated in electrical communication with a second one of the electrodes and the second reservoir, and controller means being removably engageable with the housing means for controlling and monitoring the electrical energy delivered during operation so that the at least one active agent is delivered to the applied area of the patient proximate the first reservoir, whereby upon delivery of the active agent, the controller means and the housing means may be disengaged for reuse of the controller and for disposal of the housing means. In the preferred embodiment of the iontophoretic drug delivery system, the controller means includes a second power means having a high current density for powering the controller means. Also, the at least one active agent includes a local anesthetic and a vasoconstrictor, with the local anesthetic being Lidocaine and the vasoconstrictor being Epinephrine. In addition, the controller means further includes timing means for controlling the amount of electrical current delivered and the first power means is selected from the group including silver oxide batteries, alkaline batteries, zinc air batteries and the like, and the second power means is selected from the group including lithium batteries and the like. In an alternative embodiment, the iontophoretic drug delivery system for delivering at least one active agent to an applied area of a patient, such as the skin, mucous membrane and the like, includes a single use patch including first power means for supplying a high rate of current and sufficient energy to drive the medicament into the patient, electrode assembly means situated within the disposable patch including at least two electrodes for driving the at least one active agent into the applied area of the patient along electrical field lines generated by the electrical current, a first reservoir situated in electrical communication with a first one of the electrodes and the first reservoir containing the at least one active agent to be delivered to the applied area of the patient, a second reservoir situated in electrical communication with a second one of the electrodes and the second reservoir, and reusable controller means being removably engageable with the patch and including a second power means having a high current density for powering the controller means to provide sufficient energy for controlling and monitoring the electrical energy delivered during operation so that the at least one active agent is delivered to the applied area of the patient proximate the first reservoir, whereby upon delivery of the active agent, the controller means and the patch may be disengaged for reuse of the controller and for disposal of the patch. In an alternative embodiment of the present invention, the iontophoretic drug delivery system for delivering at least one active agent to an applied area of a patient, such as the skin, mucous membrane and the like, includes housing means having two or more electrically interconnected pods for containing electrode assembly means including at least two electrodes for driving the at least one active agent into the applied area of the patient along electrical field lines generated by the electrical current, a first reservoir situated in electrical communication with a first one of the electrodes and the first reservoir containing the at least one active agent to be delivered to the applied area of the patient, and a second reservoir situated in electrical communication with a second one of the electrodes and the second reservoir, with at least one of the pods for containing power means for supplying sufficient energy to drive the medicament into the patient, and controller means contained in one of the pods for controlling and monitoring the electrical energy delivered during operation so that the at least one active agent is delivered to the applied area of the patient proximate the first reservoir, whereby the housing conforms to the contours of the applied area. In the preferred embodiment of the system, the pods are interconnected by a flexible web. In addition, the housing means includes an upper portion, a lower portion and an intermediate portion, with the intermediate portion including at least one tab for electrical interconnection with the power means. A preferred embodiment of the iontophoretic drug delivery system, as well as other embodiments, objects, features and advantages of this invention, will be apparent from the following detailed description, which is illustrated in the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a perspective view of the iontophoretic system of the present invention; Figure 2 is a plan view of the iontophoretic system illustrated in Figure 1; Figure 3 is a partly exploded view of the iontophoretic system illustrated in Figure 1 showing connection/disconnection of the controller; and Figure 4 is a perspective view of an alternative embodiment of the iontophoretic system of the present invention. Figure 5 is an exploded view of the iontophoretic system illustrated in Figure 1; Figure 6 is a cross-sectional view of the iontophoretic system illustrated in Figure 1 taken along lines 6-6; and Figure 7 is a partly exploded view of an alternative embodiment of the iontophoretic system of the present invention utilizing a reusable controller. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT The iontophoretic drug delivery system of the present invention is illustrated in Figures 1-7, with the device generally designated 10. Referring now to Figures 1 and 2 , the device 10 of the preferred embodiment of the present invention includes a housing 12, a controller 14 having an electronic array 15 (Figure 5) , a controller power source 16, a drug delivery power source 18 electrically connected to an electrode assembly 20 having two or more electrodes for establishing an electric field between the electrodes for use in delivering at least one active agent iontophoretically to an applied area of the patient. It should be appreciated that the electrodes may be combined in the electrode assembly 20 or separately provided as is well known in the art. In addition, the housing 12 may include a drug filled patch 22, by integrally forming the two. Referring to Figures 1, 2 and 4, the housing 12 includes at least two pods, and preferably three pods 24, 26, 28 as illustrated in Figures 1 and 2, with the electrode assembly 20 divided or otherwise separated into two portions, the first portion 30 includes an electrode 32 and a reservoir 34, with the reservoir 34 being situated adjacent to and in electrical communication with the electrode 32. The second portion 36 also includes an electrode 38 and a reservoir 40, with the reservoir 40 being situated adjacent to and in electrical communication with the electrode 38. In the preferred embodiment, the pod 24 includes the drug delivery power source 18, such as, for example, a silver oxide, alkaline or zinc air battery, connected in a circuit with electrodes 32 and 38. The other pod 28, removably contains the controller 14 and the controller power source 16, such as, for example a small lithium battery. In this way, the lithium battery 16 has a long shelf life and has a high current density but it is not necessarily capable of high current discharge. On the other hand, since the patch is only used once, i.e., to apply a "single shot," the need for a lithium battery to supply the drug delivering current is eliminated, with a resulting reduction in cost. Also, since the silver oxide, alkaline or zinc air battery is provided in the housing 12, the housing 12, along with the patch, can be disposed of after a single use. While, the controller 14 can be disengaged or otherwise disconnected from the housing, as illustrated in Figure 3, and reused, along with the corresponding lithium battery. The controller 14 and the battery 16 are connected in a circuit, with the controller 14 preferably including an electronic array, such as for example, a microprocessor, a dc/dc converter to increase the battery supply to approximately 30 volts, a current regulator which is controlled by the microprocessor and a timer for monitoring the period of time the electrical current flows in a particular direction and/or the amount of current applied. In addition, current flowing through the reservoirs 34, 40 and the applied area can be controlled with a compliance voltage sufficient to account for variations in skin impedance and losses within the reservoirs. In the preferred embodiment, the pod 28 houses the controller and includes the electronic array 15 as well as the power source 16 connected in a circuit with electrodes 32 and 38. It should be appreciated that the particular electrode assembly and the electronic array are not essential to the present invention and may include, for example, those disclosed in co-pending U.S. Application S.N. 08/129,887, filed September 30, 1993, the disclosure of which is hereby incorporated by reference in its entirety. In the preferred embodiment, the controller 14 includes means for controlling the level of current to be applied over time and also for varying the current. Accordingly, the device 10 can be utilized, for example, to vary the current I, during time period T.,, current I 2 during time period T 2 , current l 3 during time period T 3 , current I 4 during time period T 4 , and current I 5 during time period T 5 and additional currents and time intervals as needed. Also, the controller may be adapted to include means for controlling the voltage V or the power I-V as well. As is well known within the field, the device can be situated on the area of the patient to which the active agent is to be applied (the applied area) such as the skin and a voltage impressed across the electrodes 32 or 34 of the electrode assembly 20 to cause electrical current to flow through the skin of the patient to drive or otherwise transport the ionic active agent into the skin and the tissue to be absorbed by the body of the patient. The electric field lines are sufficiently long, however, so that the active agent is transported to the desired depth within the skin, and possibly to the vasculature, to provide the desired effect, e.g., anesthetic, therapeutic or diagnostic. It should also be appreciated that the device of the present invention can be applied to other areas of the body such as mucous membranes depending upon the desired therapy and drugs to be delivered. An alternative embodiment of the system 50 is illustrated in Figure 4 showing two pods 52 and 54, with the power source 56 being contained with pod 52 and the controller 58 being interconnectable with pod 54. Referring now to Figures 5-7, an additional feature of the present invention will now be described. As illustrated in Figure 5, the housing 12 includes an upper portion 60, a base or lower portion 62, and a intermediate portion 64. As previously mentioned, the housing 12 includes a number of pods, and preferably three pods 24, 26, 28 interconnected by a web 66 containing the circuit connecting the three pods. In the preferred embodiment, the intermediate portion 64 includes one or more locking tabs 68, 70 for engaging the power source, which may be split equally between the pods 24, 26 leaving only the electronic array, including logic circuit, in the other pod 28. Likewise, the power source may be incorporated within the electronic array. Also, the electrode assembly 20 is divided or otherwise separated into two portions, with the first pod 24 including an electrode 32 and a reservoir 34, with the reservoir 34 being situated adjacent to and in electrical communication with the electrode 32 as illustrated in Figure 6. The second pod 28 also includes an electrode 38 and a reservoir 40, with the reservoir 40 being situated adjacent to and in electrical communication with the electrode 38. In this way, a lower surface of the intermediate portion 64 may include an electrode layer as disclosed, for example, in U.S. Patent Application S.N. 08/012,168, filed February 2, 1993, the disclosure of which is hereby incorporated by reference in its entirety. In one embodiment of the invention, Lidocaine (a local anesthetic) and Epinephrine (a vasoconstrictor) are utilized such that the device can be used for anesthetizing the applied area to minimize sensation from the insertion of a needle or the like. In the preferred embodiment, the first reservoir 34 holds at least one active agent, formulation, medication or drug 42, preferably in an ionized or ionizable form, to be delivered iontophoretically to the applied area of the patient. However, electrodes 32 and 38 may include an electrolyte, with the particular electrolyte not being essential to the present invention and merely a matter of choice. However, in this embodiment the electrolyte may include sodium chloride in an aqueous solution, matrix or the like. In situations where a polymer material or another material is used, it may also act as an adhesive, eliminating the need in prior devices for an adhesive layer or the like. However, it should be apprecaited that in certain clinical applicantions it may be desireable to provide an adhesvie layer under the web 66 in which case the pods can still be in planes that rotate slightly with respect to one another. Likewise, it may be desireable to forgo the adhesive under the web so that the planes can rotate and also flex in the distance between the centers of the pods to accommodate the skin as it stretches or muscles flex. Also, some elasticity or excess length can be incorporated. In this way, increased reliability of skin contact is achieved and maintained by the patient when wearing the device 10, especially for prolonged periods of time. The active agent can have either a negative charge or a positive charge, but the active electrode must also be negatively or positively charged, respectively. Accordingly, where the active agent contained in the reservoir 34 or 40 is positively charged, the electrical current flows from the first electrode 32 to the second electrode 38, and the first electrode 32 acts as the active electrode and the second electrode 38 acts as the return electrode, with the drug being delivered to the applied area of the skin approximate the first electrode 32 and the first reservoir 34. In the preferred embodiment, the drug reservoir 34 includes the medicament 42 for delivery, which may contain, for example, either Alfentanil, Baclofen, Beclomethasone, Betamethasone, Buspirone, Cromolyn sodium, Bromocriptine, Calcitonin, Diclofenac, Diltiaze , Doxazosin, Droperidol, Encainide, Fentanyl, Granisetron, Haloperidol, Hydrocortisone, Indomethacin, Insulin, Isosorbide dinitrate, Ketoprofen, Ketorolac, Lidocaine, Lisinopril, LMW heparin, Melatonin, Methotrexate, Metoclopramide, Miconazole, Midazolam, Nicardipine, Oxybutynin, PGE 1, Piroxicam, Pramipexole, Prazosin, Scopolamine, Seglitide, Sufentanil, Terbutaline, Testosterone, Tetracaine, Tropisetron, Verapamil, Warfarin, Zacropride and Zatosetron, including derivatives, analogs and the like, which varying in duration for delivery from minutes to hours. In this way, the device can be used for delivering the medicament to the applied area for a short period of time or for extended periods of time. In addition, it should be appreciated that the dose of the medication can be varied depending upon the substance used. Active agent, drug, formulation, medication, medicament and active compound have been used herein to mean any pharmaceutical agent, such as therapeutic compounds, diagnostic agents, anesthetic agents and the like. Referring now to Figure 7, an embodiment of the device 10 is illustrated in which the housing 12 includes three pods 24, 26 and 28, with the electronic array being contained in a controller 14 removably engageable by a sliding action in a receiving portion 21 formed in the housing. Likewise, referring again to Figure 4, another embodiment of the device 10 is illustrated in which the housing includes two pods 52 and 54, with the electronic array being contained in a controller 14 removably engageable by a sliding action in a receiving portion 21 formed in the housing similar to that shown in Figure 3. Accordingly, it should be appreciated that the pods can be arranged radially as illustrated in Figures 1-7 or some other orientation such as linearly, e.g., two or three in a row to accommodate the specific requirements of the desired body location on which the device is to be applied. The operation of the system of the present invention will now be explained with reference to Figures 1-7, specifically that the device 10 including the various pods 24, 26, 28 interconnected by the flexible web 66 allows the device to be applied to the body with each of the pods not being influenced by the plane of attachment of the other pods. Thus, if the device were to be applied on a spherical surface, each pod would only have to be flexible enough to give good contact under itself. In addition, while the device has been described in connection with iontophoresis, it should be appreciated that it may be used in connection with other principles of active introduction, i.e., motive forces, such as electrophoresis which includes the movement of particles in an electric field toward one or other electric pole, anode, or cathode and electro-osmosis which includes the transport of uncharged compounds due to the bulk flow of water induced by an electric field. Also, it should be appreciated that the patient may include humans as well as animals. While the preferred embodiments of the present invention have been described so as to enable one skilled in the art to practice the device of the present invention, it is to be understood that variations and modifications may be employed without departing from the concept and intent of the present invention as defined in the following claims. The preceding description is intended to be exemplary and should not be used to limit the scope of the invention. The scope of the invention should be determined only by reference to the following claims.

Claims: WHAT IS CLAIMED IS; 1. An iontophoretic drug delivery system for delivering at least one active agent to an applied area of a patient, such as the skin, mucous membrane and the like, comprising: housing means for containing first power means for supplying a high rate of current and sufficient energy to drive the active agent into the patient, electrode assembly means including at least two electrodes for driving the at least one active agent into the applied area of the patient along electrical field lines generated by said electrical current, a first reservoir situated in electrical communication with a first one of the electrodes and said first reservoir containing said at least one active agent to be delivered to the applied area of the patient, and a second reservoir situated in electrical communication with a second one of said electrodes and said second reservoir; and controller means being removably engageable with said housing means for controlling and monitoring the electrical energy delivered during operation so that said at least one active agent is delivered to the applied area of the patient approximate said first reservoir, whereby upon delivery of the active agent, said controller means and said housing means may be disengaged for reuse of said controller and for disposal of said housing means. 2. An iontophoretic drug delivery system as defined in claim 1, wherein said controller means includes a second power means having a high current density for powering the controller means. 3. An iontophoretic drug delivery system as defined in claim 1, wherein said at least one active agent includes a local anesthetic and a vasoconstrictor. 4. A iontophoretic drug delivery system as defined in claim 1, wherein said controller means further includes timing means for controlling the amount of electrical current delivered. 5. An iontophoretic drug delivery system for delivering at least one active agent to an applied area of a patient, such as the skin, mucous membrane and the like, comprising: a single use patch including first power means for supplying a high rate of current and sufficient energy to drive the medicament into the patient; electrode assembly means situated within said disposable patch including at least two electrodes for driving the at least one active agent into the applied area of the patient along electrical field lines generated by said electrical current; a first reservoir situated in electrical communication with a first one of the electrodes and said first reservoir containing said at least one active agent to be delivered to the applied area of the patient; a second reservoir situated in electrical communication with a second one of said electrodes and said second reservoir; and reusable controller means being removably engageably with said patch and including a second power means having a high current density for powering the controller means to provide sufficient energy for controlling and monitoring the electrical energy delivered during operation so that said at least one active agent is delivered to the applied area of the patient approximate said first reservoir, whereby upon delivery of the active agent, said controller means and said patch may be disengaged for reuse of said controller and for disposal of said patch. 6. An iontophoretic drug delivery system for delivering at least one active agent to an applied area of a patient, such as the skin, mucous membrane and the like, comprising: housing means having two or more electrically interconnected pods for containing electrode assembly means, a first reservoir and a second reservoir, with at least one of said pods for containing power means for supplying sufficient energy to drive the medicament into the patient; said electrode assembly means including at least two electrodes for driving the at least one active agent into the applied area of the patient along electrical field lines generated by said electrical current; said first reservoir situated in electrical communication with a first one of the electrodes and said first reservoir containing said at least one active agent to be delivered to the applied area of the patient; said second reservoir situated in electrical communication with a second one of said electrodes and said second reservoir; and controller means contained in one of said pods for controlling and monitoring the electrical energy delivered during operation so that said at least one active agent is delivered to the applied area of the patient approximate said first reservoir, whereby said housing conforms to the contours of the applied area. 7. An iontophoretic drug delivery system as defined in claim 6, wherein said pods are interconnected by a flexible web. 8. An iontophoretic drug delivery system as defined in claim 7, wherein said housing means includes an upper portion, a lower portion and an intermediate portion. 9. An iontophoretic drug delivery system as defined in claim 6, wherein intermediate portion includes at least one tab for electrical interconnection with said power means. 10. An iontophoretic drug delivery system for delivering at least one active agent to an applied area of a patient, such as the skin, mucous membrane and the like, comprising: housing having a first pod, a second pod and a third pod, with said pods being electrically interconnected by a flexible web; electrode assembly means situated including at least two electrodes for driving the at least one active agent into the applied area of the patient along electrical field lines generated by said electrical current; said first pod including one of said electrodes and a first reservoir situated in electrical communication with said one of the electrodes and said first reservoir containing said at least one active agent to be delivered to the applied area of the patient; said second pod including the other one of said electrodes and a second reservoir situated in electrical communication with said second one of said electrodes; one of said pods including power means for supplying electrical current and sufficient energy to drive said at least one active agent into the patient; and said third pod including controller means for controlling and monitoring the electrical energy delivered by said power means during operation so that said at least one active agent is delivered to the applied area of the patient approximate said first reservoir, whereby said housing conforms to the contours of the applied area. 11. A iontophoretic drug delivery system as defined in claim 10, wherein said third pod includes interconnection means for releasably engaging said controller means.

Inventors: FLOWER RONALD J, MCARTHUR WILLIAM ALLAN, STROPKAY SCOTT EDWARD, TANNER MARC WALTER, FLOWER, RONALD, J., MCARTHUR, WILLIAM, ALLAN, STROPKAY, SCOTT, EDWARD, TANNER, MARC, WALTER
Applicants: BECTON DICKINSON CO, BECTON DICKINSON AND COMPANY
Application year: 1995
Main classification: A61N1
IPC codes: A61N1