Iontotherapeutic devices, reservoir electrode devices therefore, process and unit dose

• US 5,250,022 A
• Filed: 09/25/1990
• Issued: 10/05/1993
• Est. Priority Date: 09/25/1990
• Status: Expired due to Term

• Current Assignee: Rutgers University
• Original Assignee: Rutgers University
• Inventors: Banga, Ajay K., Chien, Yie W.
• Primary Examiner(s): Pellegrino, Stephen C.
• Assistant Examiner(s): Rafa, Michael
• Application Number:
  US07/587,406
• Time in Patent Office: 1,106 Days
• Field of Search: 604/20, 128/798, 128/802, 128/803
• US Class Current: 604/20
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61N 1/044 Shape of the electrode
• CPC Class Codes: A61N 1/0444 Membrane
• CPC Class Codes: A61N 1/0448 Drug reservoir

Abstract

Provided are reservoir electrodes for iontotherapeutic devices which have two chambers; the first chamber is electrically connected to the iontotherapeutic device and is designed to contain electrolytic solution and the second chamber has ionized pharmaceutical dissolved in electrolytic solution. The two chambers are separated by a permselective membrane. The first chamber has means to inhibit increase in ionic content caused by the operation of the iontotherapeutic device. Also provided are unit dose forms adapted for insertion into the reservoir electrodes. The dose unit forms are made of crosslinked polymer and contain ionizable pharmaceutical which is released for absorption during operation of the iontotherapeutic process. Also provided are novel iontotherapeutic devices and processes.

Claims

1. A pharmaceutical reservoir electrode for use in iontotherapeutic delivery of a pharmaceutical which is ionized and is contained therein, comprising:

a) a housing for said electrode;

b) a first chamber which contains an electrolytic solution to permit said iontotherapeutic delivery to take place and having present therein ion exchange granules which inhibit increased ionic content through ion generation in the electrode in the first chamber as the iontotherapeutic process takes place;

c) an electrical terminus to contact electrically the electrolytic solution contained in said first chamber;

d) a second chamber for receiving a unit dose of said ionized pharmaceutical, and

e) a permselective membrane separating said first and second chambers, said membrane characterized by having pores with sufficiently low permeability to inhibit substantial passage of said ionized pharmaceutical present in said second chamber into said first chamber, said permselective membrane being substantially free of ion exchange sites.

2. An electrode of claim 1 wherein the unit dose is a crosslinked hydrophilic polymer unit dose adapted to fit into and be securely held in the second chamber, which chamber has an open mouth, said unit dose capable of retaining an aqueous solution of an ionized pharmaceutical and releasing said pharmaceutical by iontotherapeutic process.

3. An electrode of claim 2 wherein said unit dose is a crosslinked acrylamide polymer.

4. An electrode of claim 2 wherein said unit dose is a crosslinked p-HEMA polymer.

5. An electrode of claim 2 wherein said unit dose contains an ionized peptide pharmaceutical.

6. An electrode of claim 5 wherein the polymer of the unit dose is selected from the group consisting of acrylamide polymers and p-HEMA polymers.

7. An electrode of claim 1 wherein the pH of the aqueous solution of said ionized pharmaceutical is at least 1.5 pH units below or above the pKa or isoelectric point, if said ionized pharmaceutical is a peptide.

8. An electrode of claim 7 wherein said pharmaceutical is insulin.

9. An electrode of claim 1 wherein said first chamber is filled with a crosslinked hydrophilic polymer disc which is conductive, filled with an electrolytic buffer and has dispersed therein ion exchange resin granules capable of inhibiting increase of ionic content during iontotherapy.

10. An electrode of claim 9 wherein the unit dose is a crosslinked hydrophilic polymer unit dose capable of retaining an aqueous solution of an ionized pharmaceutical and releasing said pharmaceutical by iontotherapeutic process.

11. An iontotherapeutic device comprising a pharmaceutical reservoir electrode as defined in claim 1.

12. A device of claim 11 wherein said device is capable of providing a periodic DC current having a current density of about 0.1 to about 1 mA/cm² of area of contact of the electrode with the skin of the subject being treated.

13. A process for iontotherapeutic administration of an ionized pharmaceutical to a subject desiring such therapy, comprising the steps of:

a) applying to the skin surface of the subject a reservoir electrode as described in claim 1, said reservoir electrode containing an electrolytic solution in the first chamber and containing an ionized pharmaceutical solution in the second chamber;

b) applying to the skin of the subject a second electrode spaced from said first reservoir electrode; and

c) supplying current to the electrode which are electrically connected to cause iontotherapeutic administration of an effective amount of the ionized pharmaceutical to the subject from said first reservoir electrode.

14. A sterile unit dose adapted to be removably inserted into the receiving chamber of a reservoir electrode of a transdermal periodic iontotherapeutic system, said unit dose to be used in electrical contact with intact skin to be iontotherapeutically treated to administer transdermally a systemically effective dose amount of an effective and transdermally absorbable amount of an ionized pharmaceutical;

said unit dose containing a sterile solution of said ionized pharmaceutical dispersed therein having an iontotherapeutically effective and physiologically acceptable pH at least about one pH unit lower or higher than the pKa or isoelectric point of said pharmaceutical;

said unit dose adapted to permit said pharmaceutical to be released upon application to the reservoir electrode of an effective DC current;

said unit dose made of a crosslinked, hydrophilic polymer and being dimensionally stable.

15. A unit dose of claim 14 in which the ionized pharmaceutical is contained and uniformly dispersed in the crosslinked polymer unit dose in which the polymer used in making the unit dose is essentially non-ionic, hydrophilic and essentially compatible with said pharmaceutical and the intact skin to be treated.

16. A unit dose of claim 14 in which the polymer is an acrylamide polymer.

17. A unit dose of claim 14 in which the polymer is a methacrylate type.

18. A unit dose of claim 14 wherein the ionized pharmaceutical is a peptide.

19. A unit dose of claim 18 wherein the pharmaceutical is selected from insulin, vasopressin and calcitonin.

20. A unit dose of claim 18 wherein there is present in said unit dose an effective amount of a proteolytic degradation inhibitor.

21. A unit dose of claim 14 characterized by the water of said aqueous solution of said pharmaceutical has been removed.