WO2000066216A1 - Apparatus for dosaging an active ingredient and for investigating the dosage - Google Patents
Apparatus for dosaging an active ingredient and for investigating the dosage Download PDFInfo
- Publication number
- WO2000066216A1 WO2000066216A1 PCT/FI2000/000263 FI0000263W WO0066216A1 WO 2000066216 A1 WO2000066216 A1 WO 2000066216A1 FI 0000263 W FI0000263 W FI 0000263W WO 0066216 A1 WO0066216 A1 WO 0066216A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- membrane
- section
- chamber
- connection
- active agent
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/20—Applying electric currents by contact electrodes continuous direct currents
- A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
Definitions
- the invention relates to a device based on iontophoresis and intended for transder- mal dosing of an active agent.
- the invention also relates to an iontophoretic device intended for the study of the dosing, i.e. release, of an active agent.
- Transdermal dosing of drugs is an established administering method for many drugs.
- the long-term, even and controlled concentration of a drug in the body, provided by the transdermal administering method, is commonly considered an advan- tage of the method.
- the side effects of a drug can be reduced and a smaller amount of a drug can be used.
- the metabolism caused by the liver and the intestinal wall is avoided when drugs are administered trans- dermally.
- Transdermal dosing involves the problem of poor permeation of drugs through the skin, in particular with an increasing molecular size of the drug.
- One method for solving this problem is to promote the transport of the drug through the skin by means of electric current. This is iontophoresis, which has the crucial advantage that the permeation of the drug through the skin is determined primarily by the electric current and the physicochemical parameters of the drug.
- the object is to provide a study device which simulates transdermal in vivo dosing, and by means of which it is possible to investigate the permeation parameters suited for each given drug and thereby to tailor drug-specifically optimal dosing devices.
- Figure 1 depicts a transdermal dosing device according to the invention
- Figure 2 depicts a device according to the invention, intended for the study of the release of an active agent
- Figure 3 depicts, as a function of time, the drug amount delivered by a device according to the invention.
- Figure 4 depicts, as a function of time, the drug amount delivered by a device according to the invention, for two electrolyte concentrations prevailing in the ion- exchange space.
- Figure 1 depicts a device according to the invention, based on iontophoresis and intended for transdermal dosing of an active agent.
- the device comprises a pair of electrodes 1 1 , 12 and a direct-current source (not shown in the figure) in connection with the electrodes, as well as two chambers 13 and 14, which are insulated from each other by an insulator 17, which in this option also serves as the supporting structure of the chambers.
- Each chamber has a porous membrane 15 respectively 16 on the side facing the skin of an individual.
- the first chamber 13 is divided into two sections 13a and 13b in such a manner that the first section 13a is in connection with the electrode 1 1 and the second section 13b is in connection with the membrane 15 coming into contact with the skin 20 of an individual.
- the first section 13a contains an electrolyte and the second section 13b contains an ionic active a ⁇ ent bound to an ion exchanger therein.
- the negatively or positively charged ion-exchange groups may be attached to an ion-exchange resin or some other matrix. Preferably they are grafted to a fiber. If the drug to be dosed is cationic, negatively charged ion-exchange groups, i.e. a cation exchanger, is used.
- the membrane 18 which separates the sections 13a and 13b of the chamber 13 from each other is, depending on whether the drug to be dosed is cationic or anionic, a membrane selectively permeable either to cations or to anions.
- membranes 15 and 16 coming against the patient's skin 20 may be ordinary porous membranes, it is, however, preferable that, depending on whether the drug to be dosed is cationic or anionic, both are membranes selectively perme- able either to cations or to anions.
- the electrolyte in the first section 13a of the chamber 13 may be in solution form.
- the electrolyte may be in dry form, in which case the electrolyte can be activated by means of an activator (such as water) added into the section 13a.
- an activator such as water
- Electrode 1 1 is an anode and 12 a cathode.
- the electrodes are, for example, Ag, respectively AgCl.
- section 13a which contains an electrolyte, e.g. NaCl, there is caused by an electrode reaction a selective transport of the cation through the cation-selective membrane 18 to section 13b, in which the cationic drug is bound to an ion exchanger.
- Section 13b also contains an electrolyte (NaCl).
- Section 13a of the chamber must contain a sufficiently large amount of salt in order to provide a sufficient cation flow, and in some cases a sufficient electrode reaction, for a sufficiently long time. The required amount of electrolyte can be calculated on the basis of Faraday's law.
- the anode is silver and the electrolyte is NaCl, silver chloride is formed through the electrode reaction. In this case the electrode reaction is
- the anion in the anode space i.e. in chamber section 13a
- the electrode reaction may be, for example,
- the cation in this example case Na+
- chamber section 13b i.e. the ion-exchange space
- quantitatively almost the same number of cations is transported from this space through the porous membrane 15 which is selectively permeable to cations, and thereafter through the skin 20.
- the membrane 15 is a merely microporous membrane and not a cation-selective membrane, a portion of the cation flow is lost for the benefit of anions.
- the salt concentration in the ion-exchange space (section 13b) tends to rise considerably more than when a cation-selective membrane is used.
- the drug flow through the skin may weaken somewhat.
- the change can be observed and, when necessary, be corrected by adjusting the electric current (the power of the direct-current source is preferably controllable).
- the ions transported from the device through the skin 20 into the body are Na + and the drug cation is L + . If the membrane 15 used is a merely microporous membrane, some Cl " ions are also transported from the body through the skin.
- the quantity of L + and Na + ions transported into the body depends on the salt concentration in the ion-exchange space (section 13b), on the distribution constant between the drug and the salt, typical of the ion exchanger, and on the electric mobilities of the salt cation and the drug cation. This arrangement en- ables the drug to be dosed precisely, since the flow of drug cations through the skin can be determined by control of the electric current.
- the cathode 12 can be an AgCl electrode or a gas-generating electrode in the same manner as in the anode space. In this case it is also necessary to attend to buffering, since the electrode reaction in most cases develops hydroxyl ions.
- the electrodes are exchanged so that 1 1 is the cathode and 12 is the anode.
- Membrane 18 must be a membrane selectively permeable to anions.
- Membranes 15 and 16 must also be membranes selectively perme- able to anions, unless they are merely microporous membranes.
- the ion exchanger in the space 13b must be an anion exchanger.
- Figure 2 shows a device according to the invention, suitable for the study of drug release.
- the device is structurally the same as the dosing device of Figure 1, except that the skin 20 of an individual has been replaced with human or animal skin or a synthetic membrane, and that the chamber 14 serves as a sample-taking container.
- the container 14 contains a salt solution, for example, a physiologic salt solution or a suitable NaCl solution.
- a salt solution for example, a physiologic salt solution or a suitable NaCl solution.
- Metoprolol which is a cationic drug
- ion exchanger S-102 (Smoptech)
- the ion exchanger space 13b contained 0.15 M NaCl.
- the anode space 13a contained 0.5 M NaCl and the cathode chamber 14 contained 30 ml of 0.15 M NaCl.
- the membrane 15 was a porous membrane in which the pore diameter was 5 ⁇ m.
- the membrane was cation-selective (PVDF-PAA (4 %)).
- the cation-exchange membrane 18 was Nafion, in Na + form.
- the quantity of metoprolol accumulated in the chamber 14 was measured as a function of time.
- the cumulated metoprolol amount m as a function of time t is presented in Figure 3; m is the amount of the substance.
- the correlation of the straight line is 0.9994.
- Example 2 The test was carried out as in Example 1 , except that the electrolyte concentration in the ion-exchanger space 13b was 0.015 M NaCl and in the anode space 13a 0.15 M NaCl.
- Figure 4 shows as a function of time the cumulative metoprolol amounts accumulated in the cathode chamber 14 in both of the tests 1 and 2. It is seen that a decrease in the electrolyte concentration in the ion-exchange space increases the drug ion flow.
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU35635/00A AU3563500A (en) | 1999-04-29 | 2000-03-29 | Apparatus for dosaging an active ingredient and for investigating the dosage |
CA002368757A CA2368757A1 (en) | 1999-04-29 | 2000-03-29 | Apparatus for dosaging an active ingredient and for investigating the dosage |
EP00914231A EP1173251A1 (en) | 1999-04-29 | 2000-03-29 | Apparatus for dosaging an active ingredient and for investigating the dosage |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI990977A FI107372B (fi) | 1999-04-29 | 1999-04-29 | Laite vaikuttavan aineen annosteluun ja annostelun tutkimukseen |
FI990977 | 1999-04-29 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000066216A1 true WO2000066216A1 (en) | 2000-11-09 |
Family
ID=8554556
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FI2000/000263 WO2000066216A1 (en) | 1999-04-29 | 2000-03-29 | Apparatus for dosaging an active ingredient and for investigating the dosage |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1173251A1 (zh) |
AU (1) | AU3563500A (zh) |
CA (1) | CA2368757A1 (zh) |
FI (1) | FI107372B (zh) |
WO (1) | WO2000066216A1 (zh) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007038028A1 (en) * | 2005-09-28 | 2007-04-05 | Tti Ellebeau, Inc. | Iontophoresis apparatus and method to deliver active agents to biological interfaces |
WO2007041322A2 (en) * | 2005-09-30 | 2007-04-12 | Tti Ellebeau, Inc. | Iontophoretic delivery of active agents conjugated to nanoparticles |
EP1818076A1 (en) * | 2004-11-30 | 2007-08-15 | Transcutaneous Technologies Inc. | Iontophoresis device |
EP1941928A1 (en) * | 2005-09-30 | 2008-07-09 | Tti Ellebeau, Inc. | Electrode structure for iontophoresis used to administer drug enclosed in nanoparticle and iontophoresis device making use of the same |
WO2014027136A1 (en) * | 2012-08-13 | 2014-02-20 | Novagent Oy | Iontophoretic device for dosaging of an active ingredient |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4692462A (en) * | 1985-03-18 | 1987-09-08 | Menley & James Laboratories, Ltd. | Compositions and method of controlling transdermal penetration of topical and systemic agents |
US4731049A (en) * | 1987-01-30 | 1988-03-15 | Ionics, Incorporated | Cell for electrically controlled transdermal drug delivery |
EP0411146A1 (en) * | 1989-02-06 | 1991-02-06 | Hisamitsu Pharmaceutical Co., Inc. | Interface for iontophoresis |
US5250022A (en) * | 1990-09-25 | 1993-10-05 | Rutgers, The State University Of New Jersey | Iontotherapeutic devices, reservoir electrode devices therefore, process and unit dose |
US5362308A (en) * | 1990-09-25 | 1994-11-08 | Rutgers, The State University Of New Jersey | Disposable dosage unit for iontophoresis-facilitated transdermal delivery, related devices and processes |
WO1997027844A1 (en) * | 1996-01-30 | 1997-08-07 | Novagent Oy | Composition for transdermal delivery of drugs |
WO1997047353A1 (en) * | 1996-06-13 | 1997-12-18 | Novagent Oy | Composition and system for iontophoretic transdermal delivery of drugs |
-
1999
- 1999-04-29 FI FI990977A patent/FI107372B/fi not_active IP Right Cessation
-
2000
- 2000-03-29 EP EP00914231A patent/EP1173251A1/en not_active Withdrawn
- 2000-03-29 WO PCT/FI2000/000263 patent/WO2000066216A1/en not_active Application Discontinuation
- 2000-03-29 AU AU35635/00A patent/AU3563500A/en not_active Abandoned
- 2000-03-29 CA CA002368757A patent/CA2368757A1/en not_active Abandoned
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4692462A (en) * | 1985-03-18 | 1987-09-08 | Menley & James Laboratories, Ltd. | Compositions and method of controlling transdermal penetration of topical and systemic agents |
US4731049A (en) * | 1987-01-30 | 1988-03-15 | Ionics, Incorporated | Cell for electrically controlled transdermal drug delivery |
EP0411146A1 (en) * | 1989-02-06 | 1991-02-06 | Hisamitsu Pharmaceutical Co., Inc. | Interface for iontophoresis |
US5250022A (en) * | 1990-09-25 | 1993-10-05 | Rutgers, The State University Of New Jersey | Iontotherapeutic devices, reservoir electrode devices therefore, process and unit dose |
US5362308A (en) * | 1990-09-25 | 1994-11-08 | Rutgers, The State University Of New Jersey | Disposable dosage unit for iontophoresis-facilitated transdermal delivery, related devices and processes |
WO1997027844A1 (en) * | 1996-01-30 | 1997-08-07 | Novagent Oy | Composition for transdermal delivery of drugs |
WO1997047353A1 (en) * | 1996-06-13 | 1997-12-18 | Novagent Oy | Composition and system for iontophoretic transdermal delivery of drugs |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1818076A1 (en) * | 2004-11-30 | 2007-08-15 | Transcutaneous Technologies Inc. | Iontophoresis device |
EP1818076A4 (en) * | 2004-11-30 | 2009-03-04 | Tti Ellebeau Inc | Iontophoresis device |
WO2007038028A1 (en) * | 2005-09-28 | 2007-04-05 | Tti Ellebeau, Inc. | Iontophoresis apparatus and method to deliver active agents to biological interfaces |
WO2007041322A2 (en) * | 2005-09-30 | 2007-04-12 | Tti Ellebeau, Inc. | Iontophoretic delivery of active agents conjugated to nanoparticles |
WO2007041322A3 (en) * | 2005-09-30 | 2007-06-07 | Transcutaneous Tech Inc | Iontophoretic delivery of active agents conjugated to nanoparticles |
EP1941928A1 (en) * | 2005-09-30 | 2008-07-09 | Tti Ellebeau, Inc. | Electrode structure for iontophoresis used to administer drug enclosed in nanoparticle and iontophoresis device making use of the same |
EP1941928A4 (en) * | 2005-09-30 | 2008-12-24 | Tti Ellebeau Inc | ELECTRODE STRUCTURE FOR IONTOPHORESIS FOR USE IN ADMINISTERING A MEDICAMENT CONTAINED IN A MICROPARTICLE AND IONTOPHORESIS DEVICE USING THE STRUCTURE |
WO2014027136A1 (en) * | 2012-08-13 | 2014-02-20 | Novagent Oy | Iontophoretic device for dosaging of an active ingredient |
EP2882490A4 (en) * | 2012-08-13 | 2016-01-27 | Novagent Oy | IOPOPHORESIS DEVICE FOR DOSING AN ACTIVE SUBSTANCE |
Also Published As
Publication number | Publication date |
---|---|
AU3563500A (en) | 2000-11-17 |
FI990977A0 (fi) | 1999-04-29 |
FI990977A (fi) | 2000-10-30 |
CA2368757A1 (en) | 2000-11-09 |
EP1173251A1 (en) | 2002-01-23 |
FI107372B (fi) | 2001-07-31 |
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