CA2405925A1 - Electrolytic cell - Google Patents

Abstract

Electrolytic cells are described. The cells comprise the electrolyte K2HPO4, or a less alkaline phosphate buffer solution, electrodes having a modified composition, or a combination of the electrolyte and a modified composition electrode. The K2HPO4 electrolyte, or less alkaline phosphate buffer solution, and modified electrodes can be used in liquid delivery devices which deliver a liquid agent at a constant rate or a controlled variable rate over a period of time.

Description

IMPROVED ELECTROLYTIC CELL
FIELD OF THE ON
The present invention is directed to an improved electrolytic cell having novel electrolytes and/or novel electrode m~.terials. The electrolytic cell can be used as a gas generator for a drug delivery device.
BACKGROUND OF THE INVENTION
There are many applications requiring the dispensing or delivering of a liquid at a predetermined or precisely controlled rate. One application requiring a particularly precise rate of delivery 1s a system for administering a drug, such as insuliil or morphine. Precise pumps have been devised for this propose. However, such pumps are expensive to produce and maintain, and are inconvenient to refill with the periodic dosage requireulents.
One solution to this problem is to use an electrolytic cell as a gas generator which functiops to dispense a liquid from a device. For example, ~(J_S. Patent No.
5,U62,834 ("the '834 patent', for "Device for Dispensing a Liquid Particularly Useful far pelivering Ivledicameuts at a Predetermined Rate," describes a device fnr dispensing a liquid at a predetermined rate. The device comprises a container for the liquid to be 2o dispensed and a piston assembly movable within the container and dividing the container into two expandable-contracu'ble chambers. The first chamber contains the liquid to be dispensed and the second chaiaber contains pressuri2ed gas which functions to dispense the liquid from the fitsi chamber of the container. The second expandable-contractible chamber includes an electrolytic cell having electrodes and an electrolyte.
Upon energizaiion of the cell, the electrolyte conducts current between the electrodes, triggering the generation of gas.
The electrolytic cell of the '834 patent comprises a pair of electrodes and an elecuolyte capable of generating a gas upon energization of the electrodes.
The gas expands the second chamber which results in displacing a piston, thereby forcing the 3o liguid out from the fast chamber. Examples of useful electrolytes include saline solution ~d other polar solutions or gels which g~~te hydrogen, oXYge~ Tll~'ogen or carbon dioxide. A similar device containing an electrolytic cell is described in U.S.
Patent No.
5,242,406 for "Liq~d Delivery Device Particularly Useful for Delivering Drugs."
Another exatnplc of an electrolytic cell used in a drug delivery device is given in U.S.1'atent No. 5,090,963 for Electrochemically Driven Metering Medicament pispenser:' This patent descn-bes a liquid m&terial dispenser comprising an electrolytic cell capable of generating a gas When energized by a source of electric current. The liquid material dispenser comprises a rigid horsing hang a flexible partitiop forming two comparuneats_ UPoz~ enervation bY a source of electric current, the electrolytic cell in 1o the first compartment generates a gas, thereby expanding the first compartment of the dispenser. This results in contracting the second comparnnent containing the liquid material, thereby dispepsitlg the liquid material. The patent teaches that the electrolyte can be an 8% solution of sodium bicarbonate (NaHC~3) ~ water or a 4% solution of c4pper sulphate (CuSO~ in water.
15 Yet another example of a prior art use of an electrolytic cell in a drug delivery device is given in U.S. Patent No. 5,186,805 ("the 805 patent") for "Electrolytic Dispcusing Device." This patent describes a device similar to that the '834 patent- For this particular adaptation of an electrolytic cell, the electrodes are preferably stainless steel nets or s~~ns. The electrolyte care be a Water solution of various calls or acids, 2o such as baking soda (sodium bicarbonate), caustic soda, magnesium sulphate, Potassium sulphate, sodium sulphate, potassium nitzate, potassium bicarbonate, boric acid, acetic acid, fonuic acid, or carbonic acid. The '845 patent teaches that particularly good results were obtained using an 8% solution of baking soda (s~~ bicarbonate) as an electrolyte.
~ Finally, a liquid material disp~er, in which the liquid is forced from the dispenscr by a gas generated by an electrolyric cell, is described in U.S.
Patent No.
5,704,520. 'The electrolytic cell contains electrodes and electrolyte.
Suitable electrolytes are disclosed to be sodium bicarbonate and potassium acetate.
While these prior art references describe useful electrolytic cells, there remains a need in the an for improved el~trolytic cells useful in drug delivery devices.

~ p~cular, there is a need for electrolytic cells having a more constant rate of gas production and electrolytic cells having a controlled variable raie of gas production. The present invention satisfies these needs.
S~IAItY OFTHE ~~UN
s The present invention is directed to an improved electrolytic cell having a new electrolyte andlor a new electrode composition for water electrolysis or other type of electrochemical reaction. The invention also encompasses pre-treatment protocols for electrodes which produce a more efficient electrolytic cell. 'The electrolytic cell is useful to as a gas genemmr in a drug delivery dcvicc.
The improved cell allows for miniaturization of the electrolytic cell and any device incorporating such a cell. The novel electrolytic cell is one of the smallest electrolytic cells comprising a liquid electrolyte. The mixuaturization or micronizatiotl is possible because the cell delivers a large amount of gas volume as compared to the size 15 and quantity of components. The miniaturized electrolytic cell can be used in human applications, such as far ~dmirlistering drugs to be applied either externally or internally.
Tn addition tn being useful on a small scale, the electrolytic cell of the invention can be scaled-up and used in commercial manufacturing settings.
In a fast embodiment, the improved electrolytic cell extn~bits a constant 2o race of gas production over a prolonged period of time- For this type of cell, the anode roust be insoluble in an anodic dissolution process, which is an ele~cochemical reaction (this is distinguishable from chemical or other types of dissolution); the cathode can be chosen from a wide variety of materials. Steady state production over an extended Period of time, as shown below, is highly desirable as such a constant raze produces a constant 25 rate of drug delivery when the electrolytic cell is employed in a drug delivery device.
R.~r of Gas Tane In a second embodiment, the electrolytic cell can be designed to have a controlled variable rate o f gas production, as shown below. For this type of cell, the anode is soluble, such as brass or copper. Such a variable rate is desirable for certain types of applications, such as delivering pain medication, in which it is preferred that an initial high delivery rate is followed by a lower constant rate.
Rate of gas prcr~uctiun Time Ia a third embodiment, the electrolytic cell is designed to have an pulsati.Ie rate of gas production, as shown below. For this type of ceh, the anode is insoluble material in an anodic dissolution ptncess, which is an electrochemical reactiop (this is to distinguishable from chemical or other types of dissolution); the cathode can he chosen from a wide variety of materials. Such an izzternuttent rate of gas production is useful for certain types of applications, such as for irrigation systems, for the ~.ddition of fertility materials to irrigation water, and for administering insulin or hormones tp mammals.
Rate of gas producunu Time An electrolytic cell of the invention is dramatically superior to prior art cells in that it is simple and gist effective to manufacture, it is composed of materials that are safe and non-toxic, and it can b$ used in a variety of applic$tions. For example, au electrolytic cell according to the invention can be used in a drug delivery device to ~mixlzster a steady and controhed amount of drug over an extended period of tune.
Alternatively, the an electrolytic cell according to the invention can be used to administer a high amount of medication it~ediately following use, followed by a lower steady rate of admiilistracion, or the electrolytic cell can be used to administer a drug at intermittent periods of time.
l0 A. New Electrolyte The new electrolyte and/or electrode composition are useful in an electrolytic cell comprising the electrolyte and at least two electrodes (anode and cathode) connected to an external source of electrical current, such as a battery, for generating gas.
1u use, the electrolyte conducts electrical current between the electrodes and, as a result of an electrochemical reacrion, gas is generated. The rate of gas production corresponds to the electrical current supplied to the electrolyCic cell, and the total asxtount of gas produced is related to the electrical ceutent supplied to the cell during the time of operation.
The new electrolyte is di potassium hydrogen phosphate solution, KzHP04.
Less alkaline Phosphate buffer (i.e., KzHPO~ + KHzP04) may also be used as an electrolyte. The preferred pH of the electrolyte is about 8.0 to about 11.0, and the preferred concentration of the electrolyte is from about 1 to about 6 M. For example, the pli of 5.50 - S.SS M K~HP~, solution is 14.5 to 11Ø The pH of the solution can be reduced so any desired value, such as reducing the pH frotu I1.0 to 8.0, by adding a proper amount of phosphoric acid of the same molariry. Such a method does not change the concentration of the electrolyte solution.
With the use of a low level of curre'rlt, i.e., less than about 2 tllA, the electrolyte is preferably present at a concentration of about S.SO to 5.55 M.
With the use of a high level of current, r. e., greaser than 7 tnA, the cottcentratian of the electrolyte is S

preferably from about 1 M to about 2 M. The new electrolyte is inexpensive, non-toxic, safe, attd simple to produce.
An electrochemical gas generator having the new electrolyte delivers gas for an extended period of time. The presence of reactants in suitable atuounts and the volume of electrolyte solution are two of the factors which determine the life of the electrolytic cell. Thus, large scale electrolytic cells eau operate for years as long as a su~cient guantiry of electrolyte solution is present in the cell. The practical limitation of the life span of a uiicrouized or miniaturized cell is the time it takes the electrolyte solutiotl to dry. This is because the electrcxhemical reaction consumes a relatively to negligible amount of water compared with the volume of gas produced. Thus, if water is added to the cell it can be re-used almost indefinitely.
The new electrolyte can be used in any water-electrolysis based electrolytic cell operating at Iow currents, as well as other types of electrolytic cells operating at high or low currents. The ceps can be used, for example, in drug delivery devices, such as those described ip U.S. Patent Nos. 5,242,406; 5,062,834;
5,704,520;
5,090,963; aad 5,186,805, which are specifically incorporated by reference.
A drug delivery device incorporating the new electrolyte can be used, for example, in low-cost disposable devices for one-time use and in devices that may be fixed to a band or strap for attachment to the body, e.g., the arm, of the persop to receive the 2o medicament dispensed from the device.
B. Electrode Comp4sitiou Yet another aspect of the invention is directed to the use of various materials for the elecirade. Modification of electrode materials can result in a modification of the rate of gas production, which can thereby control the rate of a substance being delivered. Preferred anode eomposirions for producing a steady rate or pulsatile rate of gas production are certain noble metals, stainless steel, and nickel.
Useful noble metals are, for example, platinum, iridium, rhodium, ruthenium, osmium, and alloys thereof. Gold, or alloys thereof, can also be used, although gold is not preferred because it can cause high overvoltage. Alloys of noble metals for use in anodes of electrolytic cells having steady rate or pulsatile rate of gas production do not contain metals which are soluble in an electrochemical reaction. Stainless steel is preferred as it is inexpensive. Prefezred anode compositions far producing an initial high rate of gas production, followed by a lower steady rate of gas production, are brass and copper_ Cathode compositions for all three types of gas rate production (steady state, pulsatile, and controlled variable) can be selected from a wide range of materials.
The anode and cathode for alI three types of applications can be made of the same or different materials- ff the shelf life of the electrolytic cell is to be short, then diffetent materials can be used for the anode and cathode compositions.
However, if the to shelf life of the electrolytic cell is to be Iong, then it is preferred that the anode and cathode are made of the same material to avoid potential corrosion during storage.
A device having att electrolytic cell and controlled changes in gas evolution can be used, for example, for pain treatment. Such a device could be used for the delivery of morphine. At initiation, a patient requiring pain treatment requires a high rate of drug delivery. After the initial treatment period, however, the rate of drug delivery must decay. With the use of an electrolytic ptunp having controlled changes in gas evolution, a drug delivery device cap provide a high rate of initial delivery followed by a ~e~y lower raze of delivery. Such a drug delivery device is dramatically superior to prior art delivery devices, as it does not rewire smart electronics or any other complicated mechanism, and thetefot'e, is simple, efl~cient, and cost-effective.
C. Treatment Prptocol far ~lecti'c>de Surface One of the critical parameters of an electrochemical reaction is the initial condition of the electrode surface area. If the electrode surface area is clean and free of axt organic or other film or adsorbed species, it is active and electrochemical reactions using the electrode will have high current e~tciency.
There are many different methods of pre-treating electrode surfaces, such as mechanical, thermal, chemical, and electrochemical treatments. The method chosen depends upon the intended use of the cell, the electrode design, the nature of the 3o electrolyte, and the cell desi~. One popular chemical pretreatment method for platinum electrodes uses a 'piranha" solution, consisting of a mixture of sulfuric acid and hydrogen peroxide.
For use of the electrolytic cell of the invention in a mil~iaturized form at low currents, the initial electrode surface is significant as the efficiency of gas delivery is critical. If the electrode Surface in such a device was not pretreated, the gas evolution of the device may be unstable (t. e., a non-linear drug delivery curve), the drug delivery may be initially delayed because the current would have to penetrate the electrode surface fiirtt, and the repeaiabiliry of the results would be poor because the initial electrode surface wpuld rtpt be controlled- '1~ is most significant for drug devices, as regulatory approval to of such devices requires that results are repeatable and consistent.
The pretreatment process of the invention campuses pretreating stainless steel, copper, or brass electrodes by washing ~~ e~Yl alcohol and rinsing, dipping the electrodes in citric acid and zin~g~ followed by activating the electrodes with the electrolyte. A pretreatment process for nickel electrodes is also disclosed_ Both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as claimed. Other objects, advantages and novel features will be readily apparent to those skilled in the art from the following detailed description of the invt~tion.
~3LtIEF DIiSCRIf'fIDN U~ THE FIGURES
Figure 1: Shows a graphical comparison of gas delivery over time for tlu'ee different electrolytic cells having stainless steel elecwodes and 5.5 M KzHpO,as an electrolyte;
Figure 2: Shows a graphical comparison of Faradaic current efficiency over tune for three different electrolytic cells having stainless steel electrodes and 5.5 M
KzHPO~ as an electrolyte;
Figure 3: Shows a graphical comparison of cell potential over time for three different electrolytic cells having brass electrodes and an eleWrolyte composition of-. (1) 5.5 M KzHPO,; (2) 5.5 M K,~HPUq and EhTA; and (3) S.S M. KZHPO4 and sulfamic acid;
Figure 4: Shows a graphical comparison of cell current over time far ttuee different electrolytic cells hawing brass electrodes and electrolyse compositions of (1) S.S M. I~HPO,; (2) S.S M. K~iPO, and EDTA; and (3) S.S M. K2HPQ4 and sulfaxnic acid;
Figure S: Shows a graphical comparison of gas delivery over time by three different electrolytic cells having brass electrodes and electrolyte compositions o~
(1) S.S M. K~PO,; (2) S.S M. K~P~, and EATA; and (3) S.S M. K~I~PO, to and sttlfamic acid;
Figure 6: Shows a graphical comparison of a normalized reaction rate for gas for three different elecixolyte cells having brass electrodes and electrolyte compositions of (1) S.S M. K~iP~4; (2) S.S M. KzHP04 and 13DTA; and (3) S.S M. KzHPa4 and sulfamic acid;
is Figure 7: Shows a graphical comparison of gas delivery over time for three different electrolytic cells having copper electrodes and electrolyte compositions of'.
(1) S.S M K~F'~4and 40 mM F~TA; (2) S.S M ICzI~O,and 20 mM
EDTA; and (3) S.5 M KzHP4, and 10 mM EhTA;
Figure 8: Shows a graphical comparison of the normalized reaction rate for gas over 2o time for tluee different electrolytic cells having copper electrodes and electrolyte compositions of: (1) S.S M K~PO, and ~40 mM EDTA; (2) S.S
M K~iP~, and 20 mM FhTA; and (3) S.5 M K~iPU, and 10 mM EDTA;
Figure 9: Shows a graphical comparison of the normalized reaction rate for gas over tune for two different electrolytic cells having copper electrodes and 25 electrolyte compositions o1: (1) S.S M Kzl;iP4,and S0 mM sulfamic acid;
and (2) S.S M KzHPO, and 20 tnM sulfamic acid;
Figure 10: Shows pulsatile gas delivery for an electrolytic cell having 1 M
K~iPO, as an electr4lyte; and Figure 11: Shows pulsatile gas delivery for an electrolytic cell having 3 M
KzHl?O, as 30 an electrolyte.

ETAILE DESC O OF THE INVENTION
The present invention is directed to an improved elecuolytic cell having a new electrolyte andlor a new electrode composition for water electrolysis or other type of electrochemical reaction, and a pre-treatment protocol for electrodes which produces a more e~cient electrolytic cell.
'The electrolytic cell delivers gas aI a stable rate and a relatively high Faradaic current ef~cierlcy of, for example, about 70 to about 95%. For electrolytic cells to having a steady rate. P~s~~le rote, and controlled variable rate of gas production, gas is produced at a rate of from about 0.401 rng/hr up to about 24 ml/hr.
The electrolytic cell of the invention comprises at least two elecpndes and the electrolyte of the invention. The two electrodes can be made of the same or different materials, and the electrodes can be made of coated or composite materials.
The cathode IS can be made of a wide variety of uietal~. The problematic electrode is the anode due to potential corrosion with certain types of metals.
A, The New Electrolyte Di potassium hydrogen phosphate, T~,sHP4" or less alkaline phosphate ?0 buffer electrolyte, is completely safe. Futthernwre. u? contrast to many prior art , electrolytes, the navel electrolyte of the invention does not contain chloride ions. This is significant as an electrolyte containing chloride ions promotes corrosion of the anode if the electrodes are not made of a noble metal.
The pew electrolyte is superior to prior art electrolytes as it has a 25 significant buffer capacity that prevents electrode corrosion. Corrosion is one possible side reaction if the anode used in the electrolytic cell is not made from a noble metal. To ensure the stability of gas evolution and high current efficiency, ii is desirable to avoid side reactions (except when the electrolytic cell is designed to deliver a controlled variable rate of gas production).
34 poring water electrolysis, there are natural pH changes in electrolyte near the electrodes. The pH near the anode decreases because the electrolyte near the electrode IO

consumes OH ions due to the electrochemical reaction of oxygen evolution. As a result, anode media becomes more acidic, thereby causing anode corrosion. However, an electrolyte can prevent such pH changes if it has a buffer capacity pli re~~g constant near the electrodes- This was demonstrated in I1.S. Patent Nos. 5,186,805 and 5,090,963, in which the only electrolyte tested having a buffer capacity, sodium bicarbonate, showed the best results. However, the novel electrolyte is superior to the prior art NaHC03 electrolyte in that the buffer capacity of T~zHPC., is significantly greater than that of NaHC03.
While soditun bicarbonate has a buffer capacity, there are other properties 1Q of the novel electrolyte which are not matched by this prior art electrolyte. The new electrolyte of the invention also Prevents corrosion due a build up of a protecting film of phosphates on the electrodes. Specifically, high concentrations of phosphate ions cause polyphDSphate creation in the electrolyte solution and on the electrode surface. See Cotton et al., Advanced ~rcorganic Chemistry; A Comprehensive ?'ext, Part 2, page 370 (Interscience Publishers,1969). This is significant as the phosphate ions protect the surface of both electrodes from contamination and prevent anode corrosion.
This superior property of the novel electrolyte of the inveritiou is not found with prior art electrolytes, ag it is a characteristic typically only found with phosphates.
Prior art references, such as I1.S. Patent N°. 5,186,805, also teach the use of acid electrolytes, which are problematic for water electrolysis. This is because acidic solutions cause corrosion of the anode and high overvoltage of oxygen evolution. High ovetvoltage of the oxygen evolution electrochemical reaction results in increased cell potential and loss of electrical energy. Thus, alkaline solutions are preferred far water electrolysis.
Yet another benefit of the new electrolyte when it is used at a high concentrarion, i.e., above about 5.5 M, is that the electrolyte has a high hya'oscopicity, which prevents the electrolyte solution froth drying during use of the cell, thereby allowing miniaturization of the cell. In contrast, sodium bicarbonate, a comm4n prior art electrolyte, is not hygrosGOpic and would likely dry with any exposure to the 3o environment. In addition, the amount of dissolved oxygen in the electrolyte is negligible as shown by electrochemical measurements. 'this is significant as dissolved oxygen can promote anode corrosion. At high concentrations, l~~iPD~ functions to minimize the dissolution of oxygen in the electrolyse.
Moreover, the novel electrolyte is very conductive, with measurements showing conductivity of 112.5 mS/cm at 5.5 M, and 176.5 tnS/crtt at 2 M.
Nat all alkaline solutions produce superior electrolytes for use in a water electrolysis el~trolYac ceh- A 6 M solution of potassium acetate was tested in au electrolytic cell. This compound is hygroscopic, concentrated, and alkaline-However, potassiutu acetate is not a bu~'ea. Thus, it was not surprising that with the use of 1p potassium acetate as an electrolyte, th$ stainless steel anode of the electrolytic cell showed significant corrosion, which increased with electrolysis. As noted above, buffer capacitance is a benefit of the new electrolyte.
8. Limitations an the pesign of Electrolytic Cells of the lnventiou 1. Quantity of Electrolyte The natural litnstation of the reaction time of an electrolytic cell of the invention is the quantity of elecitolyte. An electrochexnica.l reaction cau be represented schematically by the following equation:
rnA-rnl3->pC+qD
2Q A and B are reactants attd C and D are products; m, ~ P~ ~d q are stoichiomettic coefficients. Consuming the reactants over time leads to an increase in diffusion overvoltage, decrease of reaction tale, possibly pH changes, and in the case of a soluble anode, possible c4niatnination of the electrolyte with sludge. Therefore, itnnay be necessary to add compounds to commercial electrolytic baths to correct the pH, f lter 2S electrolyte, etc. This shows the electrolyric cell to operate for an additional period of time. Replacing the anodes ox all of the electrolyte is usually only required after months or years of operation for industrial-site electrolytic cells.
There are two possible time limitations for the length of operation of micronized cells due to the la~cl: of water: electrochemical decomposition of water and drying of the electrolyte. Fnr water electrolysis, the electrochemical decomposition of water is schematically written as follows:
2 HZCa -~ 2 I~T + 02 The amount of water consumed in this reaction is relarively small compared with the volume of gas produced. Theoretically, 36 microliters of water are converted to 73 rnililitei's of gas at 25°C. Thus, this reaction allows the cell to operate for extended periods of time and it is unlikely to be a limitation upon the operating time period for a cell.
In cotninercial baths of water electrolysis, water generally has to be added to because of evaporation and not because of electrochemical decomposition of water. In a micronized cell having about 0.2 ml or less of electrolyte, drying can be critical to operation of the cell. The cell caa't be completely enclosed to avoid drying because a gas outlet must be present. This problem was solved by using highly hygroscopic electrolyte solution, which minimizes the rate of drying of the cell. Operating time of such a cell, 15 without the addition of water, is from about a week to a ruonth. After this tirtte period, the electrochemical reaction become ine~cient, although the cell may continue to operate.
Additional limitations on the time of operation of a cell are possible contamination of the electrolyte from the environment and possible contamination wish corrosion products or sludge, which can result when soluble anodes are used in the 2o electrochemical cell- For example, brass and copper can be used in art electrochemical cell initially delivering a high rate of gas, followed by a lower steady rate of gas. The steady slate delivery period is limited by the existence of the soluble anpde material. This time limitation will likely occur after drying of the electrolyte (the most crirical time limitation factor far operation of the electrochemical cells of the invention). For example, 25 assuming that I00 ~A is the current fraction responsible for copper anodic dissolution, the amount of copper dissolving per hour is 0.12 mg (Faraday's law). Also assuming that the volume of electrode immersed into solution is about 1.3 g (typical for a miniaturized cell), the ume limit because of arrodic dissolution is l0,Sd0 hours, which is more than one year.

2. Electrode Surface Area The primary ]imitation of minimising the electrode surface area and, as a result, th.e size of an electrolytic cell, is the current density, which is the current divided by the electrode surface area. The current density should be kept constant for the same reaction conducted in different types of cells. Thus, the required current density can.
restrict the minimal electrode surface area required for an electrolytic cell.
For example, assunziug that a water electrolysis cell of the invention operates with a 1.5 mA current and a elecuode surface area of 0.23 cm=. This correlates with a current density of t .5/0.23 = 6.5 tnA/cm2. This current produces about I tnl/hr of g~ (fuming the current e~ciency is < 100%).
Current density is significant because reaction overvohage in electrochemistry is dependent upon it. Cell ove~oltage is the difference between the cell voltage (with a current flowing) and the opcu-circuit voltage (ocv) (which is the cell voltage under zero current conditions). The cell overvoltage is the sum of overvoltages of 15 both electrodes plus the IR drop. The overvoltage represents the extra energy needed (an edgy loss) to force a slow reaction to proceed at a required rate. Thus, a high overvoltage is undesirable, as ii represents a higb energy loss.
High xeaction nvervoltage results in an unstable electrolytic cell, a loss of electrical enetgy, shorter time of battery discharge, and a decrease of the cuaent_ 20 Furthenuare, high reaction overvoltage card result in a cell which is uwre susceptible to contamination of the electrolyte.
When the current density increases, the avervoltage increases. Thus, in designing an electrolytic cell it is desirable to keep the current density relatively low to avoid high ovetvoltage. This can be done by choosing a electrodes having a sufficient 2$ surface area in relationship to the intended voltage to result in a low current density. A
lower intended current allows for the use of electrodes having a lower surface area, and conversely, a higher current requires the ttse of electrodes having a greater surface area, to obtain a desired low current density.

C. irlectrode Campositian The anode apd cathode for steady state, pulsatile, or a controlled variable rate of gas production can be made of the same or different materials. It!
general, metals that chanicallY react with water, such as alkali or a~~e'~ met' ~°uld not be used for electrode materials. In addition, metals having a low standard electrochemical potential, such as zinc, aluminum, tin, etc., should not be used as electrode materials as they will corrode with exposure to the electrolyte. Highly toxic materials, such as lead of cadmium, should not he used as anode materials, although they can be used as cathode materials. Metals or literal alloys, electrodes with modifications made to the surface, or lo carbon electrodes, 4pg ~ ~h electrode at lower ovetvoltages are preferred.
For a steady rate or pulsatile rate of gas production, the anode is insoluble, ~ can be certain noble metals, stainless steel, or pare nickel. Useful noble metals are, for example, gold, platinum, izidium, rhodium, ruthenium, osmium, and alloys thereof.
Stainless steel is preferred as it is inexpensive. For steady state or pulsatile delivery, t5 metals capable of dissolving anodically, such as brass, zinc, copper, cobalt, bright nickel, lower grades of steels, silver, etc., should be avoided as anode materials because an insoluble anode is required for water electrolysis. For a controlled variable rate of gas production, the anode is soluble, such as brass or copper.
While the cathode for steady state, pulsatile, and controlled variable rate of 2o gas delivery may be selected froth a wide range of materials, certain materials should not be used. Metals capable of absorbing hydrogen, such as palladium and niobium, or reducing to hydrides, such as titanium, zirconium, and tantrum sl~uld not be used as cathodes as they will critically decrease the current efficiency of the cell operation.
Tungsten, molybdenum, and titattitttn should not be used as cathode materials because 25 oxides of these materials can absorb hydrogen, which can decrease the current efficiency of the cell_ Provided below is a chart showing poteptial anode and cathode materials for water electrolysis electrolytic cells (steady state or pulsatile rate of gas delivery)- For a cell having a controlled variable rate of gas delivery, the anode is made of brass or copper (soluble anodes) as descnhed above, and the cathode can be made of the cathode materials given in the following table.
_TALE 1 Potential Electrode Materials far Electrolytic Cells Haying a Steady State or PuLsatile Rate of Gas Delivery (Water Electrolysis, Electrolyte is K2HP(aq at 1b M ) bode Material Commepts xbaut Cathode MaterialComments about Number Anpde Cathode 1 Stainless steel Stainless sicel 2 Nickel (>99 Nickel No limitaROn ~o) far Ni kind or its alloys 3 Platinum Platinum ~cludinghow overvoltagC
_ platinum black q Indium Iridium S Rhodium LaW overvoltaSeRhodium 4 gnnun High oxidation,Ruthcnium Its oxides rcduce overvolmgc for oxygcn evolution. A
very good 2nodc 7 O Osmium ld High avervolta~e G

g Gold High ovarvohageo 9 Titanitun oxidation StwGr I 1 Cobalt 1Z CoPIKT

13 Alloys of uientionad Alloys of mentioned )s 14 Modified elcctrc~des- Modified electrodes.

Examples: Fxa~le: platinum (1) tutheouun powder on Carhop dipxide on nickel surfacc (2) Conductive oxidrs as epode to In general, the epode and cathode for all three types ef applications (steady state, pulsati)e, and controlled variable rate of gas production) can be made of the same pr different materials. If the shelf life of tho electrolytic cell is in be short, then different materials can be used for the anode and Cathode compositions_ However, if the shelf life of the electrolytic cell is to be long, then it is preferred that the anode and cathode are made of the same material to avoid potential corrosion during storage. If both the anode and cathode are made of a noble metal or noble metal alloy (gold and all metals from the p~t~~ ~~p), then the anode and cathode can be made of different materials, reg~dless of the intended shelf life of the ceh. This is because these materials will not corrode during storage.
If the electrodes are made from noble metals (cases 3-8 in the Table), then there are more possibilities for the choice of electrolyte- Noble metals do not dissolve auodically, so the requirements for the electrolyte may be reduced: i.e., it is not required that the electrolyte he a bufFer and the electrolyte may have a neutral, acidic, or alkaline p#1. The electrolyte in the cell must be hygros~pic and safe and it must contain 1o compounds suitable for evolution of safe gases duripg electrochemical performance.
Several examples of such compounds are:
(1) Aluminum salts- sulfates ornitrat$, orpota~siuut alum: KAl(SO~_ These salts are very hygroscopic and potassium alum is extremely inexpensive.
The pH is slightly acidic. The electrochemical reaction is electrolysis of 15 water.
(2) Hydrosulfates of alkaline metals (KHS04 or NaHS04). The pH is acidic and the electrochemical reaction is electrolysis of water; and (3) Acetates, formates, or propionates of alkaline metals. The pH is alkaline.
The electrochemical reactions are: (a) electrolysis of water, and (b) gas 2o COi evolution. This means that: (t) on the anode there is oxygen evolution and CO~ evolution (Kolbe reaction) (E_ Gileadi, Electrode Kinetics, Part 1, p. 209 (VCH publishers,1993)) and (ii) on the cathode there is hydrogen evolution. All of the gases are safe.
p. Use of the New Elertrptyte in Different Types of ~IectrpIytac Celts 1. Use of the New Electrolyte in Cells Having Different Levels of Current The new electrolyte can be used in electrolytic cells having varying levels of current. For example, the K~iP04 electrolyte can be used in an electrolytic ceh having a high level of current, i.e., above about 7 ruilli.Ampers. With this type of ceh, a relatively low concentration of electrolyte should be used, i.e., less than about 2 M.
In a first test, an electrolyte solution of about 5.50 M to about 5.55 M
solution of KzI3P~, was used in the high current cell. A high current results in a high rate of gas production. Use of such a high concentration electrolyte in a high current electrolytic cell required an enlarged elecpro~e surface su~cient for performance at high cturent. I-lowever, it was discovered that such a high concentration electrolyte produced a slow cpalescence of creating gas bubbles, forming a solution that resembled an emulsion.
~e high viscosity of the electrolyte solution prevented the transfer of gas bubbles out of the cell, and resulted in a significant increase in the cell potential at a constant current, without reaching a plateau. This means a high diffusion overvoltage on bath electrodes and an increase of the resistance of the solution., producing a high IR drop.
An IR drop is a loss of potential caused by current and resistance of the solution. As the IR grows, the loss of energy in~'eases- Thus, liven the Level of the cuxrent for this electrolytic cell, the IS resulting gas delivery was too slow.
A relatively low concentration K~HPO, electrolyte, i.e., an about 1 M to about 2 M solution of K.~~P04, is preferably used in an electrolytic cell having a high level of current. For example, a 2 M solution of ICzHP04 used in an electrolytic cell operating at a high cuxrent Ia~ed any coalescence problems. Thus, a lower concentration of the electrolyte allows operation of an electrolytic cell at a higher current.
At Low concentrations, the ~, elec~lyte is extremely conductive, with a Conductivity of 176.5 mS/cm at 2 M. This is important when operating an electrolytic cell at a high current, as this is when IR drop becomes significant. Moreover, the lower concentration ICzHf04 electrolyte is even more conductive than the high concentration K~HP~, electrolyte: at 2S°C and a 2 M solution, the conductivity is 176.5 tn.S/cm, while at the same temperature a 5.5 M solution is 112.5 mSlcm. The difference in Goxtdurtiviry is Likely caused by a more complete dissociation pf ions for the lower concentration IC2HP04 electrolyte. The lower concea~non K~if O, electrolyte is also hygroscopic, although its hygroscopicity is lower than the more concentrated form of the 3o K~HPO, electrolyte.

WO 01/79706 PCT/EPOi/04265 2. use of the New Electrolyte in Cells Having a Controlled Variable Gas Delivery Rate Over a Period of Time The present invention also encompasses electrolytic cells which deliver gas at a controlled variable rate over a period of time. In such a cell, the rate of gas generation starts off high followed by a lower steady rate of gas g~eration.
The rate of gas generation of this type of electrolytic cell is shown in Figs_ 6 and 9.
The rate of gas delivery depends upon: (1) the current flowing through the cell, and (2) the current e~ciency of the particular gas evolution reaction, i_e., the IO presence tar absence of side rcactiot~. Thus, tbG rate °f 8~
delivery can be c4ntrolled by choosing a combination of el~trochemical reactions. The reactions can be chosen by changing the electrolyte, the electzode material, or both ~ well as the resistor. A pump having controlled changes in drug delivery can be obtained by designing such an electrolytic cell.
For example, with the use of brass electrodes, zinc and copper provide anodic dissolution producing anode salt passivation, which occurs when the anode surface is coated and blocked by a salt fllIR. This phenomenon, which occurs because of the low solubility of the zinc and copper phosphates, produces a sudden intensive increase in the cell potential and a corresponding decrease in current. Thus, following an initial high rate of gas production, the rate of gas delivery breaks and decreases, staying constant thereafter.
Following the occurrence of anode salt passivation, the cell potential will be high enough for water electrolysis, i.e_, about 2V. Water electrolysis starts but has a very low current efficiency because of significant side reactions on both electrodes: on the anode, zinc and copper are dissolving and oxygen is evolving, while en the cathode, copper is being deposited and hydrogen is evolving. This is in contrast to the initial period of operation of the cell, in which zinc and copper anodie dissolution occurs, while only a high rate of hydrogen evolution occurs at the cathode.
The length of the initial time period of a high rate of gas producrion prior to anode salt passivation depends upon the level of current used in the cell.
Higher current produces a faster rate of phosphate production in the electrolyte, resulting in a faster onset of salt passivation and a consequent increase of cell potential.
The theoretical limit of maximum time of cell operation is very prolonged g 3. Use of the New Electrolyte in Cells Havlng Pulsatile Current The present inventipn also encompasses electrolytic cells which deliver gas at a pulsatxle rate over a period of time. In such a cell, the rate of gas generation starts and stops as the current starts and stops. 'The rate of gas generation of this type of electrolytic cell is shown in Figs. 10 and I I _ The best perfortnance Af hormones, such as human gmwth hormone or fertility hormones, is obtained with pulsatile delivery rather than continuous delivery.
(This is a chat'acteristic of hortuones.) A pulsalile insulin delivery device utilizing the electrolytic cell of the invention can be designed to delivery insulin at a specified time schedule, i.e., raze level I during the da.Y ~ ~e level II at night. The pulsatile delivery is obtained by starting and stopping the correttl run through the device. The tune of starting and stopping can be triggered by a timing device incorporated into the delivery device.
E. Use of the New IElectr4tyEe and/4r Electrode Coutpasitions 2o in au Electrolytic Cell in a Drug Delivery Device The new electrolyte audlor the new electrodes can be used in electrolytic ceps which funcrion as gas generators for continuous or pulsatile ditag delivery devices.
For example, an electrolytic cell according to the invention can be used in a low-cost 2s disposable device for single use. Such devices can be fixed to a band or strap for attachment to the body, e.g., the arm, of the person to receive the medicament dispensed tram the device.
Such a device comprises a power supply for energizing the electrodes. The power supply preferably includes a battery and an electrical control circuit for controlling 3o the rate of energization of the electrode, and thereby the rate of dispensing the liquid from the container. Such an electrical colitml circuit preferably includes presectable means for presetting the rate of energization of the electrodes, and an electrical switch foT
controlling the energization of the electrodes.
A miniaturized cell for use in the human body preferably has a minimum of'/z to 1 ml of electrolyte solution. Commercial size electrolyte cells can have 100's of liters of electrolyte solution. A typic&1 miniaturized electrolytic cell for use in an external drug delivery device has a minimum of about 0.15 rnl of electrolyte solution.
The use of about 0_15 ml of electrolyte solution in a cell utilizing conventional electrodes resulted in a cell having a high potential. Therefore, electrolytic cells having quantifies of electrolyte less than about 0.2 ml preferably employ special electrodes having a larger surface area Io than conventional electrodes. A miniaturized electrolytic cell having about 0.2 mI of electrolyte solution can produce gas for a period of over 200 hours, i.e_, for a week or longer.
F'. Electr4de Pretrearrnent Nlethpd The electrode pretreatment method of the invention is useful for electrodes to be used in electrolytic cells. The pretreatment produces cells having consistent and repeatable results. The electrodes can be made oiy far example, stainless steel, copper, brass, or nickel.
For staialegs steel electrodes: fhe electrodes are first washed in a 2o solution of absolute or 95% ethyl alcohol. Preferably, the electrodes are washed in an ultrasonic bath in a closed glass vial for about 30 to about 40 minutes. This step removes fats and prgamc materials (dirt) from the electrode surface. The electrodes are then rinsed in deionued or RO (reverse osmosis) water.
This is fahAwed by dipping the electrodes in a solution of about 5% citric acid iti deianized ar RO water- Preferably, the electrodes are dipped at 40-454C for about to about 40 train. 'This step removes oxides or other remaining film from the electrodes. The electrodes are then rinsed in deionized or RO (reverse Osmosis) water.
Finally, the electrodes are stored in the electrolyte solution (K2HP0~ for less than about 10 minutes to up to several days. The purpose of this step is to keep the electrode surface active and to prevent oxidation and contamination of the surface from exposure to the air.
For copper and brass electrpdes: The process used for stainless steel electrodes is slightly modified for copper and brass electrodes. For copper electrodes, , the dipping step was performed without the addltaon of heat and far a period of about 15 to about 20 minutes. For brass electrodes, the dipping step was performed without the addition of heat and for a period of about 5 to about 10 minutes.
Far nickel electrodes: The washing and storage steps for nickel electrodes are the same as for stainless steel electrodes. The two processes differ in the l0 dipping press. Pure nickel exposed to air has an oxide film on its sutface (as does stainless steel). However, the nickel film is much more stable than that present an stainless steel.
Three alternative dipping solutions were developed for the nickel electrodes. The fast solution comprises citric acid, ammonium acetate, and FDTA at an is acidic pH. Preferably, the citric acid is present at about O.s M, the ammonium acetate is present at about 0.2 M, and the EDTA is added until dissolution.
The second dipping solution comprises citric acid, ethylenediaanizte, and a reducing agent, such as NaHSO,. Fteferably, the citric acrd is present at a concentration of about 1 to about 2 M, the ethylenedie is added until the pH x'em~ ~l~c (pH
of 2o about 5), and the reducing agent is present at a concentration of about 0.01 M, depending upon the agent used.
The third dipping solution coulprises ammonium nitrate, citric acid, triethataolamine, and a reducing agent, such as NaHSO, or sodium formaldehyde bisulfate.
Preferably, the ammonium nitrate is present at a concentration of about 2.5 M, the citric 25 acid is present at a copcentration of about 0.01 M, the triethanolamiue is present at a concentration of about 0.05 M, and the reducing agent is Present at a concentration of about 0.01 M, depending upon the agent used.

The following examples are given to illustrate the present invention. It should be understood, however, that the invention is not to be limited to the specific conditions or details described in these examples. Throughout the specification, any and all references to a publicly available document, including U.S. patents, are specifically incorporated into this patent application by reference.
Ezam a 1 The purpose of this example was to demonst~te the rate of gas production of an electrolytic cell having a spluttori of KzHP~, as art electrolyte.
1p Stainless steel electrodes (316 L) were used with a S.5 M solution of p4 as an electrolyte in three electrolytic cells. The electrodes had a diameter of 0.8 ntrn, a length immersed in solution of 9 mm, for a total surface area of each electrode of 0.23 cm=. 316 L stainless steel was used because it is highly resiStattt to corrosion. "L"
represents low carbon concentration in the steel, which is preferable because 4f possible is electrolyte contamination with "sludge". Sludge in electrochemistry refers to particles of anode falling into electrolyte due to un-utuform anodze corTOSlOn. Low carbon content in the stainless steel yes the amount of insoluble sludge.
The pH of the electrolyte used in each cell was 10.8. No additives were used with the electrolyte. The electrolytic cells generated gas at constant rates for a 0 period of about 111 hours, with a Faradaic current efficiency of about 80 to about 100%.
The resistance of the circuit was 10.2 kOhm. The constant race of gas generation for over 4'/s days for the three ceps is shown in Fig. 1, and the current efficiency of the Ihree cells i$ shown in Fig. 2.
The delivery rate far gas generation was measured as follows: evolving 25 hydrogen and oxygen gas entered a water reservoir, pushing water via a tube into a vial on an analytical balance measuring continuahy on a time basis. The weight corresponded to the volume of gas generated (the y axis of Figure 1).
The results of this example demonstrate the efficiency and effectiveness of X04 as an electrolyse for an electrolytic cell. Moreover, this example demonstrates 30 the successful preparatiotz of a simple, cost-effective, delivery device incorporating an~

electrolytic cell, in which the rate o f gas generation is steady and constant over an extended period of time. This is significant as the rate of gas generation governs the rate of delivery of the substance contained in the device.
xa a 2 g The propose of this example was to construct an electrolytic cell that initially delivers a high rate of gas production followed by a lower steady rate of gas production.
Brass electrodes were used with a S.S M solution of K~PO~ as au elecuolyte in three electrolytic cells, having a pH of about 10.5 to abclut 11.0: Ceh A, to Cell I3, and Cell C. EDTA (ethylenedianlinete~-acetic acid) was added to Cell B and sulfarnic acid was added to Cell C. The composition of each of the three cells is summarized in Table 2 below_ T
C4mpositions of Electrplytic Cells 1S H vin V table to of G s Prod 'on Cell Electrodes Electrplyte ' Additive A Brass 5.5 M 0, None E~ 5.S M KzHPO, 20 mM EDTA

C E~ 5.5 M I~HP04 50 mM sulfamic acid The results are summarized in ~8s. 3-5. The cell potential of the three cells was rather low, at 0.85 to 0.95 V and, therefore, current was rather high. See Figs. 3 2o and ~. The resistance used was 10.9 kOhm. Initially, the delivery rite of hydrogen gas is high, as the current is initially high. In addition, the delivery rate of hydrogen gas is initially high as at the start of the reactipn there is no side reaction on the cathode (where hydrogen gas evolves). This initial period of a high rate of gas production lasts for about 7 to about 11 hours., See e.g., Fig. 5, which shows the rate of delivery over tittle, including 25 the break poiztt, for the three cells.
As the reaction progresses, zinc and copper are gradually dissolved anodically, producing salt passivation of the anode and a sudden intensive incr~se in the cell potential along with a corresponding decrease in current. ,See e.g., Fig.
~#. Once 2~

WO 01/79706 PCT/EPOl/04265 anodic salt passivation has occurs, the ceh potential is high enough for water electrolysis, about 2V. Water electrolysis starts but has a very low current efficiency because of significant side reactions on both electrodes; on the anode, zinc and copper are dissolving and oxygen is evolving; and on the cathode, copper is being deposited in addition to hy~ogen evolving. As a result, the gas delivery curve breaks after about 7 to 1 I hours, and the gas delivery rate decreases about 2 to 2.5 times, staying constant thereafter, as shown in Fig. 3.
This example demonstrates tha successful preparation of $ delivery device incorporating an electralYtic cell ~n which the rate of gas generation, which governs the l0 raze of delivery of the substance contained in the device, is initially high followed by a Iower steady rate of gas production.
EYa a 3 The propose of this example was to construct an electrolytic cell that 15 initially delivers a high date of gas production followed by a lower steady rate of gas production.
Copper electrodes were used with a S.5 M solution of KzHfO4 as an electrolyte in five electrolytic cells, having a pH of about 10.5 to 11.0:
Cell h, Cell E, Cell F, CeII G and Cell H. EhTA was added in varying amounts to three of the cells and 2o sulfatrric acid was added to the remaining two cells, as described in Table 3_ Compositions of Electrplytic Cells ~avin~Vai~able Rate of Gas Pro action Cell ElectrodesElectrolyte Additive -Ll Copper ~.S M K2HP0~ 1 Q mM F.ATA

E CApper 5.5 M KzHPC4 20 mM EhTA

Copper 5.5 M KaHT'U4 ~0 mM EIaTA

Ct Copper S.5 M K~iPC, 50 tnM sulfatnic acid Copper S.S M K~'O, 20 mM sulfamic acid The results are su~ariZ~ m Fig' ~' w~ch shows the rate of delivery over time for the iluee ~DTA cells; acrd Figs- $ ~ 9, which sh4w the normalized reaction rate over time for the three EDTA cells and the sulfauuc acid cells, respectively.
There are two primary di~ere~~ between a cell having h~ electrodes sample 2) and a cell havuig coPFer electrodes. First, there is no break pint in the delivery curve bccause salt passivation does not occur with copper electrodes.
Second, water elecirQlysis starts immediately.
A, Lack of Savlt Passivation With Copper EleCapdeg to With the use of brass electrodes, zinc appat'endy acts as a reducing ag~t resulting in coPPer and zinc phosphate formation (with and without additives in the electrolyte). The phosphate salts are significantly ins°luble, resulting in sale passivation of the anade-In coptrast, copper electrode ceps hav~g ETA Ar sulfamic acid as 1s additives, oxygen evolution and ano~c dissolution of copper until it complexes occurs at the anode, and hydrogen evolution apd electrodeposition of copper from complexes occurs at the cathode. For a cell lacking PTA or sulfamic acid as additives, oxYg~
evolution and anodic dissolution of coPPcT until Cu0 (black powder) formation occurs at the anode, and hydrogen evolution occurs at the cathode.
,,o Cells having coPPer electrodes and ~DTA or sulfamic acid as an additive have increased anodic dissolution of copper, ~ea~g soluble copper complexes. T
his e~bles an additional catholic reaction of electrodeposition of copper frog the created complexes. The cturent fraction for both side Ieachons increases at f rst followed by reaching a steady state after a period of time.
25 'thus, the delivery rate curve for the copper electrode cells °f this example is sm~~ ~~ no break point. in addition, the main reaction raze is slightly decreasing until it reaches a constant value. The decrease of gas evolution rate can be regulated with the addition of additives.

g_ Immediate Water Electrolysis The second primary difference between cells having brass and copper elecu'odes is that with copper electrodes the cell potential is high enou~ at the beginning of cell opon to effect water electrolysis (about 2~. This is because copper anodes do S not contain zinc.
Anodic dissolution of zinc occurs at significantly lower anodic potenual than anndic dissolution of copper or oxygen evolution. The anodic dissolution of zinc, w~ch occtus with bass electrodes (followed by anodic dissolution of copper), leads to an initial cell pomual of loss 0.95 V, which is ton lpw for water electrolysis.
This example demonsti'ates the successful preparation of a delivery device incorporating an electrolytic cell in which the rate of gas generation, which governs the rate of delivery of the gibe cpntained in the device, is initially high followed by a lower steady rate of gas pr~uction.
****
1s It will be apparent to those s~lled in the art that various modifications and variations can be made in the methods and compo~tip~ of the present invention without departing from the sprit or scope of the invention. Thtts~ it is intended that the present invention cover the tnødificatiAns and variations of this invention provided they come 2A within the scope of the appended clairus apd then e4'hvalents.

Claims (39)

We claim:

1. An electrolytic cell comprising:
(a) an electrolyte solution comprising K2HPO4, or a less alkaline phosphate buffer solution, in water; and (b) at least two electrodes comprising an anode and a cathode, wherein:
(i) the anode is made of a material selected from the group consisting of stainless steel, nickel, and a noble metal; and (ii) the electrodes are connectable to a source of electrical current, wherein when the electrodes are energized by an electrical current, the current is conducted through the electrolyte resulting in a gas forming at each electrode.

2. The cell of claim 1, which provides a steady rate of gas production for up to abut 200 hours or longer.

3. The cell of claim 1, which provides a steady rate of gas production for a period of time from about 1 hour to about 200 hours or longer.

4. The cell of claim 1, wherein the gas is generated at a steady rate.

5. The cell of claim 1, wherein the current is applied at a pulsatile rate and the corresponding rate of gas delivery is at a pulsatile rate.

6. The cell of claim 1, wherein the gas is generated at a rate of about 0.001 ml of gas/hour up to about 24 ml of gas/hour.

7. The cell of claim 1, wherein the anode is composed of a noble metal material selected from the group consisting of platinum a platinum alloy, rhodium, a rhodium alloy, osmium, an osmium alloy, ruthenium, a ruthenium alloy, gold, a gold alloy, iridium, and an iridium alloy wherein such alloys do not contain metals which are soluble in anodic dissolution.

8. The cell of claim 1, which has a Faradaic current efficiency selected from the group consisting of at least 50%, at least 75%, at least 80%, at least 85%, at least 90%, and at least 95%.

9. The cell of claim 1, wherein the electrolyte is present at a concentration of at least 1 M up to about 6 M.

10. The cell of claim 1, wherein:
(a) the electrolyte is present at a concentration of about 1 to about 6 M
and in an amount of from about 0.15 ml to about 100 L;
(b) the electrodes comprise stainless steel and have a surface area of about 0.19 cm2 to about 50 cm2 or more;
(c) the current is less than or equal to about 2 mA; and (d) the gas is generated at a steady rate or at a pulsatile rate and is produced at a rate of from about 0.01 ml of gas/hr up to about 1.5 ml of gas/hour.

11. The cell of claim 1, wherein:
(a) the electrolyte is present at a concentration of about 1 to about 3 M and in an amount of from about 0.2 ml to about 100 L
(b) the electrodes comprise stainless steel and have a surface area of about 0.19 cm2 to about 50 cm2 or more;
(c) the current is about 7 mA or greater, and (d) the gas is generated at a steady rate or at a pulsatile rate and is produced at a rate of at least 4 ml of gas/hour.

12. An electrolytic cell comprising:
(a) an electrolyte solution comprising K2HPO4, or a less a phosphate buffer solution, in water; and (b) at least two electrodes comprising an anode and a cathode, wherein:
(i) the electrodes are made of a conductive material;
(ii) the anode is electrochemically soluble; and (iii) the electrodes are connectable to a source of electrical current, wherein when the electrodes are energized by an electrical current, the current is conducted through the electrolyte resulting in a gas forming at one or more of the electrodes.

13. The cell of claim 12, wherein the gas is formed at a controlled variable rate.

14. The cell of claim 12 which provides a controlled variable rate of gas production far a period of from about 1 to about 110 hours or more.

15. The cell of claim 12, which provides an initial high rate of gas production for a period of from about 4 to about 15 hours.

16. The cell of claim 12, wherein the aide is composed of a material selected from the group consisting of brass and copper.

17. The cell of claim 12, where the gas is generated at a rate of about 0.001 ml of gas/hour up to about 24 ml of gas/hour.

18. The cell of claim 12, wherein the electrolyte is present at a concentration of from about 1 to about 6 M.

19. The cell of claim 12, wherein:
(a) the electrolyte is present at a concentration of about 1 to about 6 M
and in an amount of from about 0.15 ml to about 100 L;
(b) the anode comprises copper or brass;
(c) the electrodes have a surface area of about 0.19 cm2 to about 50 cm2;
(d) the current is less than or equal to about 2 mA; and (e) the gas is generated at a rate of from about 0.001 ml of gas/hr up to about 1.5 ml of gas/hour.

20. The cell of claim 12, wherein:
(a) the electrolyte is present at a concentration of about 1 to about 3 M
and in an amount of from about 0.2 ml to about 100 L;
(b) the anode comprises copper or brass;
(c) the electrodes have a surface area of about 0.19 cm2 to about 50 cm2;
(d) the current is about 7 mA or greater; and (e) gas is generated at a rate of about 0.01 ml of gas/hr up to about 24 ml of gas/hr.

21. A device for dispensing a liquid at a predetermined rate, comprising an electrolytic cell according to claim 10.

22. A device for dispensing a liquid at a predetermined rate, comprising an electrolytic cell according to claim 11.

23. A device for dispensing a liquid at a predetermined rate, compassing an electrolytic cell according to claim 19.

24. A device for dispensing a liquid at a predetermined rate, comprising an electrolytic cell according to claim 20.

25. A device for dispensing a liquid at a predetermined rate, comprising an electrolytic cell according to claim 1.

26. The device of claim 25, further including an electrical power supply for energizing said electrodes.

27. The device of claim 26, wherein said power supply includes a battery and an electrical control circuit for controlling the current of energization of the electrode, and thereby the rate of dispensing the liquid from the container.

28. The device of Claim 27, wherein said electrical control circuit includes presettable means for presetting the rate of energization of the electrodes, and an electrical switch for controlling the energization of the electrodes.

29. The device of claim 25, wherein the electrodes are composed of a material selected from the group consisting of platinum, a platinum alloy, rhodium, a rhodium alloy, iridium, an iridium alloy, osmium, an osmium alloy, ruthenium, a ruthenium alloy, gold, and a gold alloy, wherein such alloys do not contain metals which are soluble in anodic dissolution.

30. The device of claim 25, wherein the electrolytic cell has a Faradaic current efficiency selected from the group consisting of at least 50%, at least 75%, at least 80%, at least 85%, at least 90%, and at least 95%.

31. A device for dispensing a liquid at a controlled variable rate comprising according to claim 12.

32. The device of claim 31, further including an electrical power supply for energizing said electrodes.

33. The device of claim 32, wherein said power supply includes a battery and an electrical control circuit for controlling the rate of energization of the electrode, and thereby the rate of dispensing the liquid from the container.

34. The device of claim 33, wherein said electrical control circuit includes presettable means for presetting the rate of energization of the electrodes, and an electrical switch for controlling the energization of the electrodes.

35. The device of claim 31, wherein the anode is composed of a material selected from the group consisting of brass and copper.

36. The electrolytic cell of claim 1, wherein at least the anode is stainless steel, which is pretreated in a process comprising:
(a) washing the electrodes in a solution of ethyl alcohol;
(b) rinsing the electrodes in deionized or RO water;
(c) dipping the electrodes in a solution of about 5% citric acid in deionized or RO water at an elevated temperature far about 30 to about 40 minutes;
(d) rinsing the electrodes in deionized or RO water; and (e) storing the electrodes in K2HPO4 solution.

37. The electrolytic cell of claim 1, wherein at least the anode is nickel, which is pretreated in a process comprising;
(a) washing the electrodes in a solution of ethyl alcohol;
(b) rinsing the electrodes in deionized or RO water;
(c) dipping the electrodes in a solution selected from the group consisting of (i) citric acid, ammonium acetate, and EDTA at an acidic pH; (ii) citric acid, ethylenediamine, arid a reducing agent; and (iii) ammonium nitrate, citric acid, triethanolantine, and a reducing agent;
(d) rinsing the electrodes in deionized or RO water; and (e) storing the electrodes in K2HPO4 solution.

38. The electrolytic cell of claim 12, wherein at least the anode is copper, which is pretreated in a process comprising:
(a) washing the electrodes in a solution of ethyl alcohol;
(b) rinsing the electrodes in deionized or RO water;
(c) dipping the electrodes in a solution of about 5% citric acid in deionized or RO water far about 15 to about 20 minutes;
(d) rinsing the electrodes in deionized or RO water; and (e) storing the electrodes in K2HPO4 solution.

39. The electrolytic cell of claim 12, wherein at least the anode is brass, which is pretreated in a process comprising:
(a) washing the electrodes in a solution of ethyl alcohol;
(b) rinsing the electrodes in dionized or RO water, c) dipping the electrodes in a solution of about 5% citric acid in deionized or RO water for about 5 to about 10 minutes;
(d) rinsing the electrodes in deionized or RO water, and (e) storing the electrodes in K2HPO4 solution.