Iontophoresis- An Approach for Transdermal Drug Delivery: A Review

S.T. Deshpande¹*, M.P. Wagh²

bai Thite College of Pharmacy, Shirur, Pune.

²Department of Pharmaceutics, MVP’s College of Pharmacy, Nashik.

ABSTRACT:

Iontophoretic system deliver the drugs in the form of ions into the body by the use of electric current typically upto 0.5 mA/cm2. The technique is used for several decades clinically in delivering medication to surface tissues. However, its potential is recently being rediscovered for transdermal systemic delivery of ionic drugs including peptide/protein drugs which are normally difficult to administer except by parenteral route. This review describe the advantages, disadvantage and basic principle of iontophoresis with its electrochemistry. Various factors which affect transdermal absorption have also been reviewed. In the final section we summarizes the studies conducted recently using chemical enhancers and the list of drugs investigated in iontophoretic delivery system This article is focused to review old as well recent literature on the principle, Biomedical application and to provide reader a very comprehensive over view of the state of art of this potential in the new era pharmaceutical research.

KEYWORDS: Iontophoresis, Electric current, Transdermal, Iontophoretic device, Chemical enhancer, Skin

INTRODUCTION:

Skin being the largest part of human body have been explored as a route of drug administration and so far many drug delivery techniques which utilize alternative forms of energy have been used to facilitate permeation of drugs across the skin. Amongst these, iontophoresis, which is the facilitated movement of ions across a membrane under the influence of an externally applied small electrical potential difference (0.5 mA/cm² or less), is one of the most promising novel drug delivery system, which has proved to enhance the skin penetration and the release rate of a number of drugs having poor absorption/permeation profile through the skin^1,2,3. Use of electricity to increase penetration of electrically charged molecules through different membranes of our body, a process known as iontophoresis, is known for long time. Biomedical applications of iontophoresis have been around for several decades (Chien and Banga, 1989). In contrast, the use of electroporation for transdermal or topical delivery was only suggested about5 years ago (Prausnitz et al., 1993), though electroporation as a science has about 25 years of history (Tsong, 1991)⁴ Iontophoresis is the use of an electromotive force to enhance percutaneous absorption of a drag or chemical. Iontophoresis usually employs a direct current between 0.5 and 20 mA. In 1747, Veratti described the application of an electric current to increase the penetration of drugs into surface tissues. In 1900, Leduc 4 reported the first controlled iontophoresis studies in his oddly named "ionotherapy" experiments.

He applied iontophoresis of strychnine and cyanide ions into rabbits and produced tetanic seizures and cyanide poisoning.^5,6 The process of iontophoresis for local therapy has the following characteristics: (1) a charged (ionic) drug should be used; (2) the drug should be applied at the electrode of the same charge; (3) the condition or disease under treatment must be at or near a body surface; and (4) therapy is enhanced because the drug is concentrated in the tissue of application. As a side benefit, systemic effects are eliminated during short treatments for local therapy because only a minuscule amount of drug reaches the bloodstream.⁷

Review of the literature mainly involve iontophoretic system, it’s advantages, disadvantages factors affecting iontophoresis and applications.

IONTOPHORETIC STSTEM

Principle of iontophoresis ⁸

The iontophoretic technique is based on the general principle that like charges repel each other. Thus during iontophoresis, if delivery of a positively charged drug (DC) is desired, the charged drug is dissolved in the electrolyte surrounding the electrode of similar polarity, i.e. the anode in this example as shown in fig.1 by appointing electromotive force the drug is repelled and moves across the stratum corneum towards the cathode, which is placed elsewhere on the body. Communication between the electrodes along the surface of the skin has been shown to be negligible ⁹, i.e. movement of the drug ions between the electrodes occurs through the skin and not on the surface. When the cathode is placed in the donor compartment of a Franz diffusion cell to enhance the flux of an anion, it is termed cathodal iontophoresis and for anodal iontophoresis, the situation would be reversed.

Neutral molecules have been observed to move by convective flow as a result of electro-osmotic and osmotic forces on application of electric current ¹⁰. Electromigration of ions during iontophoresis causes convective solvent motion and this solvent motion in turn ‘drags’ neutral or even charged molecules along with it. This process is termed as electro-osmosis. At pH values above 4, the skin is negatively charged ¹¹, implying that positively charged moieties like Na⁺ molecules will be more easily transported as they attempt to neutralize the charge in the skin to maintain electro neutrality ¹¹. Thus the movement of ions under physiological conditions is from the anode to the cathode. For loss of each cation (sodium ion in this case from the electrode in this process, a counter ion, i.e. an anion, Cl^- moves in the opposite direction from the cathode to the anode. It is the transport number of each ion, which describes the fraction of the total current transferred by the ion and depends on the physicochemical properties of the respective ions. Na⁺ is greater than Cl^- and also the skin facilitates movement of Na⁺ than Cl^- hence there is a net increase in the NaCl in the cathodal compartment and net decrease in NaCl on the anodal side. Due to this electrochemical gradient, osmotic flow of water is induced from the anode to the cathode. If any neutral drug molecules are present at the anode at this time they can be transported through the skin along with the water. Such water movement often results in pore shrinkage at the anode and pore swelling at the cathode ¹²

Figure No. 1: Principle of iontophoresis

Routes and mechanism of iontophoretic delivery¹³

For an monogenic compound, the process of skin permeation is likely to be complicated by the simultaneous presence of both ionized and unionized species in solution, each of these permeating through the skin at different rates¹⁴. The permeability of ionized species has been reported to be much less than that of unionized species ¹⁵. For ionic drugs especially, hair follicles and sweat ducts can act as diffusion shunts^16-18. Thus, during iontophoresis, the greatest concentration of ionized species is expected to move into some regions of the skin where either the skin is damaged, or along the sweat glands and hair follicles, as the diffusional resistance of the skin to permeation is lowest in these regions^19,20. An interesting early work by Abramson and Gorin ²¹ suggested that sweat glands are the primary channels for transport during iontophoresis. Their conclusion was based on the pore patterns of the skin that developed follow ing iontophoretic transfer of basic and acidic dyes and metallic ions. For example, thorough rubbing and washing of the skin following the iontophoretic delivery of methylene blue revealed a remarkable pattern of channels traversed by the dye. The blue dots observed on the skin were found to be the sites of the pores of the skin which are the orifices of the coils of sweat glands, suggesting that the dye enters the skin via these pores. The pore patterns persisted for several weeks in many cases. A similar interpretation of the mechanism of iontophoretic delivery has also been suggested by other studies ^22-25. Papa and Kligman ²² also demonstrated that methylene blue introduced iontophoretically into the skin is observed to enter sweat glands in a punctate pattern which outlines the sweat pores. A relatively recent report by Grimnes ²⁶, using special electrodes and methods, also concluded that the dominant pathway for the ionic flow through the human skin is through the sweat ducts. additionally, a potential dependent pore formation in the stratum corneum was also reported that could be contributed by a “flip-flop” gating mechanism ²⁷. As the electric potential is applied across the skin, the flip-flop of the polypeptide helices in the stratum corneum may occur to form a parallel arrangement in response to the application of potential. Pores are thus opened as a result of the repulsion between neighboring dipoles, and water molecules and ions will flow into the pore channels to neutralize the dipole moments. The isoelectric point of the skin is roughly between pH 3 and 4, so that its pores have positive charge when ex- posed to a medium with pH below 3 or a negative charge if the pH is higher than 4 ^28,29,30. Thus, the pH of the drug solution applied can affect the iontophoretic delivery of the drug. Put temans et al. ²³ investigated the mechanism of iontophoresis by using potentiometry and X-ray fluorescence. They studied the iontophoretic application of potassium iodide to human knees and found that the iodide is taken up only when electric current is applied. They reported that about 10% of the iodide applied is noted to penetrate the skin, while X-ray fluorescence scan of the volunteer’s thyroid gland showed that the average iodine content in the gland is increased by more than 30%. The result of this study is more or less in agreement with the earlier study using radioactive iodine ^31. The intricacies of the mechanism of iontophoresis await further studies ³².

Method of delivery³³

When applied topically, the current is applied through a moist electrode, the size depending on the skin region to be treated. The drug is administered through an electrode (active) which has the same charge as the drug. This is very important; if the polarity of the electrode is not the same as the ions, then penetration through the skin may not occur. The oppositely charged electrode (return) is placed some distance away at a neutral site, the size and distance of the two electrodes would also affect the transport of ions. A current intensity below the pain threshold that is comfortably tolerated by the patient is passed for an appropriate length of time (usually below 0.5mA/cm²). The current intensity should be gradually increased in the beginning and slowly decreased towards the end. The current can be given in any of the different waveforms, square, sinusoidal, triangular etc. The current density is the current intensity per unit cross sectional area. In practice, the density will vary from point to point and the value calculated would be an average value at the electrode surface. What happens here is, the ions transferred through the skin are taken up by the micro circulation at the epidermodermal junction and the current flows back through the return electrode. If any skin irritation occurs at this stage, the current intensity should be lowered. Various factors affect the intake of drugs by skin like lipophilicity, molecular weight, site, age of patient, drug concentration, the possibility of improving conduction of addition of salts etc.

Iontophoretic electrochemistry³⁴

An iontophoretic device comprises a power source and two electrode compartments Fig. 2. The drug formulate ion (D + A^-) contaning the ionized molecule (D +) is placed in the elect rode compartment bearing the same charge; for example, a positively charged drug such as lidocaine would be placed in the anodal compartment. Although there are many different types of electrode, the most well-suited to iontophoresis is the Ag/AgCl couple^{35 –37 .} First, it avoids the sharp decreases in pH that are seen with, for example, Pt-metal electrodes : Ag/Ag Cl electrodes have the consider able advantage that their electrochemistry occurs at volt ages lower than those necessary for the electrolysis of water, which is undesirable for two reasons: first, the protons created at the anode compete to carry charge and because of their small size and high mobility, they may significantly reduce drug delivery efficiency, and second, the own pH produced in the anodal compartment can lead to acid induced skin burns and it may have an adverse effect on drug stability. Once the current is applied, the electric field imposes a directionality on the movements of the ions present positive charges in the anodal compartment move towards the cathode whereas an ions move in the opposite direction .The electrochemistry occurring at the Ag anode necessitates the presence of Cl^- ions in the anodal compartment: that is requirement usually leads to a decrease in drug delivery efficiency since the NaCl commonly used to provide Cl^- also introduces sig-Fig. 2. Significant concentrations of highly mobile Na⁺ ions which compete very effectively with the drug to carry current. As the Cl^- ions arrive at the electrode –solution interface, they react with the metallic silver to form silver chloride, which on account of its low solubility product, is deposited at the elect rode surface, simultaneously releasing an electron. In order to maintain electro neutrality in the anodal compartment, either a cation must move out of the compartment and into the skin or an anion must leave the skin and move into the anodal chamber. In the cathodal compartment, the AgCl is reduced by the arrival of electrons from the power supply and yields metallic silver to get her with a Cl^– ion, which passes into the solution.

Figure No. 2: Iontophoretic Electrochemistry

Advantages and disadvantages of iontophoresis

These are summarized in Table no.1

Table no.1: Advantages and disadvantages of Iontophoretis

ADVANTAGES

DISADVANTAGES

1. This method minimizes the potential trauma due to injection and the risk of infection associated with it and also avoids the pain and anxiety caused by needle insertion ^38. 2. For local or topical treatment, iontophoretic delivery has the advantage of reduced systemic side effects because only minute amounts of the drug delivered reach the systemic circulation while a high local drug concentration is achieved ^32. 3. Delivery of ionized and unionized drugs^8 4. Enabling continuous or pulsatile delivery of drug (depending on the current applied)^8^.Permitting easier termination of drug delivery^8 5. 5Improving the delivery of polar molecules as well as high molecular weight compounds^8 6. Ability to be used for systemic delivery or local (topical) delivery of drugs^8 7. It maintains controlled plasma levels of drugs, even those with short biological half-lives^39 8. The high energy requirement in iontophoresis for sustained therapeutic delivery influences the size and cost of the dosage form making use less economical.^40

1. The disadvantages include the possibility of electric shock, skin irritation or burns 41,,19,38.^{5} 2. Iontophoresis not recommended for underarm or facial/head hyperhidrosis.^42 3. The metal in the electrode should not be in direct contact with the skin as this can cause the burn^13. 4. Can be lime-consuming to administer^5 5. Lowered efficacy with non polar drags (iontophoresis only)^5 6. Iontophoretic application may be injurious to skin 7. iontophoresis is not recommended for underarm or facial/head hyperhidrosis.^42 8. the high-energy requirement in iontophoresis for sustained therapeutic delivery influences the size and cost of the dosage form making its use less economical.^40

Again, for electroneutrality, this must be compensated for by the arrival of a cation from within the skin into the cathodal chamber or by the loss of an anion. Since the electrical circuit is completed by the endogenous inorganic ions that are present in the skin, primarly Na +and Cl^- these latter species can impact on the efficiency of drug transport.

A. Composition of Formulation

1. Concentration: Concentration of drug is one of the most important factors affecting iontophoretic process. The effect of the concentration has been studied on a number of drugs. An increase in concentration was shown to increase the ap-parent steady state flux of a number of drugs e.g., AVP ⁴³, metoprolol ⁴⁴, butyrate ⁴⁵, diclofenac sodium ⁴⁶, dopamine agonist 5-OH DPAT ⁴⁷, rotigotine ⁴⁸, atenolol HCl ⁴⁹ and ketorolac ⁵⁰. All these drugs showed a propoptional increase in flux with an increase in concentration. With drugs like benzoate ⁵¹ and LHRH ⁵², a modest increase was observed.

Factors influencing iontophoretic drug delivery

These are summarized in

Table No 2: Factors influencing iontophoretic drug delivery

A. Composition of Formulation

Concentration

pH

Ionic strength and presence of other ions

B. Physicochemical Properties

Molecular size and molecular weight:

Charge

Polarity

C. Experimental Conditions

Current strength

Current profile

Pulsed current

Electrode material

D. Regional blood flow

E. Condition of skin

But this is not the general observation since, an increase in concentration increases flux upto a point, after which the flux becomes independent of the donor concentration. This is probably due to the charge saturation of the aqueous conducting pathways of skin also called as boundary layer saturation⁵³. Methyl phenidate showed a little change in flux when concentration was increased be-yond 0.1M ⁵⁴.

2. pH: Since iontophoresis is widely used for peptide delivery, pH plays a vital role and it determines the ionization of peptides, which depends upon isoelectric point and respective pKa of charged amino acid. Moreover, skin permeability is also dependent upon pH e.g., AVP (pI- 10.8) showed maximum flux when donor having a wide range of pH (4-8were used^55,56 but calcitonin (pI-6.5) showed optimum flux at pH 4.0 and not at higher pH ⁵⁷. 5-OH DPAT showed enhanced flux when pH was increased from 3 to 5but not at higher pH ³⁰. In case of leuprolide (LHRH agonist) a two fold increase in flux at pH 7.2 was observed than at pH 4.5⁵⁸. There was a three fold increase in flux obuprenorphine at pH 4.0 than at pH 5.0⁵⁹. Glibenclamide when given by pulsed iontophoresis, showed higher flux apH 8.5 than at pH 7.4 or 8.0 ⁶⁰. Since pH influences the charge on protein, polarity of electrodes is an important factor to be taken into consideration during drug delivery e.g anodal delivery of insulin is preferred ⁶¹ but below its isoelectric point ⁶² whereas in case of pilocarpine a moderate pH of 5.98 is required to achieve maximum permeation⁶³. Thus, the optimum pH for iontophoretic delivery of a compound is one where it exists predominantly in an ionized form. The effect of pH of aqueous vehicle on rate and extent of iontophoretic delivery of lidocaine was investigated. The rate was found to be maximum when the drug was in an ionized form⁶⁴. Thus, pH is an important factor governing the iontophoretic delivery of drugs. Moreover, it also influences the chemical stability of the drug involved^1.

3. Ionic strength and presence of other ions:¹⁰

In iontophoresis the main aim is that the drug ion should carry maximum charge across the membrane. It follows that an increase in ionic strength will decrease drug delivery, as extraneous ions compete with the drug ions. The buffering agents used to maintain pH of the donor medium is a source of co-ions. These co-ions are generally more mobile and smaller in size than the drug ions itself and can dominate the penetration into the skin thereby causing a decrease in transdermal flux of the drug. Many peptides widely studied for ionic strength showed a higher flux occurring at low electrolyte concentration ^43,55. Similarly, drugs like ketorolac showed increased flux with decrease in ionic strength ⁵⁰. A 50% reduction in benzoate flux occurred when an approximately equimolar amount of NaCl was added to donor compartment ⁵².

Physicochemical Properties

1. Molecular size and molecular weight: The molecular size of the solute is a major factor governing its feasibility for iontophoretic delivery and hence the amount transported. When the iontophoretic delivery of carboxylate ions was studied, flux for acetate was found to be more than that of hexanoate and dodecanoate. This suggests that smaller and more hydrophilic ions are transported at a faster rate than larger ions ^66,67. Many studies correlating flux as a function of molecular weight have been conducted and it was concluded that for electro repulsive iontophoresis, when all other conditions were kept constant, transport of compounds decreased with increase in molecular weight (chloride>amino acid>nucleotide>tripeptide>insulin)^68-72. But due to the use of advanced techniques like iontophoresis, electroporation and phonophoresis, delivery of even large molecule like peptides is possible now.

2. Charge: Charge on a molecule is an important physicochemical property governing iontophoretic transport, since the sign of the charge determines the mechanism by which iontophoresis will proceed e.g., electro repulsion or electro repulsion and electro osmosis ⁷⁶. Although the transport of cations has been shown to be better than anions for amino acids and peptides ^{68, 69, 73}, this however is not so simple because an increase in charge will require pH to be decreased, which in turn shall directly decrease the electrosmoss and electro transport process. An increased positive charge on peptide, cause it to bind tightly to the membrane creating a reservoir which in turn can decrease the rate at which the steady state flux will be achieved⁷⁴.

3. Polarity: Generally, the compounds which are hydrophilic are considered ideal candidates for optimum flux e.g. ,nalbuphine and its ester showed an increased flux as the lipophilicity of the compound decreased ⁷⁶.

B. Experimental Conditions

1. Current strength: Since current can easily be controlled by the use of electronics, it is a convenient mean to control delivery of drugs to the body. However, a large increase be-yond the permissible limits causes irritation and can damage the skin. A linear relationship has been observed between the apparent flux of a number of compounds and the applied current. Methyl phenidate showed a linear relationship be-tween the applied current and its iontophoretic flux ³⁷. A linear increase in the flux with current has also been found for TRH ⁷⁷, verapamil ⁷⁸, diclofenac ⁷⁹ and ketorolac ⁵⁰. In general 0.5mA/cm² is often stated to be the maximum iontophoretic current which should be used on human beings ⁸⁰.

2. Current profile: Mostly, in the studies conducted on animals in vitro, current is kept constant and very low voltage of about 10 V is applied.

3. Pulsed current: The persistent use of direct current DC), proportional to time, can reduce the iontophoretic flux because of its polarization effect on the skin ⁸¹. This can be overcome by the use of pulsed DC which is a direct current delivered in a periodic manner ⁸². During “off stage” the skin gets depolarized and returns to the initial polarized state. However, Bagniefski and Burnett showed that enhanced skin depolarization can decrease the efficiency of drug transport, if the frequency of pulsed current is very high ⁸³. A two fold increase in the transdermal flux of vaso-pressin was observed when pulsed current was used in vivo in rabbits ⁸⁴. Enhanced transport of proteins and peptides has been reported using pulsed DC e.g., insulin ⁸⁵. But in many cases like sufentanil ⁸⁶, fentanyl ⁸⁷ and ketorolac ⁵⁰ a decreased flux was observed when pulsed current was used as compared to constant direct current.

4. Electrode material: Iontophoretic studies have been conducted using both platinum wire and Ag/AgCl wires. However, platinum electrodes or other inert electrodes like nickel or stainless steel have been found to cause pH drift and gas bubbling due to decomposition of water and thus causing production of H+ and OH-ions ²⁶ in the following manner:

Anode: H2o +2H+ 1/2 O2 + 2e-

Cathode: H2O + e-OH- + 1/2 H2

Thus, Ag/AgCl electrodes with redox potential lower than that of water which help to maintain electroneutrality at both anode and cathode have been used for this purpose. Phipps et al. ⁸⁸ studied the electrode material selection n optimizing the delivery of lithium across polyvinyl alco-hol (PVA) hydrogel membrane. They showed use of plati-num anode in donor caused a pH decrease due to production of hydronium ion as shown above, which are more mobile and no efficient delivery of lithium was observed while the use of Ag/AgCl electrodes in place caused no pH drift and a significant increase in lithium flux almost double of the above case was observed.

D. Regional blood flow: During iontophoresis, the dermal blood supply determines the systemic and underlying tissue solute absorption. Blood supply however, does not appear to affect the drug penetration fluxes through the epidermis during iontophoretic delivery. Cross and Roberts ⁸⁹ showed that solute in the upper layer of the skin following iontophoresis was comparable in anaesthetized rats and sacrificed rats. It can thus be presumed that the blood did not affect the penetration through the epidermis since the latter has no blood supply.

E. Condition of skin: In iontophoresis, skin condition also affects the penetrating properties of permeant. Roberts et al., studied the in vivo passive diffusion of methyl salicylate using skin from different areas of human body and observed the following rank order: abdomen> forearm> instep> heel> planter, for all subjects⁹⁰. Feldman et al., showed that the passive diffusion ohydrocortisone occured maximally from the area with numerous hair follicle while lesser in area with thickest stratum corneum ⁹¹.

Applications of iontophoresis

1. Antibiotics:

There have been several reports of successful iontophoresis of antibiotics through both injured and intact tissue. Rapperport et al showed that iontophoresis enhanced the transport of penicillin through bum eschar into underlying a vascular tissues, yielding concentrations far exceeding those to which no electric current was applied (200-fold increase). Bactericidal levels of antibiotic were achieved in areas thought to be major sites of the origin of bacteremia and septicemia in patients with bums. Rigano et al examined the effect of gentamicin or penicillin iontophoresis on the management of ear bums in 145 patients. The incidence of ear infection and need for chondrectomy were virtually eliminated by antibiotic iontophoresis.⁵

2. Uses of iontophoresis in neurosciences:

Iontophoresis was also utilized in the neuro physiological studies with the development of a microiontophoresis technique which uses a tiny glass electrode filled with electrolytes ¹⁶⁸. One example of the application is in the controlled ejection of ionized drugs from micropipettes. By using this micro iontophoresis technique, it is possible to study the interactions and effects of drugs on a very restricted area of tissue. This technique has been applied to neuromuscular junction, peripheral and central nervous systems and some smooth muscle preparations ¹⁶⁹. Microiontophoresis has been applied extensively in a wide spectrum of neurophysiologic and neuropharmacologic studies ^92-98.

3. Dermatology

In hyperhidrosis, especially palmar and plantar – probably by obstructing the sweat ducts. No side effects when compared to anti- cholinergics. Copper- iontophoresis for fungal infection and male contraception, zinc for ulcers, iodine for reduction of scar tissues, iron/titanium oxide for tattoo removal. Histamine in allergy testing.

In the diagnosis of cystic fibrosis to increase sweating by pilocarpine and confirm diagnosis by the concentration of sodium and chloride in the sweat.

In scleroderma, for iontophoretic delivery of hyaluronidase.

4. Ophthalmology

Iontophoretic induction of various drugs like atropine, scopolamine, sulfadiazine, fluorescein, gentamycin etc.³³

5. Delivery of antisense oligonucleotides

Antisense oligonucleotides bind to the mRNA of the disease-causing genes and inhibit their expression so as to block synthesis of disease related proteins. These oligonucleotides are usually delivered by injection and hence an alternative route for systemic delivery is desirable. The transdermal delivery route is attractive because it may enable the localized delivery of the oligonucleotide into skin layers, which is desirable in conditions such as dermatitis and psoriasis. IL-10 over-expression for example, is one of the important pathogenic factors in skin lesions resulting from atopic dermatitis (AD). Thus, the regulation of IL-10 production is a potential solution for immunotherapeutic intervention in AD. A study has been conducted by Sakamoto et al. ⁹⁹ which included the topical delivery of an antisense oligonucleotide for mouse IL-10 and the observation of the therapeutic effect on the AD skin lesions of mice. By using iontophoresis the authors were able to deliver 30% of the applied dose locally to the dermis and the epidermis. Topically delivered oligonucleotide decreased the levels of mRNA and protein of IL-10 in the lesions of mice and the dorsal lesions disappeared with repeated topical application. It was concluded that this delivery system offered potential therapy for established dermatitis patients. In addition, a number of studies have demonstrated measurable concentrations of oligonucleotides with in vitro and in vivo delivery ^100,101. However, the question still unanswered is whether an iontophoretic patch of reasonable size and current strength is able to deliver a useful dose of pharmacologically active oligonucleotide ¹⁰². The need currently is for more studies in this area and additional invivo studies to support the in vitro data.⁸

6. Treatment of hyperhydrosis

Hyperhydrosis (also called hyperhidrosis) is a condition that most often results in excessive sweating in the handsand feet. Tap water iontophoresis is one of the most popular treatments used in this condition. The procedure uses a mild electrical current that is passed through tap water to temporarily shut off sweat glands. A hand and foot is each placed in a different water basin and the electric current Is gradually increased to the required level and maintained for 20 min followed by a gradual decrease. The under lying mechanism of how iontophoresis helps treat this ailment is not fully understood. According to one hypothesis, ionto-phoresis may induce hyperkeratosis of the sweat pores and obstruct sweat flow and secretion (although no plugging of the pores has been found)¹⁰³. Other proposed mechanisms include impairment of the electrochemical gradient of sweat secretion and a biofeedback mechanism. Successful induction of hypohidrosis by tap-water iontophoresis requires the application of 15–20 mA to each palm or sole for 30 min per session for 10 consecutive days, followed by one or two maintenance sessions per week .The advantage of using tap water iontophoresis is that the patient can conduct the procedure at home⁸.

CONCLUSION:

Iontophoresis which is a physical approach to transdermal drug delivery can serve as a better alternative to increase the permeability and thereby bioavailability of drug. The significances of iontophoretic delivery system makes its future scope on large scale because of the accurate control over drug input kinetics and optimization of drug input rates. In the future, this system might be used to deliver macromolecules including therapeutic proteins or vaccines transdermally. Thus, iontophoresis may prove to be an important alternative method of drug delivery in the near future after the considerable amount of research and judicious use of technology.

ACKNOWLEDGEMENT:

Author thanks to Principal Mr. D. G. Baheti and Management of college for providing the necessary facilities to carry out the research work.

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Received on 24.07.2013

Modified on 22.08.2013

Accepted on 28.08.2013

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Research Journal of Pharmaceutical Dosage Forms and Technology. 5(6): November-December, 2013, 361-370