There are several common methods that clinicians use to administer medication. One method which has been gaining in popularity is the delivery of medication transdermally. Inherent advantages to this method includes the ability to use a wide array of compounds—having either analgesic or anti-inflammatory actions—applied directly into the target area. This allows for a smaller dose of medication to be used than would be required with other routes of administration. This smaller amount of medication translates into a decreased chance of adverse drug side effects— always a desirable outcome.

This article will focus on iontophoresis, a form of transdermal drug delivery (TDD) that utilizes electrical current to drive or push ionized drugs through the skin’s outermost layer (stratum corneum) which is typically the main barrier to drug transport. Using the rule of ‘likes repel,’ the practitioner chooses medications compatible with the active pole being used so that a positively charged drug is loaded into the positive side of the delivery pad or electrode. Since like charges repel, the positively charged molecules are driven through the skin by the positive current, while negatively charged medications are driven in under the negative pole. Once the drug passes through the skin barrier, natural diffusion and local circulation (perfusion) take over and ultimately determine how the drug is distributed.

Common Uses for Iontophoresis

In rehabilitation medicine, including physical therapy, iontophoresis is used to reduce inflammation that might be seen in musculoskeletal conditions such as lateral epicondylitis, medial epicondylitis, plantar fasciitis, tendo-nitis/bursitis, rheumatoid arthritis, and enthesopathic conditions of various origins. The most popular and well researched iontophoresis application is the use of dexamethasone, a corticosteroid in a sodium phosphate solution. In this form, the drug is composed of negatively charged ions of dexamethasone phosphate and, when loaded into a negatively charged reservoir or electrode pad, the electrical force of the like charges pushes the medication molecules into the desired area. There are two commonly used ways of applying iontophoresis; the first is the traditional method of using a current generator with lead wires connected to an active pad and a dispersive pad (see Figure 1). The medication is loaded in the active pad usually by syringe. The dispersive pad is the polar opposite pad and located away from the treatment site. The treatment is administered clinically for 15-20 minutes per session. In a physical therapy setting, iontophoresis is typically one of several treatment interventions applied, so the addition of another 15-20 minutes to a pre-existing 60 minute program is a time burden for some patients. One ionto-phoresis manufacturer has responded to this situation by introducing a more mobile solution to iontophoresis treatment—sold under the brand name of IontoPatch®—that may be worn by the patient for a 24-hour period. In this way, the clinical time component of this treatment is eliminated altogether and the patient gets a more sustained 24 hour effect. These mobile IontoPatches contain a small flat battery that provides a tiny electrical “push” of the target medication (e.g., dexamethasone; see Figure 2).

The dose period recommended for iontophoresis is calculated based on the amount of current that is flowing, together with the elapsed time of treatment. The dose is expressed as milliampere minutes (mA-min) with the recommended milliampere-minute dose depending on the electrode used. For most electrodes being used today, a typical dosage is 40 mA-min and which can be delivered in a number of ways as long as the product of the two terms equals 40 (e.g., 4 mA x 10 minutes or 2 mA x 20 minutes, etc). The current setting is chosen based on patient comfort and, once the amount of current is determined, the current generator selects the appropriate amount of time required to achieve the pre-set mA-min dose. When using mobile patches, a microampere current is used for much longer periods of time.

Electrode patches have a unique composition that allows ionic movement into human skin tissue. One patch, for example, is made up of embedded zinc and silver chloride electrodes and is activated when the treatment solution bathing one electrode comes into contact with the saline solution bathing the opposite electrode. This creates the necessary charge to drive the molecules into the target tissues. The patches are made up of a semipermeable adhesive membrane that must be in close contact with the skin for optimal penetration.

Iontophoresis for Inflammation

There are a number of drugs that can be driven into the subcutaneous tissues including steroids, NSAIDS, local anesthetics, salicylates, and individual substances such as zinc oxide, iodine, acetic acid, and calcium chloride, to name a few. For a listing of the most commonly used drugs and their applications please refer to Table 1. It is thought that dexamethasone (DEX) can be driven up to 20mm into the tissues with tissue concentration decreasing exponentially with tissue depth. Other factors have been recently identified as being determinants of drug delivery including ratio of skin pore size to drug molecule size, polarity, and the importance of the electric field strength.¹ Research indicates that increasing the current density under the membrane can only contribute so much to the total absorption of a specific drug molecule, with passive solvent flow being responsible for a significant portion of the total absorbed amount.² The more superficial a target structure is, the more drug will be made available for interaction. Conversely the deeper a structure is, the less likely there will be a therapeutic interaction since the drug becomes more diluted as the distance between the electrode and target tissue increases. This makes iontophoresis preferable for treating superficial soft tissue structures.

Corticosteroids are the primary drugs used with iontophoresis in physical therapy and rehabilitation medicine in general. Formulated as a water soluble salt, the corticosteroid molecule has a negative charge and so the negative-electrode drug reservoir must be used. In applying an iontophoresis treatment the area to be treated must be cleaned or prepped with alcohol then the active electrode placed as close to the target area as possible. As with all drug therapies, the clinician should review possible contraindications and adverse effects with the patient prior to commencing treatment. Also, it is important to check the treatment area to make sure the skin is intact and not broken. The other electrode is placed 4-6 inches away when using the electric generator unit type (having leads and electrodes). When using the IontoPatch, the electrode distance is preset and not a factor. The clinician then sets the desired electrical dose (in mA-min) at a level that is comfortable for the patient. While it is typical to have some erythema at the electrode sites after a treatment session, the skin should be inspected after a treatment to ensure no burning has occurred. It is not recommended that simultaneous heat or ice be applied over both electrode and skin since both of these will significantly alter blood flow and skin sensitivity levels—both of which need to be at normal levels for safe treatment. This applies to both the clinical and take home (IontoPatch) versions of this treatment. Similar precautions to transdermal drug delivery of opiod medication, such as the Fentanyl patch, should be observed—specifically relating to the application of heat or cold to the patch. Unlike prescription medication TDD, the use of iontophoresis has not been shown to interfere with concomitant use of other systemic medications. One of the advantages of iontophoretically-administered drugs is that the medication is delivered locally and not systemically, so adverse drug reactions and interactions are minimized. Using iontophoresis, the amount of medication required to reduce inflammation in a given area is much less than would be required with oral administration.

Calcific Deposits

There has been much debate recently regarding the efficacy of iontophoretically-delivered acetic acid (vinegar) in conditions such as calcific supraspinatus tendonitis (CST). This condition is essentially the deposition of calcium crystals within the substance matrix of the common rotator cuff tendon. Ultrasonography and MRI have been used to detect these calcium carbonate deposits. For many years, it has been postulated that the application of acetic acid to the affected tissue may have a beneficial effect on this condition via the conversion of calcium carbonate to calcium citrate, a much more soluble compound that is more readily absorbable by local blood circulation. The validity of this assertion continues to be a researchable topic, as well as the assertion that calcific deposits are necessarily the cause of shoulder pain. Research, however, suggests that this is not always the case.³⁻⁵

Table 1. Iontophoresis Cross-reference
Drug Charge +/- Condition
Acetic acid Negative Calcium deposits
Chloride Negative Scar tissue
Dexamethasone Negative Inflammation-tendonitis/bursitis
Calcium Positive Muscle spasm/muscle dysfunction
Hydrocortisone Positive Anti-inflammatory steroid/myositis
Zinc oxide Positive Antiseptic/wound healing
Salicylates Negative Arthralgia/myalgia
Lidocaine Positive Tenosynovitis
Atropine sulphate Positive Hyperhydrosis
Magnesium Positive Muscle relaxant
Zinc oxide Positive Wound healing/antiseptic

The incidence of rotator cuff calcification without shoulder symptoms in the general population is 3-20% according to different reports. The highest incidence is in adults aged between 30-50 years old. The overall incidence of calcific tendinitis appears to have declined in the last few decades. The epidemiology of the condition seems to favor women more than men, and is more often seen in the dominant shoulder. The appearance of the deposits is usually one to two cm proximal to the rotator cuff insertion at the greater tuberosity of the humerus. Nonsurgical treatment remains the standard of care and reports show that conservative methods such as ultrasound, cold laser, iontophoresis, phonophoresis and therapeutic exercise applications can eventually lead to full restoration of function.⁶

Conclusion

Iontophoresis is an effective and well tolerated method for delivering ionized medications through the dermis using a controlled amount of electrical current. This mode of treatment offers benefits to a wide array of musculoskeletal disorders. In physical therapy, the use of dexamethasone for inflammation and acetic acid for calcific deposits has been used for many years in numerous clinical settings. Iontophoresis, in conjunction with other conservative therapies and interventions, has been shown to effectively manage painful symptoms associated with superficial tissue structures in a wide variety of patients.