The Big Finalé

Bloggers, time has come to delve into our own opinions and really enlighten you on whether iontophoresis is a suitable option for your business plan. As we can see by Belanger; Iontophoresis is a viable option for many different pathology presentations in your clinic including; pain, myopathy, myositis ossificans, tendonitis and epicondylitis. Although we highlighted a few safety parameters in a previous blog, the majority of these may be overcome with care and precision during your application. The science behind iontophoresis has been studied since 1747 and we now must take this delivery system seriously.

If cost is now your only deterrent, you needn’t worry. We have recently been informed by a well-respected physiotherapist who quotes the price of Iontophoresis at $16.22 per dose. Included in this quoted price is the RRP for the packet of two drugs he uses (Dexa and Lignocaine) at $152.30 and $47.90 respectively and the electrodes ($149 for 12). However the initial up front cost for the machine was quoted at $469.10. This initial outlay for the machine may be overcome, as Iontophoresis is a long term, reliable method of drug delivery and its support will only grow as time passes.

There we have it bloggers, we hope that we have informed you about everything Iontophoretic. If you have any further questions don’t hesitate to reply to our blogs.

For and Against

To Iontophorise or not to Iontophorise? That is the question

Holler to the blogosphere! After previously discussing the history, dosage and safety topics, the literature that has evaluated iontophoresis must now be reviewed. The pros and cons will be discussed from a range of papers on iontophoretic drug delivery.

For

First we will look at the merits of iontophoresis. The fact that it is a non-invasive technique is beneficial in terms of patients that are trypanophobic (have a phobia of needles) and need their analgesic delivered to treat the source of pain. Several papers compared Iontophoresis to traditional transdermal delivery system (TDDS) without electrical stimulation. Bodde, Verhoef & Ponec (1989) measured the half-life of a peptide drug in plasma and in the dermis and epidermis. The study showed that the half-life of the drug was significantly longer in the epidermis and dermis than in plasma. Therefore by enhancing the flux through iontophoresis there will be increased drug delivery and the bioavailability of the drug will be higher. The use of the electrical gradient instead of the chemical gradient to drive the flux across the stratum corneum also has its merits according to the same study. The chemical gradient requires higher concentrations of the drug to create a stronger gradient. This is in contrast to iontophoresis that can deliver smaller quantities just as fast but without the side effects that may occur with overdosing of the drug. Bodde et al. (1989) also found that the absorption rate of drugs varied without current application (due to changes in the concentration gradient over time) but this variation did not occur in iontophoresis. The faster diffusion rate of ionized drugs with iontophoresis when compared to TDDS (limited by the chemical gradient) was supported by Srinivasan, Higuchi, Sims, Ghanem & Behl (1989).

Against

Iontophoresis obviously has some great advantages on other drug delivery systems, however there is literature that highlights the limitations of this technique. Sanderson, de Riel & Dixon (1989) brings to light that iontophoresis may be a good system for applications requiring a short period of drug delivery, but has unwanted side effects for applications requiring continuous or long time periods of delivery. These effects were examined in the study of Singh, Gross, Sage, Davis & Maibach (2000), which observed skin irritation in all subjects from four ethnic groups who were treated with saline iontophoresis for four hours. In the Moliton & Fernandez (1939) review of iontophoresis, burns caused by iontophoresis are discussed. However, this is only when a DC current is applied. In this situation hydrogen ions build up in the anode whilst hydroxide ions accumulate in the cathode causing pH changes that lead to electrochemical burns (Howard, Drake & Kellogg, 1995). Howard et al. hypothesized that when an alternating current is applied, hydrogen ions and hydroxide ions will be generated at alternate phases, avoiding the pH change which causes skin burns. Howard’s study observed that no burns occurred on patients for a two or four hour treatment time, so burns need not be caused by iontophoresis. There have been related reports of pain due to iontophoresis mentioned in literature (Khan et al., 2011) but there is no evidence to support these claims.

As you can see, iontophoresis has significant evidence to suggest it is a safe, viable method of drug delivery in situations requiring brief treatment times.

Until next time, you stay classy planet Earth.

References

Singh, J., Gross, M., Sage, B., Davis, H. & Maibach, H. (2000). Effect of saline iontophoresis on skin barrier function and cutaneous irritation in four ethnic groups. Food Chem Toxiology, 38(8), 717-726.

Khan, A., Yasir, M., Asif, M., Chauhan, I., Singh, A., Sharma, R., Singh, P. & Rai, S. (2011). Iontophoretic drug delivery: History and applications. Journal of Applied Pharmaceutical Science, 1(3), 11-14.

Bodde, H., Verhoef, J. & Ponec, M. (1989). Transdermal Peptide Delivery. Biochemical Society Transactions, 17(5), 943-945.

Srinivasan, V., Higuchi, W., Sims, S., Ghanem, A. & Behl, C. (1989). Transdermal iontophoretic drug delivery: mechanistic analysis and application to polypeptide delivery. Journal of Pharmaceutical Science, 78(5), 370-375.

Sanderson, J., de Riel, S. & Dixon, R. (1989). Iontophoretic delivery of nonpeptide drugs: formulation optimization for maximum skin permeability. Journal of Pharmaceutical Science, 78(5), 361-364.

Howard, J., Drake, T. & Kellogg, D. (1995). Effects of Alternating Current Iontophoresis on Drug Delivery. Archives of Physical Medicine and Rehabilitation, 76(1), 463-466.

Moliton, H. & Fernandez, L. (1939). Experimental studies on the causes and prevention of iontophoretic burns. The American Journal of the Medical Sciences, 198(6), 778-784.

A sample case: Epicondylitis

Greetings followers! Let’s have a little look at a specific case study a common musculoskeletal condition. Tennis elbow is the most common condition of the elbow in adults and as seen in the proceeding study can be significantly improved through the use of iontophoresis.

Method:

·         18-75 yrs old clinical signs leading to la dx of medial or lateral epicondylitis

·         patients were randomized into one of two groups: dermal inotophoretic administration of of dexamethasone sodium phosphate 0.4% injection or dermal inotophorectic administration of bacteriostatic sodium chloride injection 0.9%

·         2.5ml of each solution was administered using IOMED phoresor inotophorectic drug delivery system. Solution was instilled into a gel sponge pad

·         40mA-minutes treatment spaced 1 to 3 days apart six treatments completed within 15 day period

Results:


FIGURE 1: Summary of efficacy results by length of time in which patients completed treatments. VAS, visual analog scale score.



·         Patients receiving dexamethasone significantly improved in their visual analog scale score

·         Forty-eight percent of the dexamethasone group and 41% of the placebo group had a score of moderate or better for the patient global evaluation of improvement

·        Patients who completed all six treatments in 10 days or less showed better results than did patients who completed all six treatments over a longer period

Discussion:

The patient’s receiving six iontophoresis treatments of 40mA-minutes were effective in reducing symptoms of medial or lateral epicondylitis particularly when treatments were completed in 10 days or less. Due to no restrictions from using other treatment modalities throughout the trial patients may have also been administering anti-inflammatory medication, steroidal injections or therapeutic exercise which could have altered assessment of symptoms compared to the sole use of iontophoresis.

Still to come are what we are convinced to be the most significant pros and cons of iontophoresis…… Stay tuned!

REFERENCE

Nirschl, R., Rodin, D., Ochiai D. & Maartmann-Moe, C. (2003). Iontophoretic Administration of Dexamethasone Sodium Phosphate for Acute Epicondylitis. The American Journal of Sports Medicine, 31(2), 189-195.

Safety is paramount

Hello Bloggers, now that the dosage guidelines have been discussed, a very important topic to cover is the safety issues. We must take extreme caution when applying iontophoresis because the adverse effects can be severe and permanent. Before the application you must inform your patient about the risks and precautions of iontophoresis.

During your consultation, it is imperative you find out if the patient has any of the usual contraindications for e-stim. However additional contraindications do exist for iontophoresis and a few are outlined here for you. The direct current involved in iontophoresis may cause adverse vision effects when the electrodes are placed over the temporal or orbicular region, thus a different approach for drug administration must be taken when the condition is around these areas (Belanger, 2010). It is also an absolute contraindication if the patient is hypersensitive or allergic to the therapeutic ion being discussed.

The main safety precaution that must be dealt with and thus calculated before the application of iontophoresis is current density (CD). CD is the amount of current amplitude applied against the electrode conductive surface area. The CD limit differs depending on whether the administration is via the cathode, 0.5 mA/cm², or the anode, 1.0 mA/cm²  (Belanger, 2010). The discrepancies between the cathode and anode guidelines are due to the migration of positive ions at the cathode resulting in an alkalitic reaction, leading to an increased risk of chemical burn (Mcgraw Hill). As the process of drug admission is hypothesized to occur through sweat pores and hair follicles (Robertson, Ward, Low & Reed, 2006), CD may be inadvertently increased if the electrodes are placed over an area with low pore density. If the CD exceeds what the skin can withstand; tingling or painful sensations in the entire limb; erythema; skin necrosis; and chemical or thermal burns may occur (Batheja, Kaushik, Hu & Michniak-Kohn, 2007). However, if you exceed this limit by a substantial margin, more serious permanent damage to skin pigmentation may be the outcome.  

A feature of iontophoresis that has been observed and discussed is that skin resistance reduces after 10 minutes of 0.16mA current (Gazelius). Thus increasing application time, and conversely reducing current amplitude, is associated with its own risks for skin irritation. Although this is not within our control, we should make sure that our application is within the safe limits.

Now that we have discussed safety in application, next we’ll endeavor to describe the process of electrode positioning and application.

 REFERENCES:

Batheja, P., Kaushik, D., Hu, L., & Michniak-Kohn, B. (2007). Transdermal Iontophoresis. Touch Briefings, 46-48.

Belanger, A. (2010). Therapeutic Electrophysical Agents: Evidence Based Practice. (2^nd ed.) Wolters Kluwer Health: Lippincott Williams & Wilkins.

Gazelius, B. (n.d.) Periflux Systems, Iontophoresis. PeriMed.

McGraw Hill Higher Education. (2011). Department of Physical Education and Exercise Science. Retrieved March, 20, 2012 from <http://catalogs.mhhe.com>

The dosage parameters....

What’s the dose?

Four parameters:

http://www.transcu.com/en/images/image02_1_2.jpg

·       The selection of drug ions- based on the therapeutic effect that is desired for any given pathology. For example when goals are to decrease pain or inflammation then the drugs selected will be either analgesic and/or anti-inflammatory.

·         Polarity of the aqueous solution of the drug being used- for transport to occur at the electrode/skin interface the negatively charged drug ion must be positioned under the negative pole (cathode). Similarly the positively charged drug ions must be placed under the positive pole (anode). Tap water has a double polarity therefore positioning is not critical however it is recommended to inverse the current midway through treatment to ensure equal phoresis of both ions in the skin.

·         Chemical concentration and volume of ionic drug solution delivered- literary consensus that the concentration range from 2-5% aqueous solution. The solution of the drug should contain low concentrations as it has been found that the amount of drug delivered is not increased with the use of higher concentrations. The volume of drug aqueous solution contained in the electrode patch are dependent on the filling capacity of the individual reservoir and is indicated by the manufacturer

·         The dose used (D)- proportional to the current magnitude used (A) and the total application duration (T)

o   D (mA.min)= A (mA) X T (min)

Drug doses range between 1 and 80 mA.min with a maximum available current amplitude of 4mA. These are delivered using portable stimulators and wearable patches.

·         Portable stimulators- constant current (CC) stimulators maximum DC amplitude reaches 4 mA. Practitioners are able to program the dosage and set the desired amplitude where duration can be manually or automatically controlled.

·         Patches- constant voltage sold either 40 mA.min or 80 mA.min worn for 12hrs and 24hrs respectively. These differences account for current fluctuations due to soft tissue impedance changes; however with the use of patches the practitioner has no control over the amplitude settings.

http://www.ptstuff.com/iontophoresis_electrodes.html

In our next blog we will discuss the safety parameters before the application of iontophoresis within your clinic.


REFERENCES
Belanger, A. (2010). Therapeutic Electrophysical Agents: Evidence Behind Practice (Second Ed.) Philadelphia, PA: Lippincott, Williams and Wilkins.

Iontophoresis: An Introduction and History

An Introduction to Iontophoresis

Iontophoresis, or “electrically assisted transdermal drug delivery” is a method of delivery of ionic substances through the skin, which is assisted or enhanced with an electric charge. This current being delivered can be turned on and off hereby controlling the release of solutes through the skin. Iontophoresis is used by physiotherapists for the delivery of anti-inflammatory medication for the treatment of plantar fasciitis, bursitis and a plethora of other clinical indications (Khan et al, 2011). The substance being transferred through the skin enters the circulation through the capillaries. This is beneficial for administration of some drugs as it avoids first pass clearance by the liver, enzymes and acidic or basic substances in the gastrointestinal tract (Khan et al, 2011). Currently, handheld devices are popular for Iontophoresis treatment (see Figure 1).

Figure 1: Chattanooga Ionto Device (Chattanooga Ionto Device, n.d.).

In terms of the popularity of Iontophoresis, few drugs are delivered this way in comparison to other routes. However, its use is increasing at a projected rate of 12% per annum, with 35 active ingredients approved by the Food and Drug Administration in the United States and 16 active ingredients approved for use worldwide. In 2005, Iontophoresis had a market of $12.7B and this is projected to increase substantially to $31.5B by 2015 (Prausnitz, Mitragotri & Langer 2004).

History

Although currently the use of Iontophoresis is rapidly becoming widespread, the  technique has been centuries in the making. The first notable literature published was in 1747 by Giovanni Pivati. After applying an electric current to a scented plant in a sealed jar, the smell penetrated the container. It was not until the 1850’s when it was first suggested that the application of electric current could be used for medication delivery (Helmstadter, 2001). From that time, several different substances were experimented with for their affinity for transdermal delivery (see Table 1).

(Helmstadter, 2001)

Transdermal delivery of ionized drugs without the aid of electric current had previously been rarely used due to the slow rate of diffusion powered only by the concentration gradient. With the application of the current techniques of Iontophoresis, transdermal delivery of these drugs is now desirable (Wang et al., 2005).

A safe, reliable method of Iontophoresis was first introduced in the US in 1989, however was never successful. Since then, technology has caught up, with the development of new products entering the market and making the process compatible with more drugs, and broadening the clinical indications for use.

Principles of Iontophoresis

Iontophoresis involves two electrodes, the cathode and the anode (see Figure 2). For a drug that is negatively charged, the drug must be dissolved in a solution and loaded into the cathode (negatively charged electrode). This electrode should be placed directly over the lesion and the anode is then placed a few centimetres away on the skin (Khan et al., 2011). As the drug and the electrode in which it is loaded have a like charge, the drug will move through the stratum corneum (the outer layer of the epidermis) towards the anode. Drugs with neither a positive nor negative charge also move through the skin due to osmotic/electro-osmotic forces when a current is applied (Khan et al., 2011). 

Figure 2: Electrode placement and drug delivery (TCT Summary, n.d.).

The history has been covered in todays blog, next up we will discuss the dosage guidelines that need to be understood and adhered to during administration of iontohphoresis.

References

Wang, Y., Thakur, R., Fan, Q. & Michniak, B. (2005). Transdermal iontophoresis: combination strategies to improve transdermal iontophoretic drug delivery. European Journal of Pharmaceutics and Biopharmaceutics, 60(2), 179-191.

Chattanooga Ionto Device [Image] (n.d.). Retrieved from http://www.medicalsearch.com.au/Products/Chattanooga-Ionto-Device-47714

Khan, A., Yasir, M., Asif, M., Chauhan, I., Singh, A., Sharma, R., Singh, P., Rai, S. (2011). Iontophoretic drug delivery: history and applications. Journal of applied pharmaceutical science, 1(3), 11-24.

TCT Summary [Image] (n.d.). Retrieved from http://www.transcu.com/en/p02_1.html

Helmstadter, A. (2001). The history of electrically-assisted transdermal drug delivery. Pharmazie, 56(7), 583-587.

Prausnitz, M., Mitragotri, S. & Langer, R. (2004). Current status and future potential of transdermal drug delivery. Drug Discovery, 3(2), 115-124.