Does Phonophoresis Improve Efficacy of Topically Applied Drugs?

Improving drug delivery has been a topic of interest to pharmaceutical researchers in recent years. In particular, researchers are continually investigating methods to improve drug absorption for either localized or systemic effect on the body. While it is important to look for innovative methods to enhance drug penetration, it is imperative that current methodologies used in clinical practice for this same purpose are evaluated.

Phonophoresis refers to the use of ultrasound to introduce a certain drug into the tissue of interest. The medication used as a topical agent can be applied prior to or after an ultrasound application.

The procedure is commonly used with antiinflammatory medications such as dexamethasone and salicylates, as well as with anesthetics such as lidocaine. Physiotherapy clinics utilize this technique; however, it is not only exclusive to this field. The present question remains as to whether this technique is successful in enhancing drug absorption in the body.

One study compared the efficacy of phonophoresis with the nonsteroidal anti-inflammatory drug diclofenac, and conventional ultrasound therapy in primary knee osteoarthritis (OA). In this randomized controlled study, there were significant improvements in most of the clinical parameters (pain, stiffness, and physical functions).

Neither of the methodologies was found to out-perform the other except with respect to one parameter, which was the pain felt by patients while walking. Phonophoresis therapy was found to improve outcomes for patients regarding this parameter in comparison to ultrasound therapy alone. This study raises an interesting question: if phonophoresis with an anti-inflammatory drug and ultrasound therapy produced similar results in alleviating pain symptoms in OA, what is a common mechanism between these two modalities?

Phonophoresis is thought to increase skin permeability by two possible mechanisms: acoustic cavitation and thermal effects of ultrasound. Cavitation causes a rearrangement of the lipid bilayers, which leads to formation of aqueous channels in the skin through which drugs can penetrate into the targeted tissue. It has been demonstrated that the lower the ultrasound frequency, the faster and greater the heating regardless of the depth. Skin permeability is positively correlated with increasing heat, as every 10-degree Celsius increase in temperature leads to a doubling of skin permeability. Another similar study compared the effectiveness of ibuprofen phonophoresis versus ultrasound therapy in knee OA, but came to a similar conclusion that one modality was not superior to the other. Perhaps it is the thermal effects common to both ultrasound and phonophoresis that are largely responsible for increased drug penetration. However, these studies regarding phonophoresis remain inconclusive and require further research into the efficacy of this technique.

References:

Sreeraj, S.R., Bellare, B., & Ray,I. A Review on Ultrasound Parameters and Methods of Application in Transdermal Drug Delivery. International Journal of Health Sciences and Research. (2015). https://www.ejmanager.com/mnstemps/107/107-1430918845.pdf
Okatyoglu, p., Gur, Al. Yardimeden, I., Caglayan, M, Cevik, F. Bozkurti, M, Em, S., Ucar, D, Nasi, K. Comparison of the Efficacy of Phonophoresis and Conventional Ultrasound Therapy in Patients with Primary Knee Osteoarthritis. Ericyes Med. J. (2014). http://www.erciyesmedj. com/sayilar/240/buyuk/EMJ%20t%C3%BCm%C3%BC.pdf#page=21