ABSTRACT
Healthy young adults typically can hear sounds between the frequencies of 40 Hz to 20,000 Hz (20 kHz). Ultrasound consists of cyclic sound pressure waves produced above this frequency (i.e., >20 kHz). Ultrasound is typically classi•ed based on frequency as (1) high-frequency or diagnostic ultrasound (above 3 MHz), (2) medium-frequency or therapeutic ultrasound (1 to 3 MHz), and (3) low-frequency or power ultrasound (20 to 100 kHz). High-frequency ultrasound has well-known applications for clinical imaging such as in sonography for fetal imaging. Use of high-frequency ultrasound has also been reported for drug delivery applications (1). Medium-frequency or therapeutic ultrasound has been used for drug delivery in physical therapy clinics. At these frequencies, ultrasonic energy is more readily absorbed by tissue; therefore, a local heating effect often accompanies treatment, which can possibly offer some relief to patients with muscle soreness and related conditions even in the absence of any drug molecule. The temperature can rise by a few degrees Celsius and may also be directly responsible for the increased percutaneous absorption. Therapeutic ultrasound has been reported to have its primary effect on the diffusion coef•cient of the drug rather than on its partition coef•cient (2). Low-frequency ultrasound (LFU) uses frequencies in the range of 20 to 100 kHz and is now being recognized as being the most ef•cient for transdermal delivery applications (3-5). This is believed to be due to the cavitation that occurs at these frequencies. Sonophoresis or phonophoresis is the use of ultrasound to increase the permeation of drugs into or through the skin. Frequencies in the range of 20 kHz to 16 MHz have been investigated for this purpose. The drug may be delivered simultaneously while ultrasound is being applied, or the skin may be pretreated with ultrasound followed by application of the drug (5-8).
