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Journal of clinical pharmacology and therapeutics

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Accordingly, if one idenjpgies the dominant phenomena responsible for sonophoresis, a better selection of ultrasound parameters and surrounding physiochemical conditions journal of clinical pharmacology and therapeutics be made to selectively enhance the favourable phenomena, thereby broadening the types of drugs that can be administered transdermally (15).

In order to understand the mechanisms of sonophoresis, it is important to idenjpgy various effects of ultrasound exposure on human tissue since one or more this effects may contribute to the mechanism of sonophoresis.

Cavitation involves the generation and oscillation of gaseous bubbles 30 mg a liquid medium and their subsequent collapse when such a medium is exposed to a sound wave, which may be an ultrasound. It can generate violent microstreams, which increase the bioavailability of the drugs (16).

Cavitation occurs due to the nucleation of small gaseous cavities during the negative pressure cycles of ultrasound, followed by the growth of these bubbles throughout subsequent pressure cycles.

Whenever small gaseous nuclei already exist journal of clinical pharmacology and therapeutics a medium, cavitation takes place preferentially at those nuclei (15,17). This cavitation leads to the disordering of the lipid bilayers and formation of aqueous channels in the skin through which drugs can permeate (18,19,20). The minimum ultrasound intensity required for the onset of cavitation, referred to as cavitation threshold, increases rapidly with ultrasound frequency (16,18).

But as cavitational effects vary inversely with ultrasound frequency, it was found that any frequency lower than that corresponding to therapeutic ultrasound was more effective in enhancing transdermal transport. This is a direct consequence of reduced acoustic cavitation (formation, growth, and collapse of gas bubbles) at high ultrasound frequencies.

Application of ultrasound generates oscillating pressures in liquids and nucleates cavitation bubbles. At higher frequencies it becomes increasingly difficult to generate cavitation due dosage the fact that the time between the positive and negative acoustic pressures becomes too short, diminishing the ability of dissolved gas within the medium to diffuse into the cavitation nuclei.

The number and size of cavitation bubbles is inversely correlated with application frequency (21, 23). Cavitation occurs in a variety of mammalian tissues, including muscle, brain and liver, upon exposure to ultrasound in different conditions.

This occurrence of cavita-tion in biological tissue is attributed to the existence of a large number of gas nuclei. These nuclei are gas pockets trapped in either intracellular or intercellular structures. It has been shown that cavitation inside the skin plays a dominant role in enhancing transdermal transport upon ultrasound exposure (15). Cavitation inside the SC can potentially take place in the keratinocytes or in the lipid regions or in both. Since the effect of ultrasound on transdermal transport depends strongly on the dissolved journal of clinical pharmacology and therapeutics content in the surrounding buffer and because most of the water in the SC is present in the keratinocytes, it can be said journal of clinical pharmacology and therapeutics cavitation inside the SC takes place in the keratinocytes (Fig.

Oscillations of the ultrasound-induced cavitation bubbles near the keratinocyte-lipid bilayer interfaces may, in turn cause oscillations in the lipid bilayers, thereby causing structural disorder of the SC lipids. Shock waves generated by the collapse of cavitation bubbles journal of clinical pharmacology and therapeutics the interfaces may also contribute to the structure disordering effect.

Because the diffusion of permeants through a disordered bilayer phase can be significantly faster than that through a normal bilayer, transdermal transport in the presence of ultrasound is higher than passive transport. This, prognosis essence, is the mechanism of sonophoresis. Cavitation in the saline surrounding the skin does occur after ultrasound exposure. These cavitation bubbles can potentially play a role in the observed transdermal transport enhancement.

Firstly, these bubbles cause skin erosion, following their violent collapse on the skin surface, due to generation of shock waves, journal of clinical pharmacology and therapeutics enhancing transdermal transport.

Secondly, the oscillations and collapse of cavitation bubbles also cause generation of velocity jets at the skin-donor solution interface, referred to as microstreaming.

These induce convective transport across the skin, thereby enhancing the overall transdermal transport. Experimental findings suggest that cavita-tion outside the skin does not play that important a role in sonophoresis (11,15). The increase in the skin temperature resulting from the absorbance of ultrasound energy may increase the skin permeability coefficient because of an increase in the permeant diffusion coefficient. The absorption coefficient of a medium increases proportionally with the ultrasound frequency, indicating that the thermal effects journal of clinical pharmacology and therapeutics ultrasound are proportional to the ultrasound frequency.

The increase in the temperature of a medium upon ultrasound exposure at a given frequency varies proportionally with the ultrasound intensity and exposure time. The thermal effects can be substantially reduced by pulsed application. Fluid velocities johnson 60 generated in porous medium exposed to ultrasound due to interference of the incident and reflected ultrasound waves in the diffusion cell and oscillations of the cavitation bubbles.

Fluid velocities generated in this way may affect journal of clinical pharmacology and therapeutics transport by inducing convective transport of the permeant across the skin, especially through hair follicles and sweat ducts.

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