Transdermal, with enhanced skin permeability

Transdermal Drug Delivery System with Enhanced Skin Permeability... 

Ultrasound may enhance transdermal transport by inducing skin alteration and active transport (forced convention) in the skin. Various other means of transport enhancement, including chemicals, iontophoresis and electroporation, may enhance transport synergis-tically with US. Thus, the evaluation of the synergistic effect of low-frequency US with chemical enhancers and surfactants for permeation of mannitol revealed that application of US or sodium lauryl sulfate (SLS) alone, both for 90 min, increased skin permeability about 8 and 3 times, respectively. However, the combined use of US and a 1% SLS solution increased the skin permeability 200 times to mannitol [129]. 

In a recent systematic study of the dependence of 20 kHz sonophoresis on ultrasound parameters, Mitragotri et al. showed that the enhancement of skin permeability varies linearly with ultrasound intensity and ultrasound on-time (for pulsed ultrasound, ultrasound on-time equals the product of total ultrasound application time and duty cycle), while is independent of the ultrasound duty cycle. Based on those findings, fhe authors reported that there is a threshold energy dose for ultrasound induced transdermal drug transport. Once the threshold value is crossed, the enhancement of skin permeability varies linearly with the ultrasound energy dose (J/cm ), which is calculated as the product of ultrasound intensity and ultrasound on-time. This result indicates that ultrasound energy dose can be used as a predictor of the effect of 20 kHz sonophoresis. The authors also indicated that it is important to determine the threshold energy dose for each individual sonophoresis system, for example, the real in vivo situation, because it may vary from system to system. Specifically, it may vary between different skin models, as well as with the ultrasound frequency and the distance of the transducer from the skin surface, etc. 

Because of the low permeability of the skin to many drugs, trans-dermal delivery has limited applications. The low permeability is attributed primarily to the stratum comeum, the outermost skin layer which consists of flat, dead cells filled with keratin fibers surrounded by lipid bilayers. One common method of increasing the passive transdermal diffusional drug flux involves pretreating the skin with a skin permeation enhancer. 

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