Skin-permeation-enhancing transdermal drug

Cevc G. Transfersomes, liposomes and other lipid suspensions on the skin permeation enhancement, vesicle penetration, and transdermal drug delivery. Crit Rev Ther Drug... 

A new generation of transdermal drug delivery (TDD) system was developed to contain one or more skin permeation enhancers in the surface adhesive coating layers. This TDD system has been found, experimentally, to release the enhancers to the surface of stratum corneum to modify the skin s barrier properties, prior to the controlled delivery of the active drug. The extent of enhancement in skin permeability appears to be dependent upon the chemical structure of drug to be delivered transdermally as well as the type and the concentration of enhancer used. The mechanism of skin permeation enhancement have been explored and are analyzed in this report. 

This new type of transdermal drug delivery system is capable of releasing one or a combination of two or more skin permeation enhancers to the stratum corneum surface in order to modify the skin s barrier properties (10), prior to the controlled delivery... 

Dermac SR-38 is one of a series of oxazolidinones, cyclic urethane compounds, evaluated as transdermal enhancers. The compound was designed to mimic natural skin lipids (such as ceramides), to be nonirritating, and to be rapidly cleared from the systemic circulation following absorption. In animal and human safety studies, Dermac SR-38 demonstrated a good skin tolerance (no observed irritancy or sensitization at levels of 1-10 wt% moderate to severe irritation in rabbit at 100%), and a low degree of acute toxicity (LD50(rat oral) > 5.0g/kg). The compound was evaluated for its ability to enhance the human skin permeation of diverse drugs from dermal and transdermal delivery systems. Data for minoxidil indicated an enhancer concentration-dependent effect for permeation enhancement. Dermac SR-38 was also found to enhance the skin retention of both retinoic acid when applied in Retin A cream, and dihydroxyacetone when applied in a hydrophilic cream. ... 

Figure 12.4 Skin permeation enhancement by pectin and microwave for transdermal drug delivery.

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. 

The lack of significant impact of CPEs on transdermal delivery vehicles is related to the inherent nonspecific activity of CPEs in the different strata of the skin, as discussed earlier. This limitation may be overcome by utilization of mixtures of CPEs. Research has already shown that binary mixtures of CPEs provide increased permeation enhancement as well as increased safety compared to single enhancers. Such unique chemical combinations, called synergistic combinations of penetration enhancers or SCOPE formulations, offer new opportunities in transdermal drug delivery (46). 

Azone (laurocapram) is used extensively as a transdermal permeation enhancer, and has also found use in buccal drug delivery. It is a lipophilic surfactant in nature (Figure 10.4). Permeation of salicylic acid was enhanced by the pre-application of an Azone emulsion in vivo in a keratinized hamster cheek pouch model [35]. Octreotide and some hydrophobic compounds absorption have also been improved by the use of Azone [36], Azone was shown to interact with the lipid domains and alter the molecular moment on the surface of the bilayers [37], In skin it has been proposed that Azone was able to form ion pairs with anionic drugs to promote their permeation [38],... 

To deliver a therapeutically-effective dose transdermally using a TDD system with a reasonable size (e.g., < 20 cm ), the barrier properties of the skin for drug permeation must be overcome to effectively deliver the drugs transdermally at a controlled rate. The following approaches have been shown to potentially decrease the skin s barrier properties and enhance the transdermal permeation of the drugs (ji) ... 

Transdermal drug delivery (TDD) is known to offer many advantages over the oral and injectable routes for systemic drug delivery. However, the skin is a complex and dynamic organ with marked barrier function, which results in limitations and variations in the amount and nature of drugs that can be delivered across the skin and into the bloodstream. Thus a continual search for ways to optimize the permeation of drugs across the skin exists, in an attempt to enhance delivery and improve patient compliance. 

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