Abstract
The drug delivery within the stratum corneum of the skin prevails a challenging area for the pharmaceutical field, especially to the formulation scientists. Several investigations revealed that the lipid domain, which is the integral component of the transport barrier, must be breached if it is to be delivered transdermally at an appropriate rate. In particular, transdermal drug delivery has intrigued researchers with multiple suggestions because multiple dosing or insufficient drug delivery or characteristics of various drugs often results in low therapeutic effects. The application of permeation or penetration enhancers may prolong the number of drugs that can be offered topically. The application of any natural permeation enhancer is innoxious over the artificial permeation enhancers. The natural permeation enhancers are investigated, so notably include essential oils, terpenes, terpenoids, fatty acid esters, etc., have a certain effect in the transdermal drug delivery system. Despite decades of investigation on the natural chemical penetration enhancer, the researchers could not establish the effectiveness of natural penetration enhancers clinically due to the lack of in vivo models. Several factors, like solubility, solvent selection, experimental models, etc., has restricted the application and development of natural penetration enhancers in topical drug delivery systems, especially in the patches. Therefore, further investigation needs to do on skin irritation to decide natural penetration enhancers controlling optimum enhancement effects with minimal skin irritation. This review gives a comprehensive literature survey on naturally obtained chemical penetration enhancers and their future possibilities.
 Keywords: Topical Drug delivery system, Natural products, Penetration enhancer, Stratum corneum, In vivo models.
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