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Application of Prodrug to Improve Skin Permeability: A Review

Mrunal Surve, Aniruddh Belubbi, Mushtaque Shaikh, Ojaskumar Agrawal


Administration of drug via skin has some limitations such as skin barrier, solubility of drug and partition coefficient etc. Stratum corneum which is an outer skin layer, acts as a barrier to the skin. Thus, prodrug has some applications to improve skin permeability. Prodrugs are defined as the compounds which are initially inactive but covert into their active form when reacted with several chemicals or enzymes at particular active site of body to show its desirable effect for a particular disease or condition. In skin permeability experiments, various vehicles can be used such as propylene glycol, short chain glycerides, dimethyl acetamide, cyclodextrins, N Methylpyrrolidone,azones, surfactants etc. Some mechanisms of prodrugs to improve skin permeation include, increase in partition coefficient of skin, enhanced solubilization of drug, decrease in crystal formation and modification in chemical structure of the drug. Apart from prodrug, the use of effective vehicle is of greater importance as well. As an example, for application of prodrug to improve skin permeation, two case studies have been discussed. Case study-1 includes the study of skin permeation using prodrug strategy for an opioid analgesic, Buprenorphine. In this study, the permeation of buprenorphine and its three alkyl esters across full thickness hairless mouse skin was evaluated. Thus, only acetyl buprenorphine appeared to be promising as a prodrug. In case study-2, antiviral drug acyclovir was esterified to obtain ester prodrugs of acyclovir. Hence, the five prodrugs of acyclovir showed similar skin permeability and amongst them, only acyclovir hexanoate showed 300- fold larger partition coefficient which depicts two times higher skin permeation than acyclovir. This review portrays the synthesis of prodrug to improve the skin permeability by applying enhancement mechanisms.


Prodrugs, enzymes, cyclodextrins, surfactants, analgesic

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