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      Chemical Enhancer: A Simplistic Way to Modulate Barrier Function of the Stratum Corneum

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          Abstract

          Human skin could be a prime target to deliver drugs into the human body as it is the largest organ of human body. However, the main challenge of delivering drug into the skin is the stratum corneum (SC), the outer layer of epidermis, which performs the main barrier function of the skin. Scientists have developed several techniques to overcome the barrier properties of the skin, which include other physical and chemical techniques. The most common and convenient technique is to use special formulation additives (chemical enhancers, CEs) which either drags the drug molecule along with it or make changes in the SC structure, thereby allowing the drug molecule to penetrate in to the SC. The main focus is to deliver drugs in the certain layers of the skin (for topical delivery) or ensuring proper percutaneous absorption (for transdermal delivery). However, skin drug delivery is still very challenging as different CEs act in different ways on the skin and they have different types of interaction with different drugs. Therefore, proper understanding on the mechanism of action of CE is mandatory. In this article, the effect of several CEs on skin has been reviewed based on the published articles. The main aim is to compile the recent knowledge on skin-CE interaction in order to design a topical and transdermal formulation efficiently. A properly designed formulation would help the drug either to deposit into the target layer or to cross the barrier membrane to reach the systemic circulation.

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          Most cited references73

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          Penetration enhancers.

          One long-standing approach for improving transdermal drug delivery uses penetration enhancers (also called sorption promoters or accelerants) which penetrate into skin to reversibly decrease the barrier resistance. Numerous compounds have been evaluated for penetration enhancing activity, including sulphoxides (such as dimethylsulphoxide, DMSO), Azones (e.g. laurocapram), pyrrolidones (for example 2-pyrrolidone, 2P), alcohols and alkanols (ethanol, or decanol), glycols (for example propylene glycol, PG, a common excipient in topically applied dosage forms), surfactants (also common in dosage forms) and terpenes. Many potential sites and modes of action have been identified for skin penetration enhancers; the intercellular lipid matrix in which the accelerants may disrupt the packing motif, the intracellular keratin domains or through increasing drug partitioning into the tissue by acting as a solvent for the permeant within the membrane. Further potential mechanisms of action, for example with the enhancers acting on desmosomal connections between corneocytes or altering metabolic activity within the skin, or exerting an influence on the thermodynamic activity/solubility of the drug in its vehicle are also feasible, and are also considered in this review.
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            Predicting skin permeability.

            Published permeability coefficient (Kp) data for the transport of a large group of compounds through mammalian epidermis were analyzed by a simple model based upon permeant size [molecular volume (MV) or molecular weight (MW)] and octanol/water partition coefficient (Koct). The analysis presented is a facile means to predict the percutaneous flux of pharmacological and toxic compounds solely on the basis of their physiocochemical properties. Furthermore, the derived parameters of the model have assignable biophysical significance, and they provide insight into the mechanism of molecular transport through the stratum corneum (SC). For the very diverse group of chemicals considered, the results demonstrate that SC intercellular lipid properties alone are sufficient to account for the dependence of Kp upon MV (or MW) and Koct. It is found that the existence of an "aqueous-polar (pore) pathway" across the SC is not necessary to explain the Kp values of small, polar nonelectrolytes. Rather, their small size, and consequently high diffusivity, accounts for their apparently larger-than-expected Kp. Finally, despite the size and breadth of the data set (more than 90 compounds with MW ranging from 18 to greater than 750, and log Koct ranging from -3 to +6), the postulated upper limiting value of Kp for permeants of very high lipophilicity cannot be determined. However, the analysis is able to define the physicochemical characteristics of molecules which should exhibit these maximal Kp values.(ABSTRACT TRUNCATED AT 250 WORDS)
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              Skin penetration enhancers.

              The skin has evolved to prevent excessive water loss from the internal organs and to limit the ability of xenobiotics and hazardous substances to enter the body. Notwithstanding this barrier function, a number of strategies have been developed by scientists to deliver drugs to and through the skin. The aim of this review is to consider the various types of chemical penetration enhancers (CPEs) which have been investigated in the scientific literature. Potential pathways for CPEs to exert their action are examined with reference to the physical chemistry of passive skin transport. The emphasis is on those studies which have focussed on human and porcine skin because of the limitations associated with skin permeation data collated from other species. Where known, the mechanisms of action of these compounds are also discussed. Examples of enhancers used in commercial topical and transdermal formulations are provided. It is proposed that overall the effects of CPEs on the skin barrier may best be explained by a Diffusion-Partition-Solubility theory. Finally, some of the limitations of studies in the literature are considered and the importance of monitoring the fate of the penetration enhancer as well as the active is highlighted. Copyright © 2013 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Adv Pharm Bull
                Adv Pharm Bull
                Adv Pharm Bull
                APB
                TBZMED
                Advanced Pharmaceutical Bulletin
                Tabriz University of Medical Sciences
                2228-5881
                2251-7308
                June 2018
                19 June 2018
                : 8
                : 2
                : 169-179
                Affiliations
                1Department of Pharmacy, East West University, A/2, Jahurul Islam City Gate, Aftab Nagar Main Rd, Dhaka-1212, Bangladesh.
                2Department of Pharmacy, BRAC University, 66 Bir Uttam AK Khandakar Road, Dhaka 1212, Bangladesh.
                Author notes
                [* ] Corresponding author: Md Mesbah Uddin Talukder, Tel: +88 01746637487, mesbah.talukder@ 123456bracu.ac.bd
                Article
                10.15171/apb.2018.021
                6046426
                30023318
                cd2fcecb-d7ce-4ec4-adbe-a23548840345
                ©2018 The Authors.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or the publishers.

                History
                : 19 February 2018
                : 26 May 2018
                : 29 May 2018
                Page count
                Figures: 3, Tables: 1, References: 85, Pages: 11
                Categories
                Review Article

                barrier function,chemical enhancer,drug delivery,modification of skin,stratum corneum

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