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

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.

Film‐ and ointment‐based delivery systems for the transdermal delivery of TNP‐470

“…Additionally, the water‐repellent properties of hydrocarbon ointment supposed to prevent hydrolysis of TNP‐470 and insure its stability. In order to enhance the drug penetration to the skin, we added isopropyl myristate, a skin penetration enhancer, compound which reversibly lower the protective barrier of stratum corneum, the outermost layer of the skin …”

“…White wax (Sigma‐Aldrich, 18635 ) is the purified wax obtained from the honeycomb of the bee Apis mellifera . In order to enhance the drug penetration to the skin, we added to the ointment formulation isopropyl myristate (Merck, 8.17066), a skin penetration enhancer . For the drug incorporation procedure, a small quantity (up to 20 mg) of the TNP‐470 powder is mixed with an equal portion of the base until the product is uniform.…”

“…In order to enhance the drug penetration to the skin, we added isopropyl myristate, a skin penetration enhancer, compound which reversibly lower the protective barrier of stratum corneum, the outermost layer of the skin. 16,25 Surprisingly, the permeated amount through the pig skin from hydrocarbon ointment, containing penetration enhancer, was lower than the chitosan-TNP-470 enhancer free film-4% compared with 6% after 48 hours and 4.5% compared with 9% after 120 hours. Possible explanation for this phenomenon could be the high loading of TNP-470 in chitosan film (50%) compared with only 10% in ointment, which enhance the diffusion of the drug through the skin due to a bigger gradient.…”

“…24 In order to enhance the drug penetration to the skin, we added to the ointment formulation isopropyl myristate (Merck, 8.17066), a skin penetration enhancer. 25 For the drug incorporation procedure, a small quantity (up to 20 mg) of the TNP-470 powder is mixed with an equal portion of the base until the product is uniform. Geometric dilution is continued until all portions of the powder and base are combined and homogenously mixed.…”

Preparation, Characterization, and In Vivo Pharmacokinetic Evaluation of Polyvinyl Alcohol and Polyvinyl Pyrrolidone Blended Hydrogels for Transdermal Delivery of Donepezil HCl

“…PG has the potential to intercalate into the polar head groups of the lipid bilayer due to its hydrophilic nature and significantly enhances the mean interfacial area per lipid [48]. Moreover, skin partitioning and the barrier function of the skin are decreased by enhanced trans-epidermal water loss and kallikrein 7 (KLK 7) protease activity, which might account for the enhancement of skin permeation [49,50]. Yamane et al reported that the flux and permeability coefficient of 5-fluorouracil was increased with the addition of terpenes to the PG system.…”