Enhancers

Stratum corneum is the outer most layer of the skin and its main function is to prevent entry of exogenous substances into the systemic circulation via the skin. Stratum corneum contains keratinized remnants of epidermal cells, which makes it difficult for exogenous substances to traverse it.1

Designing products which can pass through the stratum corneum and reach the target site without impacting the skin membrane is a challenging task. A simple option to overcome this challenge is the use of absorption enhancer or penetration enhancers.1

Penetration enhancers are the agents that penetrate into the skin and interact with skin constituents to promote drug/product flux or reversibly decrease the barrier resistance. The purpose of the enhancers is to make the drug/product more easily soluble on the stratum corneum and thus make them diffuse into the skin surface.2

In herlip® gel, lecithin nano lipids from soya beans and menthol from mint leaves act as absorption or penetration enhancers.

Menthol as an absorption enhancer

Apart from its use as a cooling and counterirritant, menthol is also used as a penetration enhancer in pharmaceutical formulation and cosmetics due to its high efficiency and relative safety.3

Terpenes and terpenoids, present in menthol are responsible for its skin penetration enhancer effects. Menthol impairs the lipid packing of stratum corneum and promotes permeation of chemical substances into the stratum corneum. The penetration enhancement mechanism of menthol is characterized mainly by the disruption of the highly ordered stratum corneum lipid in low concentrations and an improvement in the partitioning of drugs into the stratum corneum in high concentrations.3

Wan et al. found that a rise in temperature and concentration within a specific range (1-20%) improved the penetration-enhancing property of menthol and the floppiness of lipid bilayer.4

Lecithin nano lipids from soya beans

Lecithin is a natural surfactant isolated from eggs or soya bean. Lecithin is a mixture of phospholipids with phosphatidylcholine as a main component (up to 98% w/w). Soybean-lecithin enhances the penetration of a drug through the skin.5,6

Lecithin has a wide variety of roles in food industries, pharmaceuticals, and cosmetics. Lecithin is used as a viscosity modifier, solubilizer, emulsifier, stabilizer, and penetration enhancer.6

Nanoparticles are one of the main options for the delivery of poorly aqueous bioactive compounds.  Encapsulation of natural compunds in nanoparticles might generate stable deliverable forms, which improves the availability and solubility of the bioactive compounds.7

Lecithin has been used as a phospholipid-structured system for topical drug delivery, or in the preparation of various nanosystem delivery vehicles, such as micelle, liposomes, microemulsions and nanoparticles. Lecithin in the nanosystem generates a three-dimensional network that immobilizes the contiguous. Lecithin is a safe and biocompatible excipient. 7

References
  1. Shaikh I.M., Jadhav K.R., Kadam V.J. (2015) Lecithin Organogels in Enhancing Skin Delivery of Drugs. In: Dragicevic N., Maibach H. (eds) Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45013-0_21
  2. IB Pathan, CM Setty. Chemical Penetration Enhancers for Transdermal Drug Delivery Systems. 2009. Tropical Journal of Pharmaceutical research. Available at:  https://www.tjpr.org/admin/12389900798187/2009_8_2_11.pdf. Accessed on: 08 February 2021.
  3. Yang S, Wang R, Wan G, et al. A Multiscale Study on the Penetration Enhancement Mechanism of Menthol to Osthole. J Chem Inf Model. 2016;56(11):2234-2242.
  4. Wang H, Meng F. The permeability enhancing mechanism of menthol on skin lipids: a molecular dynamics simulation study. J Mol Model. 2017;23(10):279.
  5. Pérez SE, Gándola Y, Carlucci AM, González L, Turyn D, Bregni C. Formulation Strategies, Characterization, and In Vitro Evaluation of Lecithin-Based Nanoparticles for siRNA Delivery. J Drug Deliv. 2012;2012:986265.
  6. J. Varshosaz, S. Andalib, M. Tabbakhian, et al. Development of Lecithin Nanoemulsion Based Organogels for Permeation Enhancement of Metoprolol through Rat Skin. Journal of Nanomaterials, vol. 2013, Article ID 139437, 10 pages, 2013.
  7. Perez-Ruiz AG, Ganemb A, Olivares-Corichi IM, et al. Lecithin–chitosan–TPGS nanoparticles as nanocarriers of (−)-epicatechin enhanced its anticancer activity in breast cancer cells. RSC Adv., 2018, 8, 34773-34782.
  8.