Chemical Permeation Enhancers for Topically-Applied Vitamin C and Its Derivatives: A Systematic Review

This paper reports the permeation-enhancing properties and safety of different chemical permeation enhancers (CPEs) on the topical delivery of vitamin C (VC) and its derivatives. A literature search using search keywords or phrases was done in PubMed (R), ScienceDirect, and MEDLINE databases. The calculated Log P (cLog P) values were referenced from PubChem and the dermal LD50 values were referenced from safety data sheets. Thirteen studies described the permeation-enhancing activity of 18 identified CPEs in the topical delivery of VC. Correlation analysis between ER and cLog P values for porcine (r = 0.114) and rabbit (r = 0.471) showed weak and moderate positive correlation, while mouse (r = -0.135), and reconstructed human epidermis (r = -0.438) had a negative correlation. The majority (n = 17) of the CPEs belonged to Category 5 of the Globally Harmonized System of Classification or low toxicity hazard. CPEs alone or in combination enhanced permeation (ER = 0.198-106.57) of VC in topical formulations. The combination of isopropyl myristate, sorbitan monolaurate, and polyoxyethylene 80 as CPEs for VC resulted in the highest permeation enhancement ratio.