Topical Delivery of 3-O-ethyl l-ascorbic Acid from Complex Solvent Systems

Fotis Iliopoulos,David J Moore,Majella E Lane,Bruno C Sil,A S M Monjur Al Hossain,Robert A Lucas

doi:10.3390/scipharm88020019

Abstract

3-O-ethyl l-ascorbic acid (EA), an ether derivative of Vitamin C, is widely used in skincare formulations. Previously, we reported the effects of neat solvents on EA percutaneous absorption and observed that 0.6–7.5% of the applied EA was delivered through the skin over 24 h. In this work, we designed complex formulations using combinations of solvents that may act synergistically and examined their impact on EA permeation in porcine skin in vitro under finite dose conditions. Binary combinations of propylene glycol (PG) with propylene glycol monolaurate (PGML) were effective in enhancing skin permeation of EA compared with individual solvents (p < 0.05). Combining PGML with 1,2-hexanediol (HEX) did not result in significantly higher EA permeation compared with the neat solvents (p > 0.05). Addition of the volatile solvent isopropyl alcohol (IPA) to PG solutions also did not improve EA skin delivery compared with neat PG. Ternary solvent systems containing PG:PGML were subsequently prepared by the addition of a lipophilic solvent, either isopropyl myristate (IPM), medium-chain triglycerides (MCT) or isostearyl isostearate (ISIS). The optimum vehicle, PG:PGML:IPM, promoted up to 70.9% skin delivery of EA. The PG:PGML:ISIS vehicles also promoted EA permeation across the skin, but to a significantly lesser extent than the IPM-containing vehicles. No enhancement of EA delivery was noted for the PG:PGML:MCT mixtures. These results will inform the development of targeted formulations for EA in the future.

Highlights

Vitamin C, known as l-ascorbic acid, is a widely used water-soluble antioxidant that has demonstrated various beneficial actions on human skin following topical application in vivo.These effects include significant reduction of clinical signs of photo-ageing in sun-exposed skin [1] as well as promotion of collagen synthesis in skin sites treated with a vitamin C-containing formulation [2].the molecule is unstable, readily undergoing oxidation in solutions and on exposure to air.This poses challenges for its use in topical formulations; the physicochemical properties of the compound are not optimal for skin delivery. 3-O-ethyl l-ascorbic acid (EA) is an ether derivative of vitamin C that is currently used in many personal care products [3,4]
Ternary solvent vehicles consisting of propylene glycol (PG):propylene glycol monolaurate (PGML):isopropyl myristate (IPM), PG:PGML:isostearyl isostearate (ISIS), and PG:PGML:medium-chain triglycerides (MCT)
EA solubility ranged from 64.4 ± 4.0 mg/mL to 550.4 ± 9.5 mg/mL, while for ternary solvent systems, EA solubility ranged from 104.6 ± 23.6 mg/mL to 340.9 ± 16.4 mg/mL (Figure 1)

Summary

Introduction

Vitamin C, known as l-ascorbic acid, is a widely used water-soluble antioxidant that has demonstrated various beneficial actions on human skin following topical application in vivo.These effects include significant reduction of clinical signs of photo-ageing in sun-exposed skin [1] as well as promotion of collagen synthesis in skin sites treated with a vitamin C-containing formulation [2].the molecule is unstable, readily undergoing oxidation in solutions and on exposure to air.This poses challenges for its use in topical formulations; the physicochemical properties of the compound are not optimal for skin delivery. 3-O-ethyl l-ascorbic acid (EA) is an ether derivative of vitamin C that is currently used in many personal care products [3,4]. Vitamin C, known as l-ascorbic acid, is a widely used water-soluble antioxidant that has demonstrated various beneficial actions on human skin following topical application in vivo. These effects include significant reduction of clinical signs of photo-ageing in sun-exposed skin [1] as well as promotion of collagen synthesis in skin sites treated with a vitamin C-containing formulation [2]. The molecule is unstable, readily undergoing oxidation in solutions and on exposure to air This poses challenges for its use in topical formulations; the physicochemical properties of the compound are not optimal for skin delivery. EA has been found to have good stability in several commonly used solvents, with a reported recovery of greater than 90% after 120 h at 32 ± 1 ◦ C [5]

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