Phenylethyl resorcinol smartLipids for skin brightening – Increased loading & chemical stability

• Published in: European journal of pharmaceutical sciences Vol. 137; p. 104992
• Main Authors: Köpke, Daniel, Müller, Rainer H., Pyo, Sung Min
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2019
• Subjects: Antioxidants - chemistry; Benzhydryl Compounds - chemistry; Chelating Agents - chemistry; Color; Discoloration prevention; Drug Carriers - chemistry; Drug Stability; Drug Storage; Improved chemical stability; Lipid nanoparticles; Lipids - chemistry; Nanoparticles - chemistry; Phenols - chemistry; Phenylethyl resorcinol; Radiation-Protective Agents - chemistry; Resorcinols - chemistry; Skin Lightening Preparations - chemistry; Skin whitening; smartLipids; Triazines - chemistry; Tyrosinase inhibition; Ultraviolet Rays; Tyrosinase inhibition; Discoloration prevention; Skin whitening; Phenylethyl resorcinol; Improved chemical stability; smartLipids; Lipid nanoparticles
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2019.104992

Phenylethyl resorcinol (PER, 4-(1-phenylethyl)1,3-benzenediol) is a very potent tyrosinase inhibitor with clinically proven effectiveness at already 0.5%. A major challenge of incorporating PER into dermal products is its high sensitivity against light. Previously, by incorporating PER in nanostructured lipid carriers (NLC), chemical stability and tyrosinase activity could be increased by 29% and 67%, respectively. Despite this, degradation still occurred accompanied with reddish discoloration of the formulation – not acceptable for market products. In this study PER was incorporated into smartLipids, the 3rd generation of lipid carriers. Compared to NLC, the smartLipids formulation had a higher PER loading, was PEG-free and used ECOCERT-certified Lanette N. For PER stabilization, 14 additives from three groups were investigated: UV blockers, antioxidants and chelating agents. The UV blockers Tinosorb S and Oxynex ST liquid, as well as the chelating agents ethylenediaminetetraacetic acid and phytic acid completely prevented reddish discoloration under test conditions (3 months in the dark and 7 days at light exposure). Investigating the stabilizing mechanisms, UV absorbers with high absorption in UV-A range were most effective (Tinosorb S, Oxynex liquid). They showed good stabilization in dark and at light exposure. Chelating agents had mainly an effect via pH shift to pH 2, thus are not suitable for dermal products requiring pH around 5. Antioxidants were less effective. The antioxidants propyl gallate and BHT showed best stabilization at storage in dark and slightly less at light exposure, not impairing the physical stability. Some antioxidants even accelerated discoloration (e.g. Tinogard TT). In general, low standard electrode potential (<0.4 mV) seems to be favorable for PER stabilization. In conclusion, Tinosorb S proved to be the best stabilizer; combination with an antioxidant is optional. By combination of smartPearls technology and the Tinosorb S stabilization, PER market products without discoloration are feasible. [Display omitted]