Formulation of silymarin nanoemulsions for dermal delivery

Abstract

Silymarin, a standardized extract from the seeds of Silybum marianum, has been used for liver diseases and recently it was reported to have many skin benefits including antioxidant, anti-tyrosinase, anti-inflammatory and antitumor. Delivery of silymarin through the skin has been an attractive as well as a challenging area for research. The present study aims to develop an optimal nanoemulsion containing silymarin using different surfactant mixture (smix) ratios and concentrations. Oil-in-water nanoemulsions were prepared by high-pressure homogenization method. Caprylic/capric triglycerides was used as an oil phase. Surfactant mixtures between Tween® 20 and Transcutol® were varied with different ratios and concentrations. Nanoemulsions were characterized for physical appearances, particle size and size distribution. Their physical stabilities were tested using centrifugation, heating-cooling cycle, and Ostwald ripening rate after storage at room temperature. The mean particle sizes of blank nanoemulsions were in the range of 88.3 to 227.2 nm with polydispersity index of 0.086 to 0.197. An increase in smix concentration resulted in smaller particle size. However, high Tween® 20, Transcutol®, or total smix concentration showed high Ostwald ripening rate and resulted in unstable nanoemulsions when stored in accelerated conditions. Nanoemulsion containing only Tween® 20 (F1 formulation) presented the lowest Ostwald ripening rate of 368.24 nm3/h and was selected. Carbopol® 940 (0.2 %w/w) was used as a gelling agent to improve the stability of nanoemulsion in heating-cooling cycles. 0.5 %w/w of silymarin was the maximum concentration that could be incorporated into nanoemulsion gel (SMNE gel). The particle size of SMNE gel was 112.7 nm with polydispersity index of 0.208. It showed good physical stability and passed six cycles of heating-cooling study. Consequently, silymarin content was 0.527 %w/w and gradually degraded during storage at 40 °C for three months. The entrapment efficiency of SMNE gel was 83.91 %. SMNE gel showed higher in vitro release of silymarin than silymarin microemulsion. The results supported our hypothesis that lower drug-system affinity in nanoemulsion which due to less surfactant should result in higher amount of silymarin released. For further studies, skin permeation of SMNE gel should be performed to compare with silymarin microemulsion, as well as skin irritation and its efficacy.