Solubility Enhancement and Antioxidant Potential of Silymarin: A Poorly Water-soluble Drug

Abstract

Background: Silymarin is extracted from the seeds of milk thistle (Silybum marianum), exhibits antioxidant properties, and is considered to treat numerous hepatic ailments like chronic liver disease, cirrhosis, and chemical degradation of liver cells and prevent hepatotoxicity from various drugs. Objective: The objective of the present study was to preclude the problem of poor dissolution of the relatively water-insoluble drug by formulating solid dispersions of the drug. Methods: Solid dispersions of silymarin were prepared by solvent evaporation method by using different polymers, i.e., PEG 6000 and poloxamer 407, in various ratios such as 1:2, 1:4 and 1:6. The compatibility of ingredients with the drug was tested by using Differential scanning calorimetry (DSC), X-Ray Diffractometry, and Fourier Transform-Infrared Spectroscopy (FT-IR). The scavenging activity of DPPH (2,2 diphenyl-1-picrylhydrazyl) radical was used to study the antioxidant activity, and an in vitro release study was conducted using phosphate buffer pH 6.8 as dissolution medium followed by the kinetic assessment to study the drug release mechanism. Results: Solid dispersions with different polymers were successfully prepared by the solvent evaporation method. FTIR spectroscopy and DSC showed no chemical interaction between the drug and polymers. Powder XRD analyses of optimized solid dispersions showed a relative decrease in crystallinity compared to the pure drug. The dissolution profile of solid dispersions successfully exhibited 90.78% drug released, and the optimized batch was found to follow Higuchi drug release kinetics with an R2 value of 0.990. Furthermore, the optimized formulation F6 showed higher antioxidant activity compared to pure silymarin and ascorbic acid. Conclusion: The elevated bioavailability, as well as absorption, consistently regulates the specific therapeutic effect of the water-insoluble drug. The specific response of silymarin to various bodily functions upgrades various activities like anti-aging effects, anti-cancer, antihypertensive, etc. Solid dispersion of drugs with good aqueous solubility results in a decrease in dose frequency and enhanced specificity of the drug mechanism.