An overview of advanced formulation and nanotechnology-based approaches for solubility and bioavailability enhancement of silymarin

Approximately 70–80% of drugs in clinical drug development suffer low aqueous solubility, poor oral bioavailability, and limited intestinal permeability. Flavonoids are a group of phytochemicals that have been studied extensively due to their numerous health associated benefits. However, most of the flavonoids are categorized as compounds with low solubility-low permeability, which limits their clinical utility. Silymarin is a mixture of polyphenolic compounds that are extracted from milk thistle seeds. It possesses numerous beneficial pharmacological effects such as anti-cancer, anti-inflammatory, and anti-oxidant that are useful in a multitude of disorders. Although preclinical and clinical studies demonstrate the benefits of silymarin, its clinical utility is limited due to poor aqueous solubility, and low bioavailability. Formulation development is a widely employed approach to overcome these biopharmaceutical limitations. Multiple reviews have demonstrated silymarin's health associated benefits, however, there is still a lack of a comprehensive review focused on its chemistry, pharmacological effects, formulation, toxicity, patents, and clinical trials. The purpose of this study is to provide a review of various formulation development and nanotechnology-based approaches employed to increase the solubility, bioavailability, and therapeutic efficacy of silymarin. We have also reviewed data related to toxicity, patents, and clinical trials related to silymarin and its formulations.