Characterisation of Preformulation Parameters to Design, Develop and Formulate Silymarin loaded PLGA Nanoparticles for Liver Targeted Drug Delivery

Abstract

Silymarin, a flavonolignan,derived from Silybum marianum, family Asteraceae has long been used as a hepatoprotective remedy. Silymarin has cytoprotective activities due to its antioxidant property and free radical scavenging activity. It inhibits the binding of hepatotoxins to receptor sites, protects hepatocyte membranes, enhances liver parenchyma regeneration and increases glutathione levels. The pharmacokinetic studies of past three decades revealed that Silymarin has poor absorption, rapid metabolism especially by Phase II metabolism and ultimately poor oral bioavailability. Typical oral adult dose of Silymarin is 240-800mg /day .It is a non-lipophilic and poorly water soluble compound with water solubility of 0.04mg/ml. Only 20-30% of oral Silymarin is absorbed from gastrointestinal tract where it undergoes extensive entero-hepatic circulation. The advanced type of formulation like polymeric nanoparticles (PNPs) can be successfully utilised for bioavailability enhancement and targeting the Silymarin to hepatocytes. A controlled release PNP of Silymarin was prepared by solvent evaporation method using Poly Lactic-co-Glycolic Acid (PLGA) as biodegradable polymer. Prior to the development of this novel dosage form, it is very important to identify fundamental physical and chemical properties of the drug molecule and other divided properties of the drug powder. This data helps in many of the subsequent events and approaches towards the development of a better formulation. Preformulation studies included determination of solubility, moisture content, partition coefficient, melting point , powder properties like tapped density, bulk density, compressibility index, flow properties like angle of repose, excipient compatibility, entrapment efficiency, release profile of nanoparticles like dissolution, stability studies like effect of temperature and humidity and analysis by scanning Electron Microscopy.