Formulation and Evaluation of Silymarin as Microcrystals by In- Situ Micronization Technique

Abstract

Silymarin (SM) is a plant extract obtained from Silybum marianum( milk thistle). It is hepatoprotective drug class II type according to Biopharmaceutics Classification System. It is practically insoluble with low bioavailability.Micro/nanonization during crystallization, surface modification and crystal structure modification may improve the solubility and dissolution rate of poorly water-soluble drugs.The aim of this study was to enhance the water solubility and dissolution rate of SM by in-situ micronization using solvent change either by stirring or ultrasonic method. Polymers like gelatin, PVP-K30, HPMC15, pulullan were used to stabilize the prepared ultra-fine crystals. Effect of type and concentration of hydrophilic polymer, solvent: anti-solvent volume ratio and the effect of ultrasonic irradiation were studied. The prepared microcrystals were evaluated for their percent yield, water solubility, crystals structure by XRD, DSC, and SEM. Particle size and dissolution rate were also determined. Silymarin microcrystals prepared by ultrasonic method and stabilized by 0.1% w/v gelatin using 1:2 solvent: anti-solvent volume ratio showed the best results with percent yield 93.4±2.7% and particle size reduction from mean diameter of 1.5µm (untreated SM) to 0.43µm with uniform morphology and enhanced solubility for about four folds with improvement in dissolution.