SOLUBILITY ENHANCEMENT OF A POORLY SOLUBLE HEPATOPROTECTIVE DRUG SILYMARIN USING COCRYSTALLIZATION TECHNIQUE

Silymarin, a flavonolignan complex obtained from Silybum marianum, is widely used for its hepatoprotective antioxidant & anti-inflammatory activities. However, its clinical application is limited due to poor aqueous solubility and low oral bioavailability, as it belongs to the Biopharmaceutics Classification System of class II drug category. The present study aims to enhance the solubility characteristics of silymarin through the pharmaceutical cocrystallization technique. Cocrystals of silymarin were prepared by the antisolvent precipitation technique using coformers generally recognised as safe. The FTIR result establishes the compatibility of the drug silymarin with selected coformers in this study. The prepared cocrystals were evaluated using techniques like saturated solubility, melting point, microscopy and XRD. The saturated solubility of silymarin cocrystals increases many-fold in compared to the pure drug. The decrease in melting point of cocrystals and peak shifts in XRD towards higher 2θ values with reduced d-spacing of more crystalline percentages proved the formation of new crystalline phases. Microscopic image of pure silymarin drug compared with different cocrystals prepared, showing significant differences. Among all formulations, the silymarin–ascorbic acid cocrystal exhibited the highest solubility, improved particle morphology, and favourable crystalline characteristics. These results of this study confirm that the cocrystallization is an effective and promising approach to enhance the solubility and oral bioavailability of poorly water-soluble drugs like silymarin.