FORMULATION AND EVALUATION OF LIQUISOLID COMPACTS OF DABIGATRAN ETEXILATE MESYLATE

The term liquisolid systems (LS) is a powdered form of liquid drug formulated by converting liquid or solid lipophilic drug in suitable non-volatile solvent systems into dry looking, non-adherent, free-flowing, and readily compressible powdered mixtures by blending with selected carrier and coating materials. The aim of the present study is to improve the solubility of poorly water soluble drug, dabigatran etexilate mesylate a BCS class II drug. Dabigatran Etexilate Mesylate is an inactive pro-drug that is converted to dabigatran, the active form used as an anti-coagulant. Various non-volatile solvents (PEG 600, PEG 400, Castor oil, Span 80, Tween 80, Glycerine, Transcutol, Olive oil, Liquid Paraffin) were used and maximum solubility was observed in combination of span80 and castor oil (400.96ug/ml). Selection of carrier materials like Maize starch, MCC, Avicel pH 101 and 102 and Prosolv SMCC 50 with a loading factor of 0.72, 0.75, 0.77, 0.87 and 1.75 respectively were optimized. To this admixture, coating material Aerosil 200 in different ratios (R=5, 10, 15, 20, 25) was added to enhance the flow property. Finally the powdered material is compressed to tablets by direct compression using 11.9mm. The tablets were evaluated for physicochemical properties, and dissolution studies. Among all formulations, dabigatran etexilate mesylate liquisolid compacts containing Prosolv SMCC 50 (LSP) showed higher dissolution rate (99.8% in 30 min) than the pure drug (11.15% in 45 min). FTIR studies and DSC studies revealed that there is no significant interaction between the drug and excipients. The XRD analysis confirmed formation of a solid solution inside the compact matrix. Formulations were stable. From this study it can be concluded that the liquisolid technique is a promising alternative for improvement of dissolution property of waterinsoluble drugs. Hence Span80+Castor oil (non-volatile solvent) and Prosolv SMCC 50 were optimized in enhancing the dissolution rate of dabigatran etexilate mesylate.