DISSOLUTION ENHANCEMENT OF POORLY WATER SOLUBLE EPROSARTAN BY HOT MELT EXTRUSION TECHNIQUEAbstract
Objective: The prodigious challenge in the pharmaceutical industries was to enhance the solubility and the permeability of those drugs as key factors to improve their bioavailability. Various techniques have been used to improve the drug water solubility and release profile, and solid dispersions are considered to be the most successful techniques. The aim of the present study was to improve the solubility and bioavailability of a poorly water-soluble antihypertensive drug (Eprosartan) in the human body, using a solid dispersion technique (hot melt extrusion) and comparison with other methods. Methods: The development of solid dispersions as a practically viable method to enhance the bioavailability of poorly water-soluble drugs to overcome the limitations of previous approaches such as salt formation, solubilization by co-solvents and particle size reduction studies revealed that drugs in solid dispersion need not necessarily exist in the micronized state. Solid solution was prepared by solvent evaporation, fusion method, hot melt extrusion technique at 1:1.1, 1:2 (Eprosartan: Soluplus) and 1:1.5:0.5 (Eprosartan:Soluplus: Kollidan/Plasdone) ratios respectively. Solid Solution was evaluated for saturation solubility, dissolution rate, XRD, FTIR, and DSC. Results: From the studies, it was concluded that the solubility of Eprosartan was increased by the solid dispersion approach. Among the three techniques, the solubility of the drug increased by hot melt extrusion technique when compared to solvent evaporation and fusion methods. Therefore, the carrier surplus was suitable for enhancement of solubility of Eprosartan than other carriers used in this investigation such as kollidon VA64 and plasdone K29/32 and DSC, XRD data concluded that hot melt extrusion process devastates the edge peaks of Eprosartan which indicate the complete conversion of the crystal form of Eprosartan to amorphous form. Dissolution and solubility studies also showed enhancement in the release rate of hot melt extrusion complex. Stability studies at 40 º C / 75% RH were studied, and it shows that the sample is stable even after 90 days of study. Hot melt extrusion is commensurate method to improve dissolution and permeability of poorly water-soluble Eprosartan. Conclusion: In the present study, an attempt was made to formulate and evaluate the Eprosartan solid dispersions using soluplus, kollidon VA64 and plasdone K29/32 as carriers, prepared by using solvent evaporation, fusion, and hot melt extrusion methods. From the studies, it was concluded that the solubility of Eprosartan was increased by the solid dispersion approach. Among the three techniques, the solubility of the drug increased by hot melt extrusion technique when compared to solvent evaporation and fusion methods. Therefore, the carrier soluplus was suitable for enhancement of solubility of Eprosartan than other carriers used in this investigation, such as kollidon VA64 and plasdone K29/32. The low hygroscopicity and low glass transition temperature of soluplus make it particularly suitable for hot melt extrusion.