Development of Extended Release Oral Dosage Forms Prepared With Hot Melt Extrusion Method
Project no. 269 · Status: Kapanmış · 2017
Summary
In this study, floating systems produced with hot melt extrusion method were developed. Ketoconazole that is virtually insoluble in neutral or slightly acidic solutions and its dissolution and subsequent absorption are dependent on the presence of low gastric pH was choosen as model drug and so it was aimed to control its gastric residence time and plasma drug concentration. Firstly IR and UV spectrums were obtained to determine the physicochemical properties of ketoconazole. Solubility property of ketoconazole was determined in simulated gastric fluid. Formulations working with two different mechanisms to provide floating were developed using effervescent or non-effervescent excipients. Two different polymers such as Kollidon SR and Eudragit RS PO; three different floating agent such as sodium bicarbonate, calcium bicarbonate and ethanol; two different pore former polymers such as Klucel LF and Eudragit L100 to modify release profile were used to prepare floating systems. 24 different formulations were prepared and characterized using torque rheometry, in vitro buoyancy and in vitro release studies. In vitro release properties of formulations were analyzed spectrophotometrically and assay method was validated. As to the results of in vitro buoyancy study, it was seen that formulations F9, F19, F20, F22, F23 ve F24 can float in two seconds and maintain floating during 8 hours. Another result of the study is that the increase of amounts of polymers added to modify release characteristics of the formulations (Klucel LF ve Eudragit E100) increased the drug release rate. Formulation with the code of F20 with the formulation of %25(w/w) ketoconazole, %15(w/w) Eudragit E100 and %30(w/w) sodium bicarbonate and formulation with the code of F23 with the formulation of %25(w/w) ketoconazole, %15(w/w) Eudragit E100 and %30(w/w) ethanol were selected as optimum formulations. Drug content, thermal and morphological properties were investigated. Thermal properties were determined using DSC and TGA, morphological properties were determined using X-ray difractometry and SEM analyses. Consequently, it was thought that the optimum formulations are promising formulations to prepare gastric floating system with extended gastric residence time and to control the plasma drug concentration of ketoconazole.