Formulation and Evaluation of Sustained Release Extrudes Prepared via Novel Hot Melt Extrusion Technique

The purpose of the present investigation is to emphasize the application of hot-melt extrusion technique (HMET) for the preparation of sustained release matrix formulation of highly dosed, freely soluble drugs. In this study, sustained release multiple unit dosage of venlafaxine hydrochloride (VH) was prepared by HMET. Custom design was used to screen the effect of four factors-type of polymer (ethylcellulose and eudragit RSPO) (X (1)), amount of polymer (X (2)), type of plasticizer (DBS, ATBC, TEC, and PEG) (X (3)), and plasticizer concentration (X (4)), on the drug release at 8 h (Y1) and machine torque (Y2). The experiments were carried out according to a four-factor 16-run statistical model and subjected to 12-h dissolution study in purified water. The significance of the model was indicated by ANOVA. Results of in vitro release study indicate that formulations prepared with higher amount of ethylcellulose and DBC show significant retardation at 8 h. The result shows that increase in concentration of polymer with the combination of water insoluble plasticizer (DBS and ATBC) has better sustained release while increasing concentration of TEC and PEG results faster in vitro release. Besides that increase in plasticizer concentration helps in reducing the melt temperature and machine torque. The in vivo study was performed, and formulations were compared using area under the plasma concentration-time curve (AUC(0-a)), time to reach peak plasma concentration (T-max), and peak plasma concentration (C-max). The drug release profiles of extrudes were found to fit both diffusion and surface erosion models. Further to this, scanning electron microscopy, differential scanning calorimetry, and X-ray diffraction analysis of the hot-melt extrudates demonstrated that VH remained crystalline and was homogeneously dispersed throughout the polymer matrix.