(681f) Applications of Affinisol HPMC in Hot Melt Extrusion

The objective of this study was to assess the ability of AFFINISOL™ HPMC to be processed by hot melt extrusion and to determine the influence of molecular weight grade on dissolution rate and supersaturation maintenance. AFFINISOL™ HPMC and griseofulvin were pre-blended in a Turbula mixer for 10 minutes and extruded via a Leistritz Nano16 hot melt extruder utilizing a 2 mm strand die. Resulting strands were either milled in a Fitz mill at 9000 rpm or pelletized via a ConAir pelletizer. Milled extrudates were physically characterized by Differential Scanning Calorimetry (DSC), Thermogravimetric analysis, and powder X-Ray Diffraction (XRD). Dissolution was performed in pH 5.8 phosphate buffer for 24 hours in a USP II dissolution apparatus with a paddle speed of 50 RPM. Dissolved drug was quantified by HPLC. Thermogravimetric analysis revealed no early onset of degradation at the temperatures used during extrusion. All formulations were successfully extruded below the melting point of the API into 2 mm strands which were translucent in nature with minimal color change observed. All extrudates were amorphous as evidenced by the absence of any crystalline peaks in the XRD diffraction patterns or melting endotherms in DSC thermograms. All molecular weight grades achieved and maintained supersaturation over the 24 hour testing period. Dissolution rate was dependent upon molecular weight grade utilized with higher molecular weights resulting in slower dissolution.  AFFINISOL™ HPMC can be successfully processed by hot melt extrusion and is capable of generating amorphous solid solutions. Release rate of the API can be controlled by varying the molecular weight. By using hot melt extrusion and selecting the appropriate molecular weight it is possible to get both controlled release and supersaturation concurrently.

Copyright American Association of Pharmaceutical Scientists 2013