Application of Film-Casting Technique to Investigate Drug-Polymer Miscibility in Solid Dispersion and Hot-Melt Extrudate.

Determination of drug-polymer miscibility is critical for successful development of solid dispersions. This report details a practical method to predict miscibility and physical stability of drug with various polymers in solid dispersion and, especially, in melt extrudates by applying a film-casting technique. Mixtures of itraconazole (ITZ) with hydroxypropylmethylcellulose phthalate (HPMCP), Kollidon® VA 64, Eudragit® E PO, and Soluplus® were film-casted, exposed to 40°C/75% RH for 1 month and then analyzed using differential scanning calorimetry (DSC), powder X-ray diffractometry, and polarized light microscopy (PLM). ITZ had the highest miscibility with HPMCP, being miscible at drug to polymer ratio of 6:4 (w/w). There was a downward trend of lower miscibility with Soluplus® (miscible at 3:7, w/w, and a few microcrystals present at 4:6, w/w), Kollidon® VA 64 (2:8, w/w) and Eudragit® E PO (<1:9, w/w). PLM was found more sensitive to detect drug crystallization than DSC and powder X-ray diffractometry. There was general correlation between results of film casting and hot-melt extrusion (HME) using a twin screw extruder. For ITZ-Soluplus® mixtures, HME at 4:6 (w/w) resulted in a single phase, whereas drug crystallization was observed at higher drug load. HME of ITZ-Kollidon® VA 64 mixtures also correlated well with the miscibility predicted by film casting.