Stability-enhanced Hot-melt Extruded Amorphous Solid Dispersions via Combinations of Soluplus® and HPMCAS-HF

The aim of this study was to evaluate a novel combination of Soluplus (R) and hypromellose acetate succinate (HPMCAS-HF) polymers for solubility enhancement as well as enhanced physicochemical stability of the produced amorphous solid dispersions. This was accomplished by converting the poorly water-soluble crystalline form of carbamazepine into a more soluble amorphous form within the polymeric blends. Carbamazepine (CBZ), a Biopharmaceutics Classification System class II active pharmaceutical ingredient (API) with multiple polymorphs, was utilized as a model drug. Hot-melt extrusion (HME) processing was used to prepare solid dispersions utilizing blends of polymers. Drug loading showed a significant effect on the dissolution rate of CBZ in all of the tested ratios of Soluplus (R) and HPMCAS-HF. CBZ was completely miscible in the polymeric blends of Soluplus (R) and HPMCAS-HF up to 40% drug loading. The extrudates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and dissolution studies. DSC and XRD data confirmed the formation of amorphous solid dispersions of CBZ in the polymeric blends of Soluplus (R) and HPMCAS-HF. Drug loading and release of CBZ was increased with Soluplus (R) (when used as the primary matrix polymer) when formulations contained Soluplus (R) with 7-21% (w/w) HPMCAS-HF. In addition, this blend of polymers was found to be physically and chemically stable at 40 degrees C, 75% RH over 12 months without any dissolution rate changes.