• Dissolution and Solubility Enhancement of the Poorly Water Soluble Drug by Forming Solid Dispersion with a Novel Polymeric Solubilizer (Soluplus®)

      Lim, Hanpin; Hoag, Stephen W. (2012)
      The aim of this study was to investigate the potential of a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol grafted copolymer (Soluplus®) to enhance the dissolution and solubility of carbamezapine by forming solid dispersion using solvent casting and hot-melt extrusion techniques. The second aim of this study was to characterize the effects of four different plasticizers (polyethylene glycol 6, triethyl citrate, propylene glycol and glycerin) on the physical-mechanical properties of the solid dispersion formed by solvent casting technique. The third aim was to investigate the ability of near infrared spectroscopy (NIRS) to qualitatively predict the solid state form of carbamazepine within a solid dispersion. The Carbamazepine-Soluplus solid dispersions were prepared by solvent casting and hot-melt extrusion. The thermal properties and polymorphic form of the neat carbamazepine, Soluplus® and the solid dispersions were studied using modulated differential scanning calorimetry, powder X-ray diffraction and near-infrared spectroscopy. The dissolution and solubility of the physical mixtures and solid dispersions were analyzed. The mechanical properties of the films were determined using an Instron® 8521 System. The equilibrium solubility of the physical mixtures and solid dispersions of Carbamazepine- Soluplus® were increased. The extent of increase was influence by the drug: polymer ratio with higher polymer content resulting in higher solubility. Higher drug dissolution rate was seen in all solid dispersions formed with higher drug dissolution with increasing Soluplus® proportion. The four plasticizers deceased the Tg, tensile strength and Young's modulus and increased in the percent elongation and toughness of the films. In terms of mechanical properties, the plasticizer PEG-6 was the most efficient plasticizer creating the greatest change in mechanical properties for a given concentration. This study also showed that the analysis of NIR spectra in 1468 nm wavelength region was able to qualitatively distinguish between the amorphous and polymorphic form III of carbamazepine. This finding is important as it suggests NIR can be used to detect the stability of the carbamazepine-soluplus® solid dispersion system (i.e. precipitation from the metastable amorphous form to the most stable polymorphic form III).