Theoretical and practical evaluation of lowly hydrolyzed polyvinyl alcohol as a potential carrier for hot-melt extrusion.

Polyvinyl alcohol (PVA) is considered to be an unsuitable carrier for hot-melt extrusion (HME) due to its low processability. In this study, we focused on a lowly hydrolyzed PVA (JR-05, 70.0-74.0% hydrolyzed, L-PVA) to evaluate the potential use of L-PVA as a carrier for HME using the Hoftyzer and Krevelen method and thermodynamic models. These evaluations for drug-polymer systems based on the Flory-Huggins theory predicted the physicochemical properties of the solubility and miscibility between indomethacin (IND) and PVAs. Prior to initiating formulation studies, construction of IND and PVA phase diagrams provided guidance for design process conditions in HME. On the basis of the results of the validation studies, a conventional grade of PVA (JP-05, 87.0-89.0% hydrolyzed) is unlikely to be suitable as a carrier of HME due to its low plasticity, resulting in rapid recrystallization in the evaluation of in vitro dissolution and stability caused by poor miscibility. On the other hand, JR-05 demonstrated high processability, leading to the preparation of miscible extrudate with a high stability and an excellent in vitro dissolution profile due to its unique micelle-forming capability. These findings suggest that L-PVA brings about new carrier options among non-ionic polymers for HME.