Assessment of critical material attributes of polyethylene oxide for formulation of prolonged-release tablets

Abstract

Physicochemical evaluation of polyethylene oxide (PEO) polymers with various molecular weights was performed at molecular (polymeric dispersion) and bulk level (powders, polymeric films, and tablets) with the aim of specifying polymer critical material attributes with the main contribution to drug release from prolonged-release tablets (PRTs). For this purpose, grades of PEO with low, medium, and high viscosity were used for formulating PRTs with a good soluble drug substance (dose solubility volume 15 ml). The results revealed a good correlation (r2=0.88) between in vivo data (pharmacokinetic parameters: Cmax and AUC) and the elastic property of PEO films determined with the nanoindentation method, demonstrating that film level can also be used for the in vivo prediction of drug dissolution. The study confirmed that polymer molecular weight and its viscosity are the most important critical material attributes affecting drug dissolution (in vitro) and in vivo bioavailability (e.g. Cmax and AUC). Our research revealed that the nanoindentation technique can distinguish well between various types of polymers, classifying PEO as the most ductile and polyvinyl alcohol as the most brittle. Finally, our study provides an approach for the determination of exact physical attributes of PEO as a critical material attribute from clinically relevant data, and it therefore fulfills the basic principles of product development by Quality by Design.