Drug release from hydroxypropylcellulose gels cannot be statistically predicted from their viscometric and initial viscoelastic properties

Abstract

This study questioned whether rheological properties can predict drug (metronidazole) release from Hydroxypropylcellulose (HPC) platforms. Viscometric and viscoelastic properties of aqueous, alcohols/diols and mixed solvent HPC solutions and gels were determined using viscometry and oscillatory analysis. Drug release was conducted at pH 7.4 under sink conditions. Relationships between rheological parameters and drug release were modelled using multiple linear stepwise regression. Viscometry identified ethanol and water as good solvents for HPC. Diol solvents were predicted to exhibit greater interactions with HPC (COSMO modelling) but possessed lowest intrinsic viscosities. Pentanediol or ethylene glycol prepared gels exhibited greatest elasticity. No relationships were observed between dilute solution properties and initial gel viscoelasticity. Drug release from HPC gels occurred via gel erosion and diffusion. No relationships were observed between initial gel viscoelasticity and drug release and thus, for gel platforms that undergo erosion in aqueous media, drug release cannot be predicted from initial gel viscoelasticity.