Microviscosity of hydroxypropylcellulose gels as a basis for prediction of drug diffusion rates

This study investigated the influence of the rheological properties of hydroxypropylcellulose (HPC) gels on the in vitro release of theophylline included in the gel at 0.2 g/l. Experiments were performed with six HPC varieties (mean molecular weight between 5 x 10(5) and 1.2 x 10(6), nominal viscosity between 100 and 4000 mPa.s) at concentrations of 0-2% (w/w). Theophylline diffusion coefficients at 37 degrees C ranged from 3.5 x 10(-7) to 1.1 x 10(-3) cm(2)/min, and were in all cases markedly higher than those predicted on the basis of gel macroviscosity as determined by capillary viscometry. In general, the theophylline diffusion coefficient declined exponentially with HPC concentration; in the case of the lowest-molecular-weight HPC, however, the diffusion coefficient remained constant to HPC concentrations of up to 0.8%, probably because of the high entanglement concentration of the HPC. Gel microviscosities as determined by dynamic light scattering (DLS) with latex microspheres (162 nm diameter) were considerably lower than the macroviscosities determined by capillary viscometry, and similar to microviscosities estimated on the basis of theophylline diffusion. Nevertheless, macroviscosity was correlated with microviscosity, suggesting that it is of value for approximate estimates of rates of diffusion of theophylline from HPC gels. (C) 1999 Elsevier Science B.V. All rights reserved.