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

This study investigated the influence of the rheological properties of hydr oxypropylcellulose (HPC) gels on the in vitro release of theophylline inclu ded in the gel at 0.2 g/l. Experiments were performed with six HPC varietie s (mean molecular weight between 5 x 10(5) and 1.2 x 10(6), nominal viscosi ty between 100 and 4000 mPa.s) at concentrations of 0-2% (w/w). Theophyllin e 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 predicte d 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, how ever, 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) w ith latex microspheres (162 nm diameter) were considerably lower than the m acroviscosities determined by capillary viscometry, and similar to microvis cosities estimated on the basis of theophylline diffusion. Nevertheless, ma croviscosity was correlated with microviscosity, suggesting that it is of v alue for approximate estimates of rates of diffusion of theophylline from H PC gels. (C) 1999 Elsevier Science B.V. All rights reserved.