Atenolol release from hydrophilic matrix tablets with hydroxypropylmethylcellulose (HPMC) mixtures as gelling agent: Effects of the viscosity of the HPMC mixture

The aims of this study were to assess the potential value of hydroxypropylmethylcellulose (HPMC) mixtures as gelling agents in matrix tablets for hydrosoluble drugs, and to investigate relationships between gelling agent viscosity and the kinetics of drug release from such tablets. Experiments were carried out with Methocel(R) K100LV (an HPMC with nominal viscosity of 100 cP) and Methocel(R) K100M (an HPMC with nominal viscosity of 100 000 cP). Rheological characterization of 2% dispersions of the polymers, and of 30:70, 50:50 and 70:30 mixtures, indicated that it is possible to obtain a wide range of rheological behaviours by mixing K100LV and K100M, and that the two polymers display rheological antagonism. Trials were carried out with atenolol tablets made with 40% or 80% gelling agent (i.e. K100LV, K100M or one of the K100LV:K100M mixtures). Analysis of drug dissolution profiles in 0.1 N HCl, on the basis of Higuchi's model and the equation of Korsmeyer and coworkers, indicated that drug release was in all cases diffusion-limited. A negative relationship was observed between the Higuchi constant for each tablet type and the apparent viscosity of the corresponding gelling agent in aqueous dispersion. In addition, apparent viscosity was negatively related to rate of attrition, suggesting that the observed relationship between the Higuchi constant and apparent viscosity is a reflection of differences in attrition resistance.