Preparation and evaluation of theophylline sustained-release tablets

Formulations were prepared containing 50% theophylline; 0%, 5%, 10%, 20%, 30%, or 49.5% of a new sustained-release agent (Carbopol(R) 974P); 0.5% lubricant, with the remainder of the formula consisting of spray-dried lactose. Similarly, a formulation containing 30% Carbopol 934P was prepared for comparative study. The tablets produced showed good mechanical properties. The disintegration time of the tablets was dependent on the type and percentage of the sustained-release agent as well as the pH of the medium. The drug release profiles were consistent with the disintegration time; increasing the percent of Carbopol 974P in the tablet and holding its weight constant resulted in a decrease in drug release rate. Approximately 10% Carbopol 974P provided the same sustained-release mechanism as 30% Carbopol 934P without tablet sticking during compression. Carbopol 974P matrices exhibited release profiles which were best described by mixed zero-order and Higuchi linear square root of time relationships. This means that mixed barrier and matrix diffusion-controlled mechanisms were operative.