The aim of the study was to evaluate the effect of systematic agitation, increasing ionic strength and gel strength on drug release from a gel-forming matrix (HPMC E10M, E4M and E50LV) using USP type III Bio-Dis apparatus with theophylline as a model drug. The triboelectric charging; particle sizing, water content, true density and SEM of all the hypromellose grades, theophylline and formulated blends were characterised. The results showed that balanced inter-particulate forces exist between drug particles and the excipient surface and this enabled optimum charge to mass ratio to be measured. Agitation and ionic strength affected drug release from E50LV and E4M tablet matrices in comparison to the E10M tablet matrices. Drug release increased substantially when water was used as the dissolution media relative to media at pH 1.2 (containing 0.4 M NaCl). The results showed all f2 values for the E10M tablet matrices were above 50 suggesting the drug release from these tablet matrices to be similar. Rheological data also explained the different drug release behaviour with the stress required to yield/erode being 1 Pa, 150 Pa, and 320 Pa, for the E50LV, E4M and E10M respectively. The stiffness of the gel was also found to be varied from 2.5 Pa, 176.2 Pa and 408.3 Pa for the E50LV, E4M and E10M respectively. The lower G′ value can be explained by a softer gel being formed after tablet introduction into the dissolution media thereby indicating faster drug release.