Abstract: In order to study the effect of in vitro parameters on the theophylline release from the hydrogel system of atactic-PVA/NaCl/H2O, in vitro parameters such as agitators, rotation speed, release medium and release temperature were evaluated. Theophylline release was studied for a period of 750 min using paddle and propeller agitator, rotation speed (25, 50, 100 and 150 rpm), release medium (simulated fluids pH 1.2, 7.5 and phosphate buffer pH 8.5 with 0.05 M at 37°C) and release temperatures (27, 37 and 47°C). SEM and DSC studies were performed to evaluate the surface morphology and heat capacity as well as melting temperatures of the hydrogels affected by various simulated fluids and phosphate buffer. A regular Fickian diffusion was found (Higuchi Model) for first 60 to 70% release. A faster release rate was found in paddle rotation than that of propeller one. Among the release medium comparatively high release rate in extremely low pH (1.2) and near about same release rate in distilled water, pH 7.5 and pH 8.5 were found. DSC thermogram of these treated xerogels showed low melting temperature as well as high heat capacity of pH 1.2 sample than that of others. Rotation speed had a little effect on release rate but the diffusion exponent. It decreased linearly with increasing rotation speed. On the other hand release rate increased proportionally to temperature where diffusion exponent decreased with increasing temperature in a parabolic fashion. Theophylline release behavior was regular Fickian diffusion (Higuchi Model) irrespective of in vitro conditions studied here. However release rate, diffusion exponent, kinetic constant and diffusion co-efficient vary with rotator type, rotation speed, release medium and temperature.