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After oral administration, drug absorption rate is recognized to be dependent on two major factors: dissolution and intestinal cells permeability. Caco-2 monolayer cells have been largely used as a permeation study model. In this study, a numerical approach funded on an exponential first-order time relationship was tested to compare immediate- and controlled-release tablets of theophylline using a dissolution-permeation system. The dissolution performance using USP II paddle apparatus was coupled to the permeability studies investigated in Caco-2 cell monolayers. The dissolved samples were taken at different times; their pH and osmolarity were adjusted to render them suitable to Caco-2 permeability studies (osmolarity = 300 mosm, pH = 7.4). The experimental data show that the dissolution fits the exponential first-order relationship rate. The permeability values were in a range of 4.45 10 - 6 –5.28 10 - 6 cm/s, and percentages of absorbed drug dose were dependent on the fraction initially present in the donor compartment, indicating that absorption of theophylline was dissolution rate limited. Plotting experimental absorbed fractions (F a ) against experimental dissolved fractions (F d ) show that permeation is the rate-limiting step in drug absorption process in the extended release form of theophylline. Our results demonstrate a general agreement between observed F a /F d relationships and theoretical F a /F d relationships obtained with our approach funded on dissolution and permeation behavior. We concluded that the couple dissolution-caco-2 system could be a useful tool to characterize intestinal permeation for a new formulation of a drug compared with the conventional one. [ABSTRACT FROM AUTHOR]