Magnetic resonance imaging was used to study the behavior of the gel layer thickness in hydroxypropyl methyl cellulose (HPMC) matrices loaded with different amounts of soluble tetracycline hydrochloride. The time dependence of the diffusion front, effective T2, and proton-density analysis clearly indicates a Case II diffusion mechanism in the system composed of water solution of hydrochloric acid (pH = 2) and HPMC. The solvent penetration front was used to describe the swelling properties as well as the integrity of the HPMC matrices. The results show that the tetracycline hydrochloride decreases the resistance of the HPMC network structure against the movement of solvent molecules. On the other hand the swelling properties of the matrix increase with the amount of drug in the matrix.