Kinetics and structural modification of a commercial theophylline product after storage

The main objectives of this work were to determine the effect of storage ti me, temperature and pH of the medium on the in vitro release kinetics and m orphology of a commercial sustained-released dosage form of theophylline. T he formulation was stored at 35 degrees C for 16 months and at 45 degrees C for 8 months. The in vitro release tests were performed at pH 2, 4, 6 and 7.4. When the formulation was stored at 35 degrees C, significant differenc es (alpha = 0.05) were found in the values of the transport coefficient n a mong pH 2, 4, 6 and 7.4. At 45 degrees C, no significant differences among pH were found in the n value. Major modifications of the pellet membrane oc cur at 8 and 4 months when the formulation is stored at 35 and 45 degrees C , respectively. Storage of formulations under the two temperature condition s tested generated a modification in the model- independent parameters, e.g . dissolution efficiency at 8 h (DE8h), the amount of drug dissolved at 8 h (Qd(8h)), and the time at which 50% of the drug is dissolved (t(50%)). Reg ardless of the temperature (35 or 45 degrees C) or the pH assayed (2, 4, 6 and 7.4), an average decrease of approximately 20.6% is obtained for the di ssolution efficiency of the drug at the end of the trial. With respect to t (50%), an average increase of 38.5% is obtained for pH 2, 4; an average inc rease of 66.6% is obtained for pH 6 and 7.4.