Development of a sustained release acetaminophen-hypromellose matrix tablet and the evaluation of the effects of insoluble additives on the drug release kinetics

An Acetaminophen sustained release tablet is a convenient dosage form to avoid frequent dosing and to achieve patient compliance. A dose of acetaminophen (650--1000 mg) 4--6 times per day for adults is fairly high, making it difficult to control its release from a sustained release dosage form. Additives used in the tablet can affect the rate and mechanism of drug release from the tablet. The current work is intended to develop a sustained release acetaminophen tablet and to evaluate the effect of additives on the rate and mechanism of drug release from the acetaminophen-hypromellose tablet matrix. It was hypothesized that water insoluble additives delay the movement of solvent front through the matrix thereby reducing the dissolution rate. Experiments were designed to develop a sustained release acetaminophen-hypromellose matrix tablet by systematically changing the hypromellose content. Effect of water insoluble additives like corn starch, pregelatinized starch and dicalcium phosphate on dissolution rate of acetamoinophen from the matrix was evaluated. Based on the first order release rate constant and Higuchi constant, it was shown that water insoluble additives reduced the rate of drug release from the tablet matrix. The drug release is inversely related to the amount of water insoluble additives in the formulation. Based on the release exponent 'n' (n<0.89) from the power law, it was shown that additives shifted the mechanism of drug release from anomalous transport towards Fickian diffusion.