Development of Extended Release Pellets of Quetiapine Fumarate by using HPMC and Eudragit RSPO

The aim of the present investigation was to develope extended release pellets of quetiapine fumarate. The combinations of hydrophilic (hydroxypropyl methylcellulose; HPMC K100M) and hydrophobic (Eudragit RSPO) extended release excipients were utilized for the development. The amount of HPMC K100M (X₁), amount of Eudragit RSPO (X₂), and amount of acidifier (anhydrous citric acid) (X₃) were chosen as independent variables. These variables were optimized employing a simplex lattice design. The selected dependent variables were the cumulative percentage of quetiapine fumarate dissolved at 1 (Y₁), 6 (Y₂), 12 (Y₃) and 20 hr (Y₄). The in vitro drug release study was carried out in citrate buffer (pH 4.8) for 5 hr and thereafter the study was conducted in phosphate buffer (pH 6.6) up to 20 hours. Optimization was performed for the independent variables X₁, X₂ and X₃ using the target ranges; 9%≤Y₁≤14%; 56%≤Y₂≤60%; 76%≤Y₃≤80%; 90%≤Y₄≤100% (selected on the basis of NDA documents of the innovator). The optimized amounts of HPMC K100M (X₁), Eudragit RSPO (X₂) and anhydrous citric acid (X₃) were 131, 100 and 54 mg respectively. Extended release pellets of the optimized formulation showed a release profile that was close to the values of innovator drug product (Seroquel XR^®). The drug was released as per first order from the optimized formulation.