Quality by design approach for development and optimization of Quetiapine Fumarate effervescent floating matrix tablets for improved oral bioavailability

摘要

The aim of the investigation was to develop and optimize the effervescent floating matrix tablets of Quetiapine Fumarate (QF) by using 23 factorial design. Amount of hydroxyl propyl methyl cellulose K4M (HPMC K4M (Ax)), amount of hydroxyl propyl methyl cellulose K15M (HPMC K45M (A2)) and amount of sodium bicarbonate (A3) (as gas-generating agent) were considered as independent variables and floating lag time (FLT, B^ (sec), percent drug release in 2 h (B2, Q2) and 6 h (B3, Q6) as dependent variables, respectively. Floating tablets of QF were prepared by effervescent technique using direct compression method. Drug-excipient compatibility studies were conducted by using DSC and FTIR techniques. The floating tablets were evaluated for physical characteristics, drug content, swelling index, in vitro buoyancy and in vitro release studies. Optimized formulation contains 25 mg of A1? 12.5 mg of A2 and 25 mg of A3 which resulted in 32 s of Bl5 32.89 ± 3.1 % of B2, and 73.61 ± 1.8 % of B3, respectively. DSC and FTIR studies revealed that no interaction between the drug and excipients in the developed formulation. The drug release followed Higuchi model and the Fickian transport. Physico-chemical stability studies revealed that the optimized formulation was stable for 90 days. Based on the physical evaluation and in vitro drug release characteristics, it was concluded that QF was suitable for incorporation into a floating drug delivery system.