Acta Pharm. 67 (2017) 53-70
Original research paper
Formulation
and pharmaceutical development of quetiapine fumarate sustained release matrix tablets using a QbD approach
ALEXANDRU
GÂVAN, ALINA PORFIRE, CRISTINA MARINA and
IOAN TOMUÞÃ
aporfire@umfcluj.ro
University of Medicine and Pharmacy „Iuliu Hatieganu”, Faculty of
Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics,
Cluj-Napoca, Romania
Accepted December 3, 2016
Published online December
8, 2016
The main objective of the present study was to
apply QbD methodology in the development of
once-a-day sustained release quetiapine tablets. The
quality target product profile (QTPP) was defined after the pharmaceutical
properties and kinetic release of the innovator product, Seroquel
XR 200 mg. For the D-optimal experimental design, the level and ratio of matrix
forming agents and the type of extragranular
diluent were chosen as independent inputs, which
represented critical formulation factors. The critical quality attributes (CQAs)
studied were the cumulative percentages of quetiapine
released after certain time intervals. After the analysis of the experimental
design, optimal formulas and the design space were defined. Optimal formulas demonstrated
zero-order release kinetics and a dissolution profile similar to the innovator
product, with f2 values of
74.53 and 83.74. It was concluded that the QbD
approach allowed fast development of sustained release tablets with similar
dissolution behavior as the innovator product.
Keywords: quality by design, design of
experiments, sustained release, hydrophilic matrix, quetiapine