Development of orally disintegrating tablet formulations and their pharmaceutical quality controls

Quetiapine is an atypical antipsychotic drug used for the treatment of schizophrenia and bipolar disorder. Quetiapine is commercialized as fumarate salt. Quetiapine fumarate (QF) is Biopharmaceutical Classification System (BCS) class II drug substance with its high permeability and low solubility. Orally disintegrating tablets (ODTs) are dosage forms that improve absorption in the gastrointestinal tract and enhance patient compliance. The purpose of this study is to develop QF, its inclusion complexes and its solid dispersions containing ODTs and to evaluate prepared ODTs in terms of in vitro pharmaceutical quality control parameters. Prior to formulation studies, 2-Hydroxypropyl-β-cyclodextrin, ɣ-cyclodextrin inclusion complexes and Soluplus® and PEG 2000 solid dispersions of QF were prepared by freze-drying method. Inclusion complexes and solid dispersions powders were evaluated for solubility, morphological properties and chemical interactions between active substance and polymers. According to the evaluations done of these tests, hydroxypropyl-β-cyclodextrin inclusion complex and Soluplus® solid dispersion were selected to do ODT formulation studies. Powder mixtures were prepared with selected inclusion complex, solid dispersion and tablet excipients. Flow properties ODT of these powder mixtures were evaluated using angle of repose, compressibility index and Hausner ratio. ODTs are obtained using these powder mixtures by direct compression method. ODTs containing only QF and tablet excipients were also developed. All ODTs were tested for diameter, thickness, crushing strength, disintegration time, average weight and in vitro dissolution.