Impact of hydrophilic binders on stability of lipid-based sustained release matrices of quetiapine fumarate by the continuous twin screw melt granulation technique

Dose dumping is the major drawback of sustained release (SR) matrices. The current research aimed to develop the stable lipid-based SR matrices of quetiapine fumarate (QTF) using Geleol (TM) (glyceryl monostearate; GMS) as the lipid matrix carrier and Klucel (TM) EF (HPC EF), Kollidon (R) VA64, and Kollidon (R) 12PF as hydrophilic binders. Formulations were developed using advanced twin screw melt granulation (TSMG) approach and the direct compression (DC) technique. Compared with the blends of DC, the granules of TSMG exhibited improved flow properties and tabletability. Solid-state characterization by differential scanning calorimetry of the prepared granules exhibited the crystalline nature of the lipid. Fourier transform infrared spectroscopy demonstrated no interaction between the formulation ingredients. The compressed matrices of TSMG and DC resulted in the sustained release of a drug over 16-24 h. Upon storage under accelerated conditions for 6 months, the matrices of TSMG retained their sustained release characteristics with no dose dumping in alcohol, whereas the matrices of DC resulted in the dose dumping of the drug attributing to the loss of matrix integrity and phase separation of lipid. Thus, it is concluded that the uniform distribution of a softened binder into a molten lipid carrier results in the stable matrices of TSMG. (C) 2021 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.