PREPARATION AND SOLID STATE CHARACTERIZATION OF NANOCRYSTALS FOR SOLUBILITY ENHANCEMENT OF QUETIAPINE FUMARATE
Keywords:Quetiapine Fumarate, Nanosuspension, Wet media milling, Lyophilized nanoparticles
Objective: Quetiapine fumarate (QF) has poor water solubility and its oral bioavailability is observed to be 9% . The objective of the present work is to prepare QF nanoparticles by wet media milling (WMM) and explore on the improvement in solubility with the aim of dose reduction and minimizing the side effects associated with its oral administration.
Methods: Nanoparticle of QF were prepared by WMM using sodiumlaurylsulphate (SLS), polyvinylpyrrolidone (PVP), hydroxypropylcellulose (HPC) and Hydroxypropylmethylcellulose (HPMC) as surface stabilizers. The nanosuspensions obtained were characterized for its mean particle size (MPS), zeta-potential (ZP) and Polydispersity-index (PI). Further lyophilized nanoparticles were characterized for MPS, ZP, PI, saturation solubility (SS), X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), Infra-Red (IR) and Scanning electron Microscopy (SEM).
Results: The MPS of the nanosuspensions obtained after 1 hour WMM and its lyophilized nanoparticlesis observed to be less than 1000 nm with PI ranges from 0.2 to 0.6 and negative ZP ranging from -30 to -36 mV. Lyophilized nanoparticles have shown significant improvement in SS when compared to plain drug. XRD and DSC have shown absence of the crystalline peaks and endotherm of QF respectively, indicating loss of its crystallinity. IR spectra showed no change in position of bands thus drug is compatible with surface stabilizers used. SEM photographs confirmed the formation of nanoparticles.
Conclusion: From the above results it has been concluded that by subjecting QF to WMM, QF nanoparticles were obtained with significant improvement in saturation solubility and drug losing its crystalline nature when compared to plain drug.
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