Formulation Development, in-vitro and in-vivo evaluation of novel solid oral dosage form containing Quetiapine nanoparticles.

Lakshmi Prasanna Gubbala, Srinivas Arutla, Vobalaboina Venkateshwarlu

Abstract


Poorly water soluble drugs such as quetiapine fumarate (QF) offer challenges in developing a solid dosage form such as tablets with adequate bioavailability. The objective of the present work is to develop a solid dosage form for quetiapine nanoparticles in order to increase the saturation solubility, rate of dissolution so that the oral bioavailability is enhanced. Quetiapine fumarate is a BCS class II drug, hence its oral bioavailability is dissolution limited. To enhance the oral bioavailability a nanoparticle formulation of QF was prepared by using high pressure homogenization. The nanosuspension prepared was converted into dry powder by using spray drying. The nanosuspension and spray dried nanoparticles are characterized for particle size, polydispersity index, zeta potential, saturation solubility, drug content, dissolution rate, solid state characterization such as X-ray diffraction(XRD), Differential scanning calorimetry(DSC), infrared(IR), scanning electron microscopy(SEM), transmission electron microscopy(TEM). The spray dried nanoparticles were blended with excipients to convert into solid dosage form such as tablets. The compressed tablets were evaluated for physical parameters, assay and dissolution was compared with the commercial QF formulation. Solid state characterization data showed loss of drug crystallinity after homogenization. The novel dosage form has shown significant increase in the rate of dissolution when compared to microparticle formulation in discriminating medium. In-vivo studies have shown that the rate and extent of absorption of nanoparticle formulation was significantly high when compared to its microparticle formulation when administered in rats.


Keywords


Quetiapine Fumarate, Nanoparticles, high pressure homogenization, Particle size

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