In-vitro and pharmacodynamic characterization of solidified self microemulsified system of quetiapine fumarate

Abstract

Quetiapine fumarate has possessed low solubility and extremely poor bioavailability, which restricts its oral administration. In order to address this concern, microemulsification technique was envisaged. Solubility of quetiapine was assessed in various liquid vehicles (oils, surfactants and cosurfactants) for the selection of carriers in self microemulsifying drug delivery system (SMEDDS) formulation. Microemulsion region was identified from the pseudoternary phase diagram. Quetiapine was loaded in preconcetrates of the predetermined microemulsion region. Quetiapine loaded SMEDDS were characterized for FTIR, pH, viscosity, zeta potential, and evaluated for drug content, in-vitro dissolution, in-vitro diffusion, and ex-vivo permeation. Optimized liquid SMEDDS were renewed into S-SMEDDS by adsorption and melt granulation technique. Formulated S-SMEDDS were characterized for micromeritics, DSC, SEM, and evaluated for drug content, reconstitution time, drug release, stability and anti-psychotic activity in animals for amphetamine induced stereotypy and swimming normalization test. The formulations of O11, O13, C6 and C10 liquid SMEDDS had shown drug release of 92, 94.16, 68.59 and 55.03% respectively at the end of 1 h. S-SMEDDS exhibited good micromeritics with a drug content of 80 to 90% and released drug up to 96%. AO13 of S-SMEDDS had 1.2 years of shelf life and exhibited better anti-psychotic activity owing to enhanced biomembrane permeation in the presence of tweens as surfactants. The spontaneous formation of microemulsion from adsorption based S-SMEDDS resulted in hasty drug release. Thus the results of the study indicated that self microemulsification of quetiapine and subsequent solidification is the better alternative in affording optimal pharmacotherapy of psychosis.