Abstract

FORMULATION AND IN VIVO EVALUATION OF RISPERIDONE SPHERICAL AGGLOMERATES PREPARED FOR EARLIER ABSORPTION OF RISPERIDONE

Moataz Farid* and Mohamed Jaffer

Abstract

Risperidone (RES) is a second generation antipsychotic drug with potent serotonin-5HT2 and potent dopamine-D2 antagonistic properties. RES belongs to class II of the Biopharmaceutical Classification System (BCS) meaning that it has low water solubility and high permeability and the dissolution rate is the limiting factor for its absorption. The main aim of this study was to improve the solubility, the dissolution rate and hence the bioavailability of risperidone using spherical agglomeration technique with methanol, water and chloroform as good solvent, poor solvent and bridging liquid, respectively. The quasi emulsion solvent diffusion technique was used as a method for spherical agglomeration. Polyethylene Glycol 4000 and inutec SP1 were used as hydrophilic polymer in agglomeration process. The agglomerated crystals were evaluated by water solubility, drug content, in-vitro release studies, Powder X- Ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infra Red Spectroscopy (FT-IR) and Particle size analysis. The water solubility of all RES agglomerated crystals was improved, it was found to be in the range of 15.6 ± 0.27 to 188.2 ± 0.2 μg/ml when compared with the solubility of raw risperidone 2.16 ± 0.12 μg /ml. The dissolution rate of risperidone agglomerates within 60 minutes increased to about 3 - 6 folds in simulated gastric fluid. DSC and FT-IR outcome showed no chemical alteration in the recrystallized drug. DSC and PXRD studies showed that crystallinity of RES was retained in all of the prepared agglomerated crystals. The in vivo activity of F2 (showing highest dissolution rate in simulated gastric fluid) was assessed in mice. The selected formulae showed significantly higher activity in comparison to the pure drug and control.

Keywords: Risperidone, Spherical agglomeration, Solubility, Dissolution rate.