Design and development of novel formulations with improved dissolution for aripiprazole

Abstract

For dissolution improvement of Aripiprazole, three different approaches were applied. In first approach, liquisolid compact technique was selected. Aripiprazole is used for bipolar disorder, which requires quick action. Formulation was prepared by using Cremophor RH 40 as a non-volatile solvent. Carrier material was selected Neusilin US2 and Coating material was selected was Aerosil 200. Optimization of formulation was performed by applying 32 full factorial design. The selected independent variables were drug concentration in liquid medication (X1) and carrier: coating ratio (R) (X2) and dependent variable are cumulative percentage drug release at 15 min (Y1) and angle of repose (Y2). The optimized liquid medication was converted into solid power form by using adsorbent material. Further it was converted to tablet form and then was evaluated for different parameters. In second approach, Solid self microemulsifying drug delivery system (S-SMEDDS) was developed. It contains capmul MCM EP as oil phase. D-optimal design was employed to optimise the formulation. The independent variables selected were X1 (amount of oil; capmul MCM EP), X2 (amount of surfactant; cremophor RH 40) and X3 (amount of co-surfactant; polyethylene Glycol 400). Systems were prepared and characterized for self-emulsification time, globule size and drug release. Optimized liquid formulations were formulated into free flowing powders (S-SMEDDS) by using liquisolid compact approach. Adsorption of liquid was carried out on the porous materials like Aerosil 200 and Neusilin US2 and then compressed into tablet. DSC and XRD study confirmed reduction in drug crystallinity. TEM analysis ensures spherical globules. Optimised formulation was compared with marketed formulation which demonstrate the improved dissolution characteristic of optimized formulation. In third approach, spherical agglomerates were prepared with use of acetone as good solvent, dichloromethane as bridging liquid, poloxamer 188 as surfactant and water as a poor solvent. Different tri