Page 27 - 2021

Ph.D.
(Pharmacy)
DESIGN AND DEVELOPMENT OF NOVEL FORMULATIONS WITH
IMPROVED DISSOLUTION FOR ARIPIPRAZOLE

Ph.D. Scholar : Rao Shruti Sudeshkumar
Research Supervisor : Dr. B. G. Prajapati

Regi. No.: 15146021004
Abstract :
For the dissolution improvement of Aripiprazole, three different approaches were applied.
In the first approach, liquisolid compact technique was selected. Aripiprazole is used for
bipolar disorder, which requires quick action. The 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 the 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 variables 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 the second approach, a Solid self micro emulsifying 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 porous
materials like Aerosil 200 and Neusilin US2 and then compressed into tablet. DSC and
XRD studies confirmed a reduction in drug crystallinity. TEM analysis ensures spherical
globules. Optimised formulation was compared with a marketed formulation which
demonstrates the improved dissolution characteristic of optimized formulation. In third
approach, spherical agglomerates were prepared with the use of acetone as a good
solvent, dichloromethane as a bridging liquid, poloxamer 188 as surfactant, and water as
a poor solvent. Different trial batches were prepared for the selection of factors. Box
Behnken design was applied to optimize the formulation. Acetone (7.7% v/v),
dichloromethane (2.56 %v/v), poloxamer (1 %w/v) were found to be optimum
concentrations using the design. The optimized formulation was evaluated for sphericity,
dissolution rate, Scanning electron microscopy (SEM) study, micromeritics properties.
The optimized spherical agglomerates were compressed to form a tablet. The final

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