Title:Formulation Development and Optimization of Blonanserin Liquid
SMEDDS using D-Optimal Mixture Design
Volume: 17
Issue: 4
Author(s): Sohansinh Vaghela*, Sunita Chaudhary and Ankit Chaudhary
Affiliation:
- Department of Pharmacy, Gujarat Technological University, Ahmedabad, India
- Department of Quality Assurance, Saraswati Institute
of Pharmaceutical Sciences, Gandhinagar, Gujarat, India
Keywords:
D-optimal mixture design, SMEDDS, in vitro diffusion, blonanserin, solubility enhancement, co-surfactant.
Abstract:
Background: Blonanserin is an atypical antipsychotic potent antagonist of dopamine-D2
and D3 receptors with low aqueous solubility BCS class II drugs.
Objective: The present research aims to develop and optimize the Blonanserin-loaded liquid selfmicro
emulsifying drug delivery system (SMEDDS) to improve its in vitro drug release by D-optimal
mixture design.
Methods: Saturation solubility of Blonanserin was checked in various oils, surfactants, and cosurfactants.
The pseudo-ternary phase diagram was developed to identify the region of the microemulsion.
Trial batches were designed to determine dependent and independent variables in the formulation. DOptimal
Mixture design applies for optimization and minimized trials. The amount of oil(X1), surfactant(
X2), and co-surfactant(X3) were selected as independent variables, and solubility(Y1) and in vitro
percentage cumulative drug release(Y2) and size of globule(Y3) after 250 times dilution were selected
as the dependant variable. The level of the independent variables in the design will be selected based
on the drug's phase diagram, trial batches, and solubility. The developed SMEDDS was then evaluated
for globule size, transparency, self-emulsification time, in vitro dissolution, and relative dissolution of
the final formulation with marketed products and a pure drug.
Results: BLN shows the highest solubility in (1:1) Captex 200P: Capmul MCM (oil), Tween 20 (surfactant),
and Ethanol (cosurfactant). Trial batches were shown at 1:9, 2:8, and 3:7 oil to surfactant and
cosurfactant ratios suitable for optimization. Optimization using a D-optimal mixture design gives 11
run batches and the resulting surface and contour plot suggest the best design space. The optimized
formula given by the mixture design of the target formulation had maximum drug solubility, maximum
drug release, and minimum globule size. Optimized formula containing Blonanserin, Captex
200P: Capmul MCM (1:1) Mixture (23% v/v), Tween 80 (57% v/v), and Ethanol (20% v/v) having
94.72% in vitro diffusion within 30 min with 21 nm globule size. Optimized liquid SMEDDS have a
higher in-vitro diffusion rate than marketed products and pure drugs.
Conclusion: Blonanserin liquid SMEDDS was successfully developed with high solubility, nanoglobule
size, and improvement in in-vitro diffusion rate and vice versa for improvement in bioavailability
of the drug.
