QbD Assisted Fabrication of Optimized Mouth Dissolving Film Formulation of

Ivabradine Hydrochloride

Ghanshyam Patel, Upendra Bhadoriya, Nitin Dubey

IPS Academy College of Pharmacy, Indore (M.P.), India

ABSTRACT

Objective: The present study was aimed to design and optimize Ivabradine Hydrochloride
loaded mouth dissolving film (MDF) formulation for enhanced bioavailability and effective
oral delivery.

Material: Design of experiment (DoE) based formulation and optimization was done by
three-factor, three-level Box–Behnken design approach. The excipients comprise polymer,
plasticizer, and surfactant as an independent variables and thickness, folding endurance, and
% drug release as response variables. The suggested optimized formulation of Ivabradine HCl
loaded MDF with highest desirability was prepared by solvent casting method and
characterized for all desired critical quality attributes (CQAs) and stability studies.

Results: The optimized MDF formulation exhibited experimentally observed responses close
to the predicted values, thickness (99.2 μm), folding endurance (209 folds), and % drug
release (95.90%). The solid-state characterization studies by SEM, DSC, FT-IR, and XRD
revealed excellent film characteristics.

Conclusion: The developed Ivabradine HCl loaded MDF formulation possessed all
recommended CQAs in optimal range with enhanced bioavailability and remained physically
stable.

Keywords: Optimization, Bioavailability, Mouth dissolving film, Design of Experiments,

Ivabradine HCl.
GRAPHICAL ABSTRACT

Selection of
Variables

Independent Response
Polymer (mg) Thickness (μm)
Plasticizer (mg) Folding endurance (folds)
Surfactant (mg) In-vitro Drug releases (%)
Formulation Optimization Box–Behnken design representing
using QbD Approach independent variables at three levels
(–1, 0, +1)
Response Surface Analysis of MDF Formulations

Fabrication of MDF Formulations

SEM

Optimized MDF Formulation

DSC

FTIR

% Drug
Prediction of Optimized MDF Formulation releases
100

90
% Drug release

80

70
MQA3016
60

50

40

30

20

0
XRD
2 4 6
Time (minutes)
8 10