Title:Quality by Design Enabled Anti-hypertensive Floating Drug Delivery System by Risk Assessment and Design of Experiment (DoE) - In Vitro - In Vivo Correlation Studies
Volume: 16
Issue: 4
Author(s): Mounika Chidurala*Raveendra Reddy Jutur
Affiliation:
- Pharmaceutical Sciences, Jawaharlal Nehru Technological University Anantapur, Anantapuramu-515721, Andhra Pradesh,India
Keywords:
Floating time, ethyl cellulose, quality by design, x-ray imaging, IVIVC, drug.
Abstract:
Background: The present research aimed to develop and optimize extended-release floating
tablets of Sacubitril and Valsartan by Quality by Design (QbD) approach.
Methods: Risk analysis by formulation assessment and process parameters showed that optimizing the
levels of the polymer will minimize the high risk to meet the target profile. A two (2) level three (3)
full factorial experimental design along with midpoints was carefully chosen for optimization and statistical
analysis. Based on the literature, the independent and dependent variables were selected.
Results: HPMC K100, Carbopol 934P had a positive effect, Ethyl cellulose with the negative effect on
Floating time, Drug release at 2 h, Drug release at 12 h and, t50% responses. Drug release kinetics followed
the first-order release with Higuchi and fickian diffusion. Contour and overlay plots were utilized
for an assortment of design space and optimized formula. ANOVA results of all the factors exhibited
significance at p < 0.05. Abdominal X-ray imaging of the optimized tablets on a healthy rabbit’s
stomach confirmed the floating behavior for more than 12 h. In vivo pharmacokinetic studies in
rabbits have shown that the optimized formulation exhibited prolonged and extended drug release with
improved Cmax, tmax, AUCo-t, and t1/2 of test product when compared to marketed product. IVIVC
model was developed by using dissolution data of in vitro and pharmacokinetics data of in-vivo by deconvolution
method (Wagner-Nelson method).
Conclusion: The Quality by Design implementation in the formulation and optimization abridged the
number of trials to produce a cost-effective formula. In vivo studies have demonstrated that the formula
was successfully developed with extended floating time (12 h) and drug release by risk analysis and
experimental designs. Level A correlation was observed, which confirmed a good correlation between
in vitro and in vivo data.
