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Quality by Design enabled anti-hypertensive Floating drug delivery system by Risk assessment and Design of Experiment (DoE) – In vitro – In vivo correlation studies

Author(s):

Mounika Chidurala* and Raveendra Reddy J  

Abstract:


Background: The present research aimed to develop and optimize extended-release floating tablets of Sacubitril and Valsartan through Quality by Design (QbD) approach. Risk analysis by formulation assessment and process parameters showed that optimizing the levels of the polymer will minimize 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, whereas Ethylcellulose had a negative effect on Floating time, drug release at 2 h, drug release at 12 h and, 50% 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 healthy rabbit’s stomach confirmed the floating behavior for more than 12 h. In vivo pharmacokinetic studies in rabbits showed 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 de-convolution 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 confirmed 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.

Keywords:

Floating time; Ethyl Cellulose; Quality by design; X-ray imaging; IVIVC

Affiliation:

Research scholar, Pharmaceutical Sciences, Jawaharlal Nehru Technological University Anantapur, Anantapuramu-515721, Raghavendra Institute of Pharmaceutical Education and Research, K. R. Palli cross, Chiyyedu Post, Anantapuramu - 515721, Andhra Pradesh



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