Quality-by-design based fabrication of febuxostat-loaded nanoemulsion: Statistical optimization, characterizations, permeability, and bioavailability studies

Vishal C Gurumukhi; Vivek P Sonawane; Ganesh G Tapadiya; Sanjaykumar B Bari; Sanjay J Surana; Shailesh S Chalikwar

doi:10.1016/j.heliyon.2023.e15404

Quality-by-design based fabrication of febuxostat-loaded nanoemulsion: Statistical optimization, characterizations, permeability, and bioavailability studies

Heliyon. 2023 Apr 18;9(4):e15404. doi: 10.1016/j.heliyon.2023.e15404. eCollection 2023 Apr.

Authors

Vishal C Gurumukhi¹, Vivek P Sonawane², Ganesh G Tapadiya¹, Sanjaykumar B Bari³, Sanjay J Surana⁴, Shailesh S Chalikwar⁴

Affiliations

¹ Department of Pharmaceutical Quality Assurance, Shreeyash Institute of Pharmaceutical Education and Research, Aurangabad 431010, Maharashtra, India.
² Department of IPQA, Micro Labs Ltd, Verna Industrial Estate, Goa 403722, India.
³ Department of Pharmaceutical Chemistry, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur 425 405, Maharashtra, India.
⁴ Department of Industrial Pharmacy and Pharmaceutical Quality Assurance, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425 405, Maharashtra, India.

Abstract

The present work deals with QbD-based development of FEB-loaded nanoemulsion (FEB-NE) in order to enhance bioavailability and permeability. In the beginning, the risk assessment was performed on different experimental variables using the Ishikawa diagram followed by FMEA study in order to find critical process parameter (CPP) and critical material attributes (CMAs). To build quality in nanoemulsion, the quality target product profiles (QTPP) and critical quality attributes (CQAs) were determined. The different batches of FEB-NE were produced by the microemulsification-probe sonication method. Effect of varying levels of independent variables such as oil concentration (X₁), S_mix concentration (X₃), and amplitude (X₃) on responses such as globule size (Y₁), zeta potential (Y₂), and entrapment efficiency (Y₃) were studied using Box-Behnken design (BDD). FEB-NE formulation was optimized using a graphical and numerical method. The optimized formulation concentrations and their responses (CQAs) were located as design space in an overlay plot. The spherical shapes of globules were visualized by surface morphology using AFM and TEM. In vitro dissolution study showed 93.32% drug release from the optimized FEB-NE formulation. The drug release mechanism followed by the formulation was the Higuchi-matrix kinetics with a regression coefficient of 0.9236 (R²). FEB-NE showed enhanced permeability using PAMPA (artificial non-cell membrane) and everted gut sac model method. The developed optimized FEB-NE exhibited the enhancement of bioavailability by 2.48 fold as compared to FEB-suspension using Wistar rats suggesting improvement of solubility of a lipophilic drug. The optimized batch remained stable for 90 days at 4 °C and 25 °C. Thus, QbD-based development of FEB-NE can be useful for a better perspective on a commercial scale.

Keywords: Bioavailability; Box behnken design; Febuxostat; Quality by design.