Integrating Quality by Design Principles for Elevating Bioavailability of Candesartan Cilexetil in Fast-dissolving Tablets

Abstract

Aim: The present research was aimed to increase the bioavailability of Candesartan cilexetil by integrating
efficient super disintegrating agents applying the principles of quality by design. Materials and Methods:
This study optimized fast dissolving tablets containing Candesartan cilexetil by integrating efficient super
disintegrating agents (Isabgol husk, Potato starch, F melt C) through a direct compression method. Utilizing Design
of Expert version 13.0 with a response surface methodology, formulations (CC1-CC15) were systematically
developed. The influence of super disintegrates on key parameters - disintegration time (Y1), drug release at
15 min (Y2), and drug release at 30 minutes (Y3) - was extensively studied to enhance Candesartan cilexetil’s
dissolution properties. Results and Discussion: Comprehensive evaluation of pre- and post-compressional
factors, coupled with robust in-vitro dissolution analysis, highlighted formulation CC12’s excellence, featuring
rapid disintegration and maximal drug release within specified timeframes. Utilizing the DD solver guided by
regression coefficients (r2), Akaike Information Criterion (AIC), and model selection criteria (MSC), kinetics
and release mechanisms were elucidated. CC12 exhibited a fickian diffusion mechanism, substantiating its
robust drug release profile. Additionally, shelf-life evaluation as per ICH guidelines and a comparative analysis
employing the similarity factor (f2) with Atacand were conducted. Stability studies, assessed via ANOVA,
indicated insignificant differences (P > 0.05) during storage. In summary, this research optimally enhanced
Candesartan cilexetil’s dissolution via proficiently formulated fast dissolving tablets. The strategic integration
of super disintegrating agents, driven by Design of Expert version 13.0, yielded CC12 as an optimal candidate
with rapid disintegration and superior drug release. Elucidation of release kinetics and mechanisms further
fortified performance assessment. Thorough stability and similarity evaluations underscored the potential of this
optimized formulation for improved therapeutic outcomes. Conclusion: Fast dissolving tablets of C and esartan
cilexetil were developed by optimizing selected independent variables to improve the dissolution profile. The
presence of soluble polymers like Isabgol husk, potato starch and F melt C, acting as super disintegrants, played
a significant role in enhancing solubility.