Optimization of gliclazide loaded alginate-gelatin beads employing central composite design

Abstract

Objective: The aim of this study was to optimize the formulation of alginate-gelatin (AL-GL) beads containing gliclazide (GLZ) employing design of experiments (DOE).Significance: DOE enabled identification of the interaction between the studied factors, deep understanding of GLZ release pattern and acceleration of the optimization process.Methods: A three-factor, three-level face centered design was employed. The effects of GLZ content (GLZ%, X1), polymer ratio (AL:GL ratio, X2), crosslinker concentration (glutaraldehyde, GA%, X3), and their interaction on incorporation efficiency (IE) and release rate were studied. The optimized formulation was prepared using numerical optimization and evaluated by DSC, FT-IR, SEM and release rate studies.Results: Increasing GA% (X3) decreased IE (Y1) with the highest magnitude of effect among the studied factors. On the other hand, increasing alginate content in AL:GL ratio (X2) increased IE (Y1). The amount of GLZ released Q0.5h, Q2h(pH 1.2) and Q4h(pH 7.4) decreased by increasing GLZ% (X1) and AL:GL ratio (X2). Both drug content and AL:GL ratio appeared to affect water penetration into the gel matrix and drug release. Generally, there was a direct relationship between GA% (X3) and GLZ release in pH 1.2 (Q0.5h and Q2h). However, in pH 7.4 (Q4h), increasing GA% decreased GLZ release. In addition, increasing GA% caused deviation from zero-order release model. The actual responses of the optimized formulation were in close agreement with the predicted ones.Conclusion: The selected factors and their levels studied in the optimization design were useful for tailoring the anticipated formulation characteristics and GLZ release pattern.