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

The aim of this study was to optimize the formulation of alginate-gelatin (AL-GL) beads containing gliclazide (GLZ) employing design of experiments (DOE). DOE enabled identification of the interaction between the studied factors, deep understanding of GLZ release pattern and acceleration of the optimization process. A three-factor, three-level face centered design was employed. The effects of GLZ content (GLZ%, X), polymer ratio (AL:GL ratio, X), crosslinker concentration (glutaraldehyde, GA%, X), 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. Increasing GA% (X) decreased IE (Y) with the highest magnitude of effect among the studied factors. On the other hand, increasing alginate content in AL:GL ratio (X) increased IE (Y). The amount of GLZ released Q, Q(pH 1.2) and Q(pH 7.4) decreased by increasing GLZ% (X) and AL:GL ratio (X). 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% (X) and GLZ release in pH 1.2 (Q and Q). However, in pH 7.4 (Q), 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. The selected factors and their levels studied in the optimization design were useful for tailoring the anticipated formulation characteristics and GLZ release pattern.