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 Q_0.5h, Q_2h(pH 1.2) and Q_4h(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 (Q_0.5h and Q_2h). However, in pH 7.4 (Q_4h), 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.