Application of Response Surface Methodology Using Face-centered Central Composite Design for Studying Long-Term...

The appropriate design of experiments (DoE) could support post-approval lean-stability approaches. A three-factor three-level face-centered design was constructed to evaluate the long-term stability of gliclazide (GLZ) alginate-gelatin beads. The formulation variables were GLZ%(X₁), alginate:gelatin ratio(X₂), and glutaraldehyde%(X₃). The studied responses included GLZ release at predefined intervals in 0.1 N HCl (2 h) followed by phosphate buffer (pH 7.4). Model-dependent and independent approaches were utilized for comparison. DoE-model validation and reduction were implemented. All the studied formulations showed non-significant changes in the particle size (p > 0.05) and most of them showed similar release profiles before and after storage. The directions of the relationships between the factors' main effects and the responses (Y₁:Q_0.5h, Y₂:Q_2h, and Y₃:Q_4h) remained unchanged after storage. The optimal factor settings based on the proposed optimization criteria were defined. The optimized formulations (OP-1 and OP-2) showed non-significant changes in the particle size after storage. The release profiles and kinetics of OP-1 and OP-2 remained unchanged after storage. No chemical change was indicated (FT-IR). DSC-thermograms of OP-1 indicated GLZ conversion to a more stable polymorph after storage. While OP-2 showed a change in GLZ crystallinity. The stored and fresh beads' surfaces after GLZ release were almost similar. DoE could be utilized to evaluate, optimize, and predict the effects of different formulation variables on the long-term stability of GLZ alginate-gelatin beads.