الفهرس 
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Abstract
Background: Glimepiride is an anti-diabetic and third-generation sulfonylurea drug belonging to class II BCS (Biopharmaceutical Classification System), is characterized by its low solubility and high permeability. Aim: Improve the solubility of glimepiride by complexation and then formulating it into Rapid orally disintegrating tablets (RODTs), resulting in fast release and rapid dissolution of the drug, hence improving absorption and bioavailability. Materials and Methods: The complexes of glimepiride were prepared with different types of polymers [mannitol, beta-cyclodextrin (β-CD), and hydroxyl propyl beta-cyclodextrin (HP-β-CD)] using two methods (Kneading and spray drying (spr-dry); all formulations were prepared to measure drug content. A statistical 32 full factorial design model was applied to assess the effect of Microcrystalline cellulose (MCC) level (X1) and partially pre gelatinized starch (PPGS) level (X2). All formulations were prepared to measure friability, tablet hardness, and disintegration time. Results: from the D optimal design, the best preparation method of complexation was the spray drying method with drug content (C2:95%, higher desirability). Then, the optimal complex C2 was characterized by Fourier transform infrared (FT-IR), Differential scanning calorimetry (DSC), and Scanning electron microscope (SEM). Showed that the manufactured RODTs were compiled with the USP requirements. In addition, ANOVA analysis demonstrated that PPGS level and MCC level had a significant effect (P<0.0001) on the dependent responses. Numerical optimization using the desirability approach was also applied to optimize the independent variables. Formula (G13) found that higher desirability (0.953) could be achieved for PPGS (60 %) and MCC (15 %). In the rat model, the pharmacodynamics studies for G13 showed that the percentage decrease in blood glucose level 40.15% ± 2.64 at 30 min was significantly lower (P ≤ 0.05) when compared to pure Glimepiride and Amaryl. Conclusion: RODTS tablets of G13 were successfully prepared with improved solubility and bioavailability.
Keywords: Factorial design; Glimepiride; RODTS; Complexation; Super-disintegrant; Direct compression; In vivo study.