Abstract
Glimepiride (GMD) is a third-generation sulfonylurea derivative and one of the top three most-prescribed oral antidiabetic drugs. The need for a depot formulation exists, and a safe and effective antidiabetic therapy is the goal of this study. The aims were to design a depot in situ gel (ISG) formulation and investigate the main factors that control the initial burst and sustain the GMD effect using the Box-Behnken design. The studied factors were polymer percent (X1), plasticizer percent (X2) and benzyl benzoate percent in N-methyl-2-pyrrolidone (X3). The results revealed that X2 is the only factor that showed significant effects on all investigated responses. Scanning electron microscopy images showed that an increase in PEG % improved the smoothness and reduced the porosity of the ISG formulation surface. The GMD plasma levels in diabetic rats revealed no significant difference (p < 0.05) between the maximum GMD plasma concentrations of the optimized GMD-ISG formula (10 mg/ kg) and oral marketed GMD tablets (1 mg/kg). This result ensures that the optimized formula does not exceed the maximum safe plasma concentration. In addition, the optimized GMD-ISG formulation showed a depot effect that lasted for 14 days post-injection. This approach to controlling GMD release using an in situ forming system could be useful for improving patient compliance and diabetes treatment effectiveness.
Highlights
The antidiabetic drug glimepiride (GMD) is classified as a third-generation sulfonylurea derivative used in the treatment of non-dependent type II diabetes
The goal was to sustain the release of GMD from the in situ gel (ISG) formulation by controlling its initial burst from the designed formula
scanning electron microscopy (SEM) photographs (Fig. 1) revealed that an increase in the percentage of polyethylene glycol (PEG) improved the smoothness and reduced the porosity of the prepared ISG formulation surfaces. These changes in the formulation surface characteristics lead to a reduction in the surface area exposed to the dissolution media, which subsequently reduces the initial burst effect of GMD release
Summary
The antidiabetic drug glimepiride (GMD) is classified as a third-generation sulfonylurea derivative used in the treatment of non-dependent type II diabetes. The goal was to sustain the release of GMD from the ISG formulation by controlling its initial burst from the designed formula. The mathematical design was applied to investigate, optimize, and explore the main interactions and quadratic effects of the selected factors on the initial burst after 2 and 24 h and the cumulative amount of GMD released after 28 days from the ISG formulations.
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