Controlled release of Glibenclamide (cas 10238-21-8) from monolithic silica subdermal implants produced by the sol-gel process and its use for hyperglycaemia treatment in a murine model
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Add time:07/30/2019 Source:sciencedirect.com
Glibenclamide (cas 10238-21-8) is an anti-hyperglycaemic drug that is commonly used for the treatment of type 2 diabetes mellitus and has promising new medical indications. However, this drug is associated with high rates of serious hypoglycaemic episodes as a result of its pharmacological activity. Administering the drug through controlled release delivery systems could reduce the incidence of these episodes. In this study, glibenclamide silica monolithic xerogel implants for subdermal application (GMSIx) were developed using the sol-gel technique for matrix synthesis with TEOS with different drying conditions (environmental, 60, 90, and 120 °C, which were named as GMSIE, GMSI60, GMSI90, and GMSI120, respectively). The inclusion of the drug in monoliths was monitored by DSC, FTIR, and PXRD. The effect of drying conditions on the morphology, moisture content, hardness, dosage uniformity, surface characteristics, and drug release mechanism of glibenclamide from the matrices was systematically investigated. Oral Glucose Tolerance Tests were performed with mice to evaluate the efficacy of the GMSI in maintaining blood glucose levels. Glibenclamide was completely included in a non-crystalline solid form in the matrixes. The moisture content, hardness, dosage uniformity, and surface characteristics depend on the drying conditions. The monolithic matrices showed a mesoporous surface with high surface area, and a narrower pore size distribution occurred for GMSI60. GMSIE and GMSI60 showed non-Fickian anomalous Korsmeyer-Peppas glibenclamide release kinetics. GMSI90 and GMSI120 showed controlled release of the drug through dissolution. When GMSI60 was administered to mice, glucose blood levels were effectively maintained despite a high oral glucose load in the animals, showing a sustained effect of the drug released from this new sol-gel drug delivery system.
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