Formulation and In-vitro Evaluation of Two Layers Tablet for Dual Release of a Model Drug

Abstract

Objective: Glimepiride is a third-generation sulfonylurea medication that has been used to treat type 2 diabetes (T2D) mellitus. It is class II drug according to the biopharmaceutical classifi cation system (BCS) characterized with its low solubility and high permeability. Due to the drug’s weak water solubility, its bioavailability is restricted by its dissolving rate. This study aimed to develop a bilayer tablet of glimepiride with one layer for immediate release (IR), a dose of 2 mg, a second layer for sustained release (SR), and a 4 mg dose Immediate release layer included solid dispersion of glimepiride . Methods: Glimepiride solid dispersions were prepared utilizing four water-soluble carriers (poloxamer 188, polyethylene glycol (PEG6000), Kollicoat IR and soluplus) by solvent evaporation and fusion techniques at 1:1, 1:2, and 1:4 ratios and evaluated in 0.1 N of HCL buff er pH 1.2 with 1% of sodium lauryl sulphate (SLS) for 2 hours. utilizing a USP-II paddle-type dissolution apparatus containing 900 mL dissolution medium kept at 37 ± 0.5℃ and 50 rpm. The sustained release layer of glimepiride bilayer tablet was prepared using various polymers, including HPMC K15, HPMC K4, xanthan gum, carbopol 934 and ethyl cellulose at 1:1, 1:2,1:3 ratios and combination of polymers in phosphate buff er pH 6.8 for 12 hours. The prepared solid dispersion of immediate release were evaluated by X-ray powder diff raction (PXRD), and fourier transform infrared spectroscopy for selected SD9. The FTIR spectroscopy analysis for selected formula (F24) of sustained layer, angle of repose, Hausner’s ratio and Carr’s Index were used to evaluate the fl owability and compressibility of the formulation powders during the pre-compression investigations, while, thickness, hardness, weight variation, friability, drug content, for prepared tablets. Results: The results revealed that SD9 at ratio (1:4 glimepiride: soluplus) was the optimal formula since 94% of drug released at 2 hours for immediate layer formula 24, which included ethylcellulose polymer in a 1:1 ratio in the sustained layer of the tablet, was chosen as the optimal formula out of another formula (F1–F28), This formula demonstrated acceptable sustained properties of the glimepiride over the course of 12 hours. and approximately 96% of the medication was released. Conclusion: This study succussed in designing bilayer tablets containing glimepiride solid dispersion formulation in the fi rst immediate release layer and untreated pure drug formulation in the second layer for sustaining the release of the drug for a specifi c period of time to be used as the eff ective treatment of type II diabetes mellitus.