Glimepiride

Current study has developed two precise and direct RP-HPLC approaches for quantitative investigation of glimepiride (GLM) in both mass and pharmaceutical formulations. Glimepiride was analyzed using the RP-HPLC method with C-18 stationary phase and mobile phase of methanol and phosphate buffer (PBS) at pH 4.0 in equivalent volume ratio. The location was established at 239 nm wavelength, and the adaptable stage was extracted at a rate of 0.5 mL/mi. The retention time was observed at 2.470 minutes. Present approach was authenticated in terms of linearity, accurateness, precision, system applicability, limit of detection (LOD), limit of quantification (LOQ), robustness, and ruggedness. It has been demonstrated that the suggested approach is appropriate for monotonous examination of glimepiride in dose and bulk forms, yielding precise results. This method was employed to determine a compound's concentration in commercial pharmaceutical dosage forms. In comparison to alternative chromatographic techniques, this method is more direct, precise, and reproducible, rendering it a superior choice for routine quality control.

The present investigation is to Design and In-vitro evaluation of the sustained release matrix tablets of Glimepiride used for the treatment of type 2 diabetes mellitus. The Glimepiride (6mg) sustained-release (SR) matrix tablets were prepared by wet granulation method using different concentrations of hydrophilic and hydrophobic polymers. Such as Xanthumgum, Microcrystalline Cellulose, Povidone, Guargum, Magnesium Stearate, Pectin. The mechanism of action of glimepiride in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells. The mixture of Glimipride powder was subjected to pre compression evaluation such as angle of repose, loose bulk density, tapped bulk density, hausarner’s ratio and compressibility index. The FTIR Spectrum is carried for the pure drug and for the optimized formula. This indicated that there was not any interaction between drug and polymer. All the formulations (F1-F12) were evaluated for weight variation, hardness, thickness, Friability, Content uniformity and invitro dissolution. The invitro dissolution studies were performed in pH 7.4 indicated that formulation F8 (Glimepiride and Guar gum in the ratio of 1:6) is the most success full formulation of this study and exhibited drug release 99.2% in 12 hr.  To investigate the drug-release kinetics, data were fitted to various kinetic models such as zero-order, first-order, Higuchi equation, Korsmeyer-Pappas equation, and Hixson–Crowell equation.

The poor aqueous solubility of Glimepiride is the major factor limiting its oral bioavailability.  The objective of the work is to enhance the solubility of Glimepiride, there by its bioavailability by using solid dispersion technique. Solid dispersions of Glimepiride were prepared by using Poly vinyl Pyrrolidone (PVP K30), by solvent evaporation method in different ratios of 1:0.5, 1:1, 1:3, 1:5 respectively and evaluated for its in vitro & in vivo release along with Mdsc & FTIR. The equilibrium solubility of solid dispersions was determined in water to study the effect of PVP K30 on solubility of Glimepiride. In Vitro dissolution studies were conducted in water from solid dispersions equivalent to 4 mg of Glimepiride. Protocol bound in vivo studies were conducted in non diabetic rats with the best formulation. Two groups of rats (6 rats in each group) were orally fed Glimepiride as plain drug dispersion (control group) & as drug: PVP K30 solid dispersion (test group). The fall in blood glucose level was monitored over 24 hours. Successful conversion of the crystalline Glimepiride to amorphous solid dispersion was achieved at 1:5 level of drug to PVP K30 (F4). The solid dispersion prepared with PVP K30 at 1:5 level (F4) showed a 4 folds enhancement in aqueous solubility of the drug. So the in vivo studies conducted with 1:5 drug to PVP K30 (F4) solid dispersion, the best formulation, it was observed that the fall in the test group is significantly faster and more intense as compared to the control group. The above study shows that solid dispersion of Glimepiride offers an simple and attractive solution to increase the solubility of the poorly water soluble drug and thereby improve its oral bioavailability. Key words: Glimepiride, Poly vinyl Pyrrolidone (PVP K30), Solid dispersions (SD)

A simple, sensitive, rapid, accurate and precise spectrophotometric method has been developed for estimation of Glimepiride in bulk and tablet dosage forms. The zero order spectra shows maximum absorbance at 249 nm. Calibration graph was found to be linear over the concentration range of 5-30 μg/ml. Results of analysis were validated for precision, range, linearity, interference study and recovery studies, The method can be adopted in its routine analysis.

Drugs belonging to BCS class II, low solubility and high permeability; undergo dissolution-rate limited gastrointestinal absorption. Glimepiride is one of the famous drugs belonging to BCS class II. Its poor aqueous solubility usually causes poor dissolution and unpredicted bioavailability. Hence, formulation techniques that accelerate drug dissolution can guarantee a parallel improvement in bioavailability. Now a days different techniques are available to enhance the solubility of drug like co-solvent, solid dispersion, chemical modification of drug, liquisolid technique etc. One of the favorable strategy to improve the solubility and hence bioavailability of poorly water soluble drugs is theformulation of solid dispersion. The solid dispersion may be prepared by solvent evaporation method, melting method, melt solvent method, kneading method, co-grinding method, co-precipitation method, modified solvent evaporation method, spray drying, gel entrapment techniqueand co-precipitation with supercritical fluid. This review article comprises of the research materialized in the field of solubility and dissolution enhancement of glimepiride.

A simple, rapid, and precise RP-HPLC method for simultaneous analysis of Amlodipine besylate and Glimepiride in bulk and its pharmaceutical formulations has been developed and validated. Amlodipine besylate was separated from Glimepiride by using Grace Smart Altima C8 column (25 cm × 4.6 mm, 5-μm) with a mobile phase consisting of acetonitrile: 20mM phosphate buffer (55:45 (v/v), pH 3.5) a flow rate of 1 mL/min and detection wavelength at 230 nm.  Amlodipine besylate and Glimepiride were eluted with retention times of 5.47 min and 14.17 min respectively. The method was validated for accuracy, precision, linearity, specificity and sensitivity in accordance with ICH (Q2B) guidelines. The results of all the validation parameters were found to be within the acceptable limits. The calibration plots were linear over the concentration ranges from 70-3000ng/mL for Amlodipine besylate and 100-3000ng/mL for glimepiride. The limit of detection and limit of quantification were found to be 19.4ng/mL and 58.8ng/mL for amlodipine besylate, 25.6ng/mL and 76.2ng/mL for glimepiride respectively for both the drugs. From the results it is suggested that the method is simple, reproducible, accurate and precise. The method was successfully applied for the determination of content and the dissolution profile of the combined bilayer tablet dosage form.

Glimepiride loaded polymeric blend matrices were prepared using hydrogel forming polysaccharide like agar, isabgol, aloe vera and gelatin by solution blending method. The polymeric blends were characterized by Fourier-transform infrared spectroscopy revealed that there was no reaction between drug and polymers. The surface morphology of prepared polymeric blends was studied by scanning electron microscopy which suggested that polymeric blend matrices have smooth/rough surface with vacuoles. All the polymeric blend matrices were evaluated for weight variation, hardness, thickness and drug content which suggested that all these parameters were uniform as the total amount of the polymers was fixed to 10%. The polymer blend matrices show good hardness of more than 8 kg/cm2 and drug content more than 95 % suggested that the solution blending method used was suitable for the preparation of polymeric blends. The polymeric blend showed good swelling in the range of 244.12 to 411.22 % within 8 h maintaining integrity of formulation. The in vitro release of the glimepiride was rapid in phosphate buffer pH 6.8 with more than 81.96% released within 8 h. Increases in the amount of agar enhance the in vitro release whereas increases in the amount of gelatin decrease the release of glimepiride. Hence the polymeric blends prepared with agar or gelatins with other polysaccharide as binary or ternary system extend the glimepiride up to 8 h and can be used for effective management of diabetes and also presence of aloe vera may provide synergistic hypoglycemic effect.

Over the years, inclusion complexation of drugs with β-cyclodextrin has emerged as a viable attempt to improve the dissolution of water insoluble drugs. The aim of the present work was to improve the dissolution rate of Glimepiride, by inclusion complexation with β-cyclodextrin. The stoichiometric ratio determined by phase solubility analysis for inclusion complexation of glimepiride with β-cyclodextrin was 1:1, 1:2, & 1:5. The solubility of glimepiride increased with increasing amount of β-cyclodextrin in water. Complexes of glimepiride were prepared with β-cyclodextrin by kneading method and physical mixture. The complexes were characterized by Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) patterns. These studies indicated the inclusion of glimepiride in the cavity of β-cyclodextrin. The complexation resulted in a marked improvement in the solubility of glimepiride. An optimum increase in the dissolution rate of the drug was observed at a drug-polymer concentration of 1:5 concentrations. Mean dissolution time of glimepiride decreased significantly after preparation of complexes of glimepiride with β-cyclodextrin.