Solubility Of Glibenclamide Research Articles

Solubility of glibenclamide in carbitol and 1-propanol mixtures at different temperatures

ABSTRACT In this work, the solubility of glibenclamide in the non-aqueous mixtures of carbitol and 1-propanol was studied at temperatures ranging from 293.2 K to 313.2 K using a shake-flask technique. The findings were represented by five computational models, including the van’t Hoff, the Jouyban-Acree, the Jouyban-Acree-van’t Hoff, the mixture response surface and the modified Wilson models. These models showed strong correlation and prediction capabilities, as indicated by the mean relative deviations for the back-calculated data. Furthermore, the thermodynamic analysis was conducted for solubility data using van’t Hoff and Gibbs equations.

Correlation of Solubility Thermodynamics of Glibenclamide with Recrystallization and In Vitro Release Profile.

The solubility of glibenclamide was evaluated in DMSO, NMP, 1,4-dioxane, PEG 400, Transcutol® HP, water, and aqueous mixtures (T = 293.15~323.15 K). It was then recrystallized to solvate and compressed into tablets, of which 30-day stability and dissolution was studied. It had a higher solubility in 1,4-dioxane, DMSO, NMP (Xexp = 2.30 × 103, 3.08 × 104, 2.90 × 104) at 323.15 K, its mixture (Xexp = 1.93 × 103, 1.89 × 104, 1.58 × 104) at 298.15 K, and 1,4-dioxane (w) + water (1−w) mixture ratio of w = 0.8 (Xexp = 3.74 × 103) at 323.15 K. Modified Apelblat (RMSD ≤ 0.519) and CNIBS/R-K model (RMSD ≤ 0.358) suggested good comparability with the experimental solubility. The minimum value of ΔG° vs ΔH° at 0.70 < x2 < 0.80 suggested higher solubility at that molar concentration. Based on the solubility, it was recrystallized into the solvate, which was granulated and compressed into tablets. Among the studied solvates, the tablets of glibenclamide dioxane solvate had a higher initial (95.51%) and 30-day (93.74%) dissolution compared to glibenclamide reference (28.93%). There was no stability issue even after granulation, drying, or at pH 7.4. Thus, glibenclamide dioxane solvate could be an alternative form to improve the molecule’s properties.

Comparison In-vitro Release and pH Effect Among Different Oral Antidiabetic Drugs: Review Article

Diabetes is a metabolic condition that affects how the body utilizes digested food for growth and energy. The majority of the food we consume is broken down into glucose, which is the form of sugar in our blood. Glucose is the body's primary fuel source. The solubility of glibenclamide (glibenclamide), metformin, and sitagliptin were evaluated in triplicate in different pH using a water bath shaker at 37oC using the shake-flask technique. The quantity of medicine accessible for absorption is determined by the drug release. Each drug's physiochemical characteristics substantially impact release along the G.I.T. For each medication, a calibration curve and solubility measurement were performed. In the duodenum and the small intestine, glibenclamide was released more efficiently and fast than metformin and sitagliptin, which had higher pKa values than glibenclamide, i.e., the metformin and sitagliptin were released more quickly and efficiently in pH 1.2 and pH 5.8. Glibenclamide is absorbed from the stomach, if not completely.

Formulation and Characterization of Glibenclamide Solid Lipid Submicroparticles Formated by Virgin Coconut Oil and Solid Matrix Surfactant

Glibenclamide has the biopharmaceutics classification system (BCS) class II which has high permeability and low solubility. The solubility of glibenclamide can be enhanced by forming solid lipid nanoparticles (SLN). This research has the aim to prepare and characterize SLN loading glibenclamide. The glibenclamide SLN formula was composed by using the liquid lipid as virgin coconut oil (VCO), PEG 6000 as a solid matrix, tween 80 with various concentrations as a stabilizer, and PEG 400 as co-surfactant. Characterization was conducted by determining the encapsulation efficiency (%EE), size measurement, particle size distribution, and zeta potential of SLN glibenclamide. SLN formation was also tested for its physical stability based on the heating-cooling cycle method. The optimum formula was obtained at the concentration of tween-80 of 1 mg/mL yielding the %EE value of 60.6194%, and pH 6.01. The results of particles diameter analysis were 175.5 ± 10.07 nm with a polydispersity index (PDI) of 0.1270, and zeta potential of +5.9 mV respectively. Stability testing by the heating-cooling cycle method has shown the instability of the SLN glibenclamide form under extreme temperatures and mechanics. It could be concluded that the results of characterization of glibenclamide SLN showed appropriate physical properties for nanoparticulate formulation.

SOLUBILITY ENHANCEMENT OF GLIBENCLAMIDE USING MESOPOROUS SILICA

Glibenclamide is a BCS Class II drug and poses a major problem during formulation development. In the present study, adsorption onto various carriers was used to enhance the solubility of glibenclamide. It was observed that solubility of glibenclamide was greatly enhanced by adsorbing onto mesoporous silica. The increase in solubility of poorly soluble drugs is often associated with the generation of supersaturation, which results in the risk of drug precipitation. HPMC E5 was used as precipitation inhibitor to maintain sink condition for a longer duration. A 32 full factorial design was adopted to optimize the ratio of glibenclamide (X1) and mesoporous silica as a carrier (X2) and the effect of different ratios was studied on percent yield, percent drug loading, and percent drug release. X-ray powder diffraction (XRPD) and Differential scanning calorimetry studies were performed to investigate any possible interaction in between glibenclamide and mesoporous silica. An optimum batch of drug adsorbate was used to prepare immediate-release tablets. The tablets prepared were evaluated for thickness, uniformity of weight, hardness, friability, in-vitro disintegration time, and in vitro drug release study.

Solubility Determination and Correlation of Glibenclamide in 11 Monosolvents and (Acetone + Acetonitrile) Binary Solvents from 283.15 K to 323.15 K

Glibenclamide (GCM) is an oral antihyperglycemic drug and widely used to treat type-II diabetes. The quality of the GCM product impacts the efficacy of the medicine. However, the quality of the product is determined by the crystallization process, in which the solubility property plays a significant role. In this study, GCM solubility in 11 monosolvents (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, acetone, acetonitrile, methyl isobutyl ketone, methyl acetate and ethyl acetate) and (acetone + acetonitrile) binary solvents, has been determined through a gravimetric method from 283.15 K to 323.15 K. It elucidates that GCM has the highest solubility in acetone among the 11 monsolvents. Meanwhile, the solubility of GCM in (acetone + acetonitrile) binary solvents increases when the mole fraction of acetone rises. Then, we correlated the solubility data in monosolvents using the modified Apelblat model and nonrandom two-liquid (NRTL) model. Besides, the modified Apelblat model, the CNIBS/R-K...

FORMULATION OF IMMEDIATE RELEASE (IR) ATORVASTATIN CALCIUM PELLETS AND SUSTAINED RELEASE (SR) GLIBENCLAMIDE FOR FIXED-DOSE COMBINATION DOSAGE FORM

Objective: The objective of the present research was to develop fixed-dose combinations for the treatment of dyslipidemia, associated with type-II diabetes mellitus for improvement of glucose tolerance.Methods: Multiple unit pellet systems (MUPSs) consisting immediate release atorvastatin calcium pellets and sustained release glibenclamide were formulated by spheronization technique. The characterization of formulated pellets was done by Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC) studies, and formulated pellets were evaluated for solubility, viscosity, pH, and in vitro studies.Results: From FT-IR and DSC studies, it was confirmed that no chemical interaction existed between the drug and the natural polymers used. Solubility of glibenclamide was found to be 4.38 and 18.24 and atorvastatin calcium was found to be 6.84, 214.67, and 287.43 g/L. The viscosity of 1% w/v of locust bean gum, guar gum, and ghatti gum was found to be 169 cP, 124 cP, and 31 cP in distilled water. The pH of locust bean gum, guar gum, and gum ghatti solutions was found to be 5.6±0.49, 5.2±0.27, and 4.7±0.51. The in vitro studies suggested that glibenclamide pellets had shown a sustained release till 12 h, while atorvastatin calcium had shown immediate release of drug due to rapid disintegration of pellets.Conclusion: Thus, MUPS can be considered as an alternative approach to treat diabetes induced dyslipidemia.

Solubility enhancement of glibenclamide in choline–tryptophan ionic liquid: Preparation, characterization and mechanism of solubilization

A new ionic liquid solvent was prepared from choline as a cation and tryptophan as the anion. The produced ionic liquid was characterized by NMR, UV and HPLC. The obtained solvent was shown to form in a ratio of 1:1 (choline: tryptophan). The produced solvent was shown to increase the solubility of the low water solubility drug glibenclamide. The mechanism of the observed solubility enhancing effect of the drug was investigated and it did not seem to be simply due to increase in the pH of the medium. The most likely mechanism of increase in the solubility of glibenclamide (Glib) is the formation of complex hydrogen bonds and π–π interaction of the aromatic rings.

Enhancement of Dissolution Properties of Glibenclamide by using Liquisolid Compact Technique

Glibenclamide, a sulfonylurea derivative is widely used as hypoglycaemic agent. Glibenclamide is a highly permeable class II drug. Hence, rate of oral absorption is often controlled by the dissolution rate in the gastrointestinal(GI)tract. Therefore, the Liquisolid compact of Glibenclamide has been prepared for the enhancement of dissolution of Glibenclamide. Neusilin US2 was selected as carrier material and Aerosil 200 was selected as coating material. A Central composite factorial design was applied to optimize the drug release profile systematically. The amounts of drug (%) in PEG 400 (X1) and Excipient ratio, R (X2) were selected as independent variables. Angle of repose (Y1), Hardness (Y2) and CPR at 10 min (Y3) were selected as dependent variables. All the batches of Liquisolid compacts showed significance improvement in dissolution of Glibenclamide. Various dissolution parameters like DP10min, %DE10min and MDT of optimized batch and direct conventional tablet were compared. DSC and XRD analysis of pure Glibenclamide, physical mixture and final formulation indicated that the drug was solubilized in non-volatile vehicle and solubilization of Glibenclamide was the main cause of enhancement of solubility of Glibenclamide. Storage of the prepared formulations at 45°C for one month showed no any chemical incompatibility. It was concluded that, Liquisolid compact technique can be a simple and effective to enhance the dissolution of poorly water soluble drug.

Solution thermodynamics and solubility prediction of glibenclamide in Transcutol + water co-solvent mixtures at 298.15–333.15 K

Solution thermodynamics and solubility of glibenclamide (GBN) in binary co-solvent mixtures of Transcutol + water at temperature range of 298.15-333.15 K were investigated in present study. The modified Apelblat model was used to predict the solubility of GBN in co-solvent mixtures at various temperatures. The highest and lowest solubility of GBN were observed in pure Transcutol and pure water, respectively. Moreover, all co-solvent mixtures had highest solubility at 333.15 K. The experimental solubility data of GBN was correlated well with the modified Apelblat model at each temperature studied with relative absolute deviation in the range of 0.008-5.903 %. The correlation coefficients in co-solvent mixtures were observed in the range of 0.995-0.999 which indicated good fitting of experimental data with calculated one. The enthalpies and entropies for GBN dissolution were observed in the range of 2.012-38.215 kJ mol(-1) and 6.748-114.709 J mol(-1) K(-1), respectively indicating its dissolution is endothermic and an entropy-driven process. These results indicated that Transcutol can be used as a co-solvent in preformulation studies and formulation development of GBN.

Thermodynamics-based mathematical model for solubility prediction of glibenclamide in ethanol–water mixtures

Temperature-dependent solubility data of glibenclamide (GBN) in various ethanol–water mixtures is not reported in literature so far. Therefore, the aim of this study was to determine the mole fraction solubility of GBN in various ethanol–water mixtures at the temperature range of 293.15 to 318.15 K. The solubility of GBN was determined by reported shake flask method and the experimental data was fitted in thermodynamics-based modified Apelblat model. The solubility of GBN was found to be increased with increase in temperature and mass fraction of ethanol in ethanol–water mixtures. The experimental data of GBN was well correlated with the modified Apelblat model at each temperature range with correlation coefficient of 0.9940–1.0000. The relative absolute deviation (AD) was found to be less than 0.1% except in pure ethanol and water. The positive values of enthalpies and entropies for GBN dissolution indicated that its dissolution is endothermic and an entropy-driven process.

Glibenclamide-loaded self-nanoemulsifying drug delivery system: development and characterization

Objective: To develop and characterize self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble drug, glibenclamide (GBD). Methods: Solubility of GBD was determined in various vehicles. Phase diagrams were constructed to identify efficient self-emulsification region using oils, surfactants, and cosurfactants in aqueous environment. Formulations were assessed for drug content, spectroscopic clarity, emulsification time, contact angle, zeta potential, particle size, and dissolution studies. On the basis of similarity and dissimilarity of particle size distribution, formulations were further characterized using principal component analysis and agglomerative hierarchy cluster analysis. Results: Among the formulations prepared and evaluated, optimized formulation showed mean particle size between 15.65 and 32.70 nm after 24 hour postdilution in various media. Dilution volume had no significant effect on particle size. Transmission electron microscopy of these formulations confirmed the spherical shape of globules with no signs of coalescence of globules and precipitation of drug. The relevance of difference in t50% and percent dissolution efficiency were evaluated statistically by two-way ANOVA. Infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction studies indicated compatibility between drug, oil, and surfactants. Conclusions: The results of this study indicate that the self-nanoemulsifying drug delivery system of GBD, owing to nanosize, has potential to enhance its absorption and without interaction or incompatibility between the ingredients.

Improvement in Solubility of Poorly Water Soluble Drug by Cogrinding with Highly Branched Cyclic Dextrin

We investigated the enhancement of the solubility of glibenclamide (GCM), a poorly water soluble anti-diabetes drug, by cogrinding it with highly branched cyclic dextrin (HBCD) using a ball mill. Highly branched cyclic dextrin (HBCD) is a novel cyclic glucan produced from waxy corn starch by the cyclization reaction of a branching enzyme. When GCM crystals were coground with HBCD for 2 h, the solubility of GCM was improved to 12.4 μg/ml, while the concentration of HBCD was 5.0 mg/ml. Additionally, the GCM solubilized with HBCD was chemically stable in aqueous solution for at least 1 week at room temperature. The peak intensity assigned to crystalline GCM disappeared after cogrinding it by observing its powder X-ray diffraction pattern, which means that the crystalline structure of GCM could be disrupted. In the DSC measurement, the ground mixture showed a single endothermic peak, even though a temperature depression of the endothermic peak due to GCM crystal was observed. After the cogrinding, two sharp peaks assigned to sulfonylurea and benzoyl carbonyl stretching bands varied to broaden the peak to around 1640 cm−1 in the C=O stretching region. These results suggested the formation of solid dispersion between GCM and HBCD.

Enhancing effect of switching iontophoresis on transdermal absorption of glibenclamide

Glibenclamide(GLI) is widely used as an oral hypoglycemic drug in the treatment of non-insulin dependent diabetes mellitus (NIDDM). We investigated The enhancing effect of switching iontophoresis on the transdermal absorption and reduction of skin irritation to develop a transdermal dosage form of GLI. The 0.1% of Gli suspensions in 0.2 M tris-HCl buffer of pH 7.4, 8.0 and 8.5 were prepared as donor solutions. We examined drug permeation through the excised rat abdominal skin, drug absorption in rats and reduction of skin irritation after application of switching iontophoresis for 1 h using DC 10 V. The solubility of GLI in 0.2 M tris-HCl buffer increased with a rise in pH. In the permeation study, GLI was permeated continuously and the cumulative amount of permeated GLI increased using an alkaline donor solution. In the drug absorption study, the application group of pH 8.5 gave higher plasma concentration levels than those of pH 7.4 and 8.0 groups. The skin irritation evoked by the application of iontophoresis was pathologically studied. A total irritation score (TIS) was estimated as a judging standard for the skin damage. The TIS value increased dependently with a rise in pH. However, it was considered that the skin irritations were not serious and small matters. The results demonstrate the possibility of iontophoretic transdermal administration of GLI and the effect of drug solubility in the donor solution on the absorption of GLI.

Co-administration of a water-soluble polymer increases the usefulness of cyclodextrins in solid oral dosage forms.

The aim of this study was to investigate the effect of cyclodextrins (beta-CD, HP-beta-CD and (SBE)7m-beta-CD), and co-administration of a water-soluble polymer (HPMC) and cyclodextrins, on the oral bioavailability of glibenclamide in dogs. Effects of cyclodextrins on the aqueous solubility of glibenclamide, with and without hydroxypropylmethylcellulose (HPMC), were determined by a phase-solubility method. Solid inclusion complexes were prepared by freeze-drying. Glibenclamide was administered orally and intravenously to beagle dogs. Aqueous solubility of glibenclamide increased as a function of cyclodextrin concentration, showing an AL-type diagram for beta-CD and an Ap-type diagrams for both of the beta-CD derivatives studied. HPMC enhanced the solubilising effect of cyclodextrins, but did not affect the type of phase-solubility diagram. Orally administered glibenclamide and its physical mixture with HP-beta-CD showed poor absolute bioavailability, while orally administered glibenclamide/cyclodextrin-complexes significantly enhanced the absolute bioavailability of glibenclamide. Orally administered glibenclamide/beta-CD/HPMC and glibenclamide/(SBE)7m-beta-CD/HPMC complexes showed similar absolute bioavailability compared to formulations not containing HPMC, even though 80% (in the case of (SBE)7m-beta-CD) or 40% (in the case of beta-CD) less cyclodextrin was used. The oral bioavailability of glibenclamide was significantly increased by cyclodextrin complexation. HPMC increased the solubilising effect of cyclodextrins and, therefore, the amount of cyclodextrin needed in the solid dosage form was significantly reduced by their co-administration. In conclusion, the pharmaceutical usefulness of cyclodextrins in oral administration may be substantially improved by co-administration of a water-soluble polymer.