Second-generation Sulfonylurea Research Articles

Anthelminthic activity of glibenclamide on secondary cystic echinococcosis in mice.

Cystic echinococcosis (CE) is a worldwide parasitic zoonosis caused by the larval stage of Echinococcus granulosus. Current chemotherapy against this disease is based on the administration of benzimidazoles (BZMs). However, BZM treatment has a low cure rate and causes several side effects. Therefore, new treatment options are needed. The antidiabetic drug glibenclamide (Glb) is a second-generation sulfonylurea receptor inhibitor that has been shown to be active against protozoan parasites. Hence, we assessed the in vitro and in vivo pharmacological effects of Glb against the larval stage of E. granulosus. The in vitro activity was concentration dependent on both protoscoleces and metacestodes. Moreover, Glb combined with the minimum effective concentration of albendazole sulfoxide (ABZSO) was demonstrated to have a greater effect on metacestodes in comparison with each drug alone. Likewise, there was a reduction in the cyst weight after oral administration of Glb to infected mice (5 mg/kg of body weight administered daily for a period of 8 weeks). However, in contrast to in vitro assays, no differences in effectiveness were found between Glb + albendazole (ABZ) combined treatment and Glb monotherapy. Our results also revealed mitochondrial membrane depolarization and an increase in intracellular Ca2+ levels in Glb-treated protoscoleces. In addition, the intracystic drug accumulation and our bioinformatic analysis using the available E. granulosus genome suggest the presence of genes encoding sulfonylurea transporters in the parasite. Our data clearly demonstrated an anti-echinococcal effect of Glb on E. granulosus larval stage. Further studies are needed in order to thoroughly investigate the mechanism involved in the therapeutic response of the parasite to this sulfonylurea.

Study of gliquidone degradation behavior by high-performance thin-layer chromatography and ultra-performance liquid chromatography methods.

Gliquidone (GQ) is an oral hypoglycemic agent, belonging to second-generation sulfonylurea derivatives. New high-performance thin-layer chromatography (HPTLC) and ultra-performance liquid chromatography (UPLC) methods have been developed and validated and used for complete stability study of GQ following International Conference on Harmonization guidelines. GQ was subjected to stress and forced degradation under hydrolytic, oxidative and photolytic conditions. The drug was found to be unstable under acidic, alkaline and oxidative conditions with the formation of gliquidone sulfonamide (GQS), while a marked stability was confirmed under thermal and photolytic stress conditions. GQS is the British pharmacopeial impurity A of GQ and also considered as its synthesis intermediate. The developed chromatographic methods have been utilized for anticipating the degradation behavior of GQ under the studied conditions and then used for quantitation of GQ and GQS either in their pure forms or in laboratory prepared mixtures. The methods were successfully applied to GQ in pharmaceutical formulation. The methods have the advantages of being sensitive and less time consuming compared with the reported methods. The obtained results were statistically compared with a reported HPLC method showing no significant difference regarding both accuracy and precision.

Development of a Sustained Release Solid Dosage Formulation for Delivery of a Poorly Water Soluble Hypoglycemic Agent Using Novel Ceramic Vehicle

Gliclazide is a second-generation sulfonylurea compound used as a prescription medicine in the treatment of non insulin dependent diabetes mellitus (NIDDM) or type II diabetes. As a consequence of the poor aqueous solubility, the therapeutic efficacy of the drug in oral dosage form suffers from major drawbacks, e.g., inter-individual variable bioavailability. To overcome the same, various extended/sustained release (SR, matrix mediated) oral dosage formulations have been attempted and in the present communication, we report the use of a biocompatible and biodegradable anionic clay, known as Mg–Al layered double hydroxides (LDHs) to encapsulate the gliclazide drug by ex situ anion exchange process, to form LDH-GLZSR sustained release tablet, known as LDH-GLZSR. It was characterized structurally and compositionally by various analytical techniques. The LDH-GLZSR tablet was manufactured by direct compression method, followed by using microcrystalline cellulose as binder, crospovidone as disintegrator and magnesium stearate as lubricant. Different post formulation parameters of LDH-GLZSR tablets were evaluated and in vitro dissolution study was carried out in two pH conditions (1.2 for stomach and 6.8 for colon), comparing the same to a market available polymer based SR formulation (tablet) of the same drug, named as GLZ-SR to estimate the suitability of the former for a similar use.

Design and Development of Fast Dissolving Tablet of Gliclazide

In the present study, Gliclazide is a second-generation sulfonyl urea derivative used to treat non-insulin dependent diabetes mellitus. The drug has been classified as class-II drug according to biopharmaceutical classification system having low solubility and high permeability. So, an attempt was made to enhance the solubility of gliclazide by solvent evaporation technique. A significant enhancement of gliclazide dissolution rate will be obtained using by using suitable techniques. In this PVP-k30, polyethylene glycol and soluplus were mixed with the drug in different ratios (1:1, 1:3) and prepare P1, P2, PE1, PE2, S1 and S2 solid dispersion batches. The optimized solid dispersions P1 were further kneaded with suitable proportions of super disintegrants such as; Cross carmellose and Sodium starch glycolate. Dissolution profile will show decrease amount of drug release at specified time. DSC as well as X-ray diffraction showed reduced drug crystallinity in SDs. Scanning electron microscopy and particle size analysis revealed significant decreased particle size of the drug in SDs. FT-IR spectroscopy demonstrated no detectable interactions between the drug and excipients. On that the P1 batch will be consider for eight different fast dissolving tablets Preparation. The prepared FDT’s were evaluated for various parameters like disintegration time, wetting time, drug content, in vitro drug release study etc. and shows the satisfactory result. The formulation of F-4 containing cross carmellose sodium (5%) showed better result in disintegration time 11 sec. and maximum in vitro drug release of 99.89% at the end of 40 minutes.

Short-Term High-Fat Diet (HFD) Induced Anxiety-Like Behaviors and Cognitive Impairment Are Improved with Treatment by Glyburide.

Obesity-associated comorbidities such as cognitive impairment and anxiety are increasing public health burdens that have gained prevalence in children. To better understand the impact of childhood obesity on brain function, mice were fed with a high-fat diet (HFD) from weaning for 1, 3 or 6 weeks. When compared to low-fat diet (LFD)-fed mice (LFD-mice), HFD-fed mice (HFD-mice) had impaired novel object recognition (NOR) after 1 week. After 3 weeks, HFD-mice had impaired NOR and object location recognition (OLR). Additionally, these mice displayed anxiety-like behavior by measure of both the open-field and elevated zero maze (EZM) testing. At 6 weeks, HFD-mice were comparable to LFD-mice in NOR, open-field and EZM performance but they remained impaired during OLR testing. Glyburide, a second-generation sulfonylurea for the treatment of type 2 diabetes, was chosen as a countermeasure based on previous data exhibiting its potential as an anxiolytic. Interestingly, a single dose of glyburide corrected deficiencies in NOR and mitigated anxiety-like behaviors in mice fed with HFD-diet for 3-weeks. Taken together these results indicate that a HFD negatively impacts a subset of hippocampal-independent behaviors relatively rapidly, but such behaviors normalize with age. In contrast, impairment of hippocampal-sensitive memory takes longer to develop but persists. Since single-dose glyburide restores brain function in 3-week-old HFD-mice, drugs that block ATP-sensitive K+ (KATP) channels may be of clinical relevance in the treatment of obesity-associated childhood cognitive issues and psychopathologies.

Glycemia control and glucose-lowering therapy in patients with type 2 diabetes mellitus and cardiovascular disease (review of multicenter randomized trials)

The use of modern pharmaceuticals and cardiovascular disease (CVD) treatment methods has increased life expectancy and improved the quality of life of both patients with normal carbohydrate metabolism and diabetes mellitus (DM). This study provides a review of the literature on glycaemic control and choice of glucose-lowering therapy in patients with type 2 DM (T2DM) and CVD. According to the latest recommendations for the prevention of CVD, the target level of glycated haemoglobin (HbA1c) should be less than 7.0% and 7.5%–8.0% in older patients to decrease the risk of hypoglycaemia. The target blood glucose level is 7.7–10 mmol/L. The results of randomized clinical trials (RCTs) revealed that the adverse effects of second-generation sulfonylureas include critical hypoglycaemia episodes and increases in CVD-associated complications and mortality. Metformin reduces the risk of CVD in comparison with second-generation sulfonylurea derivates and insulin. Thiazolidinediones are not currently used for patients with CVD, and the safety of GLP-1 analogues and SGLT-2 inhibitors is still under investigation. When metformin therapy is ineffective, DPP-4 inhibitors should be prescribed and renal function should be monitored. Metformin is contra-indicated in patients with severe chronic heart failure (CHF) and acute myocardial infarction (AMI) because of the risk of lactic acidosis with tissue hypoxia. Thus, insulin is the drug of choice for glycaemic control in CVD patients with chronic kidney disease, severe heart failure or other acute clinical conditions.

Development and Evaluation of Polymer-bound Glibenclamide Oral Thin Film

Glibenclamide (GLB) is a second-generation sulfonylurea oral hypoglycemic agent used in the treatment of non-insulin dependent diabetes mellitus. The use of this drug is limited due to its poor dissolution and pharmacokinetic profile. In order to nullify these drawbacks, GLB oral thin films were prepared and evaluated to study the influence of preparatory conditions on the physicochemical properties by using Scanning Electron Microscopy (SEM), Fourier Transform Infra-red Spectroscopy (FTIR) and Differential Scanning Calorimetric (DSC). The surface pH of the GLB thin film was found to be in the range of 6.50 ± 0.10 and it is non-irritant to mucosal lining of the oral cavity. The results of the SEM analysis showed uniform surface morphology with homogenous distribution of GLB pure drug in PVP matrix. The in vitro drug release profile at pH 5.0 and 7.5 revealed sustained release patterns for a period of 8 h. The GLB oral thin film showed an enhanced in vivo insulin release profiles as compared to pure GLB drug. Thus, the results of the present study revealed that, the prepared GLB oral thin film can be used as alternative strategy to deliver glibenclamide for diabetes mellitus as it showed a significant role in increasing in vitro dissolution and in vivo insulin release profiles.

Analysis of glipizide binding to normal and glycated human serum albumin by high-performance affinity chromatography.

In diabetes, the elevated levels of glucose in the bloodstream can result in the nonenzymatic glycation of proteins such as human serum albumin (HSA). This type of modification has been shown to affect the interactions of some drugs with HSA, including several sulfonylurea drugs that are used to treat type II diabetes. This study used high-performance affinity chromatography (HPAC) to examine the interactions of glipizide (i.e., a second-generation sulfonylurea drug) with normal HSA or HSA that contained various levels of in vitro glycation. Frontal analysis indicated that glipizide was interacting with both normal and glycated HSA through two general groups of sites: a set of relatively strong interactions and a set of weaker interactions with average association equilibrium constants at pH 7.4 and 37 °C in the range of 2.4-6.0 × 10(5) and 1.7-3.7 × 10(4) M(-1), respectively. Zonal elution competition studies revealed that glipizide was interacting at both Sudlow sites I and II, which were estimated to have affinities of 3.2-3.9 × 10(5) and 1.1-1.4 × 10(4) M(-1). Allosteric effects were also noted to occur for this drug between the tamoxifen site and the binding of R-warfarin at Sudlow site I. Up to an 18% decrease in the affinity for glipizide was observed at Sudlow site I ongoing from normal HSA to glycated HSA, while up to a 27% increase was noted at Sudlow site II. This information should be useful in indicating how HPAC can be used to investigate other drugs that have complex interactions with proteins. These results should also be valuable in providing a better understanding of how glycation may affect drug-protein interactions and the serum transport of drugs such as glipizide during diabetes.

Synthesis and blood glucose and lipid-lowering effects of benzothiazole-substituted benzenesulfonylurea derivatives

Sulfonylurea drugs are widely used for the therapy of non-insulin-dependent diabetes mellitus. These drugs improve glucose and lipid levels by stimulating insulin secretion by the pancreatic β-cell comprising two generations with the second one more potent than the first. Glibenclamide is a well-known and potent second-generation sulfonylurea oral hypoglycemic drug which is most widely used in type II diabetes. In this research, five new analogs were synthesized by exchanging the lipophilic phenyl and urea moieties in the first and the end of the molecule with chlorobenzamide and hydrophilic and antidiabetic aminobenzothiazole substituents. Their glucose and lipid-lowering activities were evaluated and compared to the standard drug. Results showed that all of the new compounds exhibited better activities. In addition, in particular aminomethylbenzothiazoles derivatives could have exerted prominent hypoglycemic and a noticeable hypolipidemic effects superior to glibenclamide.

Glipizide suppresses embryonic vasculogenesis and angiogenesis through targeting natriuretic peptide receptor A

Glipizide, a second-generation sulfonylurea, has been widely used for the treatment of type 2 diabetes. However, it is controversial whether or not glipizide would affect angiogenesis or vasculogenesis. In the present study, we used early chick embryo model to investigate the effect of glipizide on angiogenesis and vasculogenesis, which are the two major processes for embryonic vasculature formation as well as tumor neovascularization. We found that Glipizide suppressed both angiogenesis in yolk-sac membrane (YSM) and blood island formation during developmental vasculogenesis. Glipizide did not affect either the process of epithelial to mesenchymal transition (EMT) or mesoderm cell migration. In addition, it did not interfere with separation of smooth muscle cell progenitors from hemangioblasts. Moreover, natriuretic peptide receptor A (NPRA) has been identified as the putative target for glipizide׳s inhibitory effect on vasculogenesis. When NPRA was overexpressed or activated, blood island formation was reduced. NPRA signaling may play a crucial role in the effect of glipizide on vasculogenesis during early embryonic development.

Effect of CYP2C9 gene polymorphisms on response to treatment with sulfonylureas in a cohort of Egyptian type 2 diabetes mellitus patients

Oral hypoglycemics are a widely prescribed group of drugs for the management of type 2 diabetes mellitus. Sulfonylureas (SUs) are the cornerstone of type 2 diabetes pharmacotherapy. The enzyme cytochrome P450 2C9 (CYP2C9) is the main enzyme that catalyzes the biotransformation of SUs. It is encoded by the polymorphic gene CYP2C9 with two allelic variants namely CYP2C9*2 and CYP2C9*3 coding for variant allozymes with reportedly decreased metabolic capacity resulting in decreased SUs clearance and consequently prolonged and exacerbated action. The aim of this study was to investigate the influence of genetic polymorphisms of CYP2C9 on the response to glibenclamide, a second-generation sulfonylurea. Hundred type 2 diabetic patients were enrolled in the study. Genotyping was done on the LightCycler 2 by real-time polymerase chain reaction (PCR) hybridization probe assay. The results are the following: 53 patients were carriers of the wild genotype (CYP2C9*1/*1), 20 were heterozygous for the variant CYP2C9*2 allele (CYP2C9*1/*2), 18 were heterozygous for the variant CYP2C9*3 allele (CYP2C9*1/*3), and 9 were double heterozygous for both mutant alleles (CYP2C9*2/*3); of those double mutant genotype patients, two were also homozygous for the mutant CYP2C9*2 allele (CYP2C9*2/*2) and one patient was homozygous for the mutant CYP2C9*3 allele (CYP2C9*3/*3). Although there was no significant difference in drug dosage between the four groups, there was however a significant association of the CYP2C9*2/*3 genotype with better glycemic control. As conclusion, the better glycemic control observed can probably be attributed to slower metabolism of SUs by the carriers of the CYP2C9*2/*3 genotype and consequently longer half-life or exacerbated effect of the SUs administered.

FORMULATION AND IN-VITRO EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OF GLIPIZIDE

Diabetes mellitus is a metabolic disorder caused by insufficient production of endogenous insulin, with or without resistance to insulin action, resulting in hyperglycaemia. In type 1 diabetes mellitus, there is a failure in production of insulin as a result of destruction of the cells of the pancreas, and patients require treatment with insulin whereas type 2 diabetes can be characterised by defects in both insulin action (i.e. insulin resistance) and insulin secretion, and is associated with elevated basal hepatic glucose production. Glipizide is a second-generation sulfonylurea that can acutely lower the blood glucose level in humans by stimulating the release of insulin from the pancreas and is typically prescribed to treat type II diabetes. Different formulations were prepared by varying the concentration of HPMC used as polymers. The effect of varying concentration of hydrophilic polymers (HPMC 5cps and 15 cps) was studied on the release pattern of glipizide. Sustained release glipizide matrix tablets were prepared by wet granulation and compression of hydroxypropylmethyl cellulose (5 cps and 15 cps), drug and other excipients mixture. The promising formulation was compared with the marketed sample of suatained release glynase in terms of release pattern. The release rate of a glipizide from matrix tablet was decreased with increasing the concentration as well as viscosity polymer. This might be probably due to increased swelling and reduced erosion rate of matrix tablet. The formulation 13 (F13) showed the similar result as marketed sample of sustained release glynase tablets in terms of release rate. Key Words: Glipizide, Hydroxy propyl methyl cellulose (HPMC), Viscosity grades

Synthesis, Antidiabetic and Hypolipidemic Activities of New Diethylamine and Triethoxysilyl Derivatives of Tolbutamide on Rats

Tolbutamide (N-[(butylamino)carbonyl]-4-methylbenzenesulfonamide, CAS 64-77-7, I) is the first generation of potassium channel blocker and sulfonylurea oral hypoglycemic drug that imparts marked blood glucose lowering effect in type 2 diabetes or non-insulin dependent diabetes mellitus (NIDDM) patients. In this study, I and its two new analogs with substituting butylamine side by 3-diethylamino-1-propylamine (3) and 3-triethoxysilyl-1-propylamine (4) were synthesized and their antidiabetic and hypolipidemic activities were evaluated applying known procedures, and compared with both I and glibenclamide (II, well known second-generation sulfonylurea antidiabetic drug). The results showed that these new drugs (III and IV) were more potent than I and II and it could be concluded that changing the amine side of I would produce more potentials in new drugs (III and IV) of the first generation, to be named as the third generation. Also investigations on hypoglycemic and lipid lowering effects of these drugs proved that IV could reduce glucose, triglyceride (TG) and a low density lipoprotein (VLDL) level in blood serum more than others (I-III), 16 days after STZ injection.

Glimepiride: evidence-based facts, trends, and observations

Glimepiride: evidence-based facts, trends, and observations Abdul Basit, Musarrat Riaz, Asher FawwadDepartment of Medicine, Baqai Institute of Diabetology and Endocrinology, Baqai Medical University, Karachi, PakistanAbstract: Type 2 diabetes mellitus is characterized by insulin resistance and progressive β cell failure; therefore, β cell secretagogues are useful for achieving sufficient glycemic control. Glimepiride is a second-generation sulfonylurea that stimulates pancreatic β cells to release insulin. Additionally, is has been shown to work via several extra pancreatic mechanisms. It is administered as monotherapy in patients with type 2 diabetes mellitus in whom glycemic control is not achieved by dietary and lifestyle modifications. It can also be combined with other antihyperglycemic agents, including metformin and insulin, in patients who are not adequately controlled by sulfonylureas alone. The effective dosage range is 1 to 8 mg/day; however, there is no significant difference between 4 and 8 mg/day, but it should be used with caution in the elderly and in patients with renal or hepatic disease. In clinical studies, glimepiride was generally associated with lower risk of hypoglycemia and less weight gain compared to other sulfonylureas. Glimepiride use may be safer in patients with cardiovascular disease because of its lack of detrimental effects on ischemic preconditioning. It is effective in reducing fasting plasma glucose, post-prandial glucose, and glycosylated hemoglobin levels and is a useful, cost-effective treatment option for managing type 2 diabetes mellitus.Keywords: antihyperglycemic agents, diabetes, glimepiride, sulfonylurea

Glimepiride: evidence-based facts, trends, and observations (GIFTS). [corrected

Type 2 diabetes mellitus is characterized by insulin resistance and progressive β cell failure; therefore, β cell secretagogues are useful for achieving sufficient glycemic control. Glimepiride is a second-generation sulfonylurea that stimulates pancreatic β cells to release insulin. Additionally, is has been shown to work via several extra pancreatic mechanisms. It is administered as monotherapy in patients with type 2 diabetes mellitus in whom glycemic control is not achieved by dietary and lifestyle modifications. It can also be combined with other antihyperglycemic agents, including metformin and insulin, in patients who are not adequately controlled by sulfonylureas alone. The effective dosage range is 1 to 8 mg/day; however, there is no significant difference between 4 and 8 mg/day, but it should be used with caution in the elderly and in patients with renal or hepatic disease. In clinical studies, glimepiride was generally associated with lower risk of hypoglycemia and less weight gain compared to other sulfonylureas. Glimepiride use may be safer in patients with cardiovascular disease because of its lack of detrimental effects on ischemic preconditioning. It is effective in reducing fasting plasma glucose, post-prandial glucose, and glycosylated hemoglobin levels and is a useful, cost-effective treatment option for managing type 2 diabetes mellitus.

EVALUATION OF ENTRAPMENT EFFICIENCY OF GLIPIZIDE MICROSPHERE

INTRODUCTION Glipizide is a second-generation sulfonylurea that acutely lowers the blood glucose level in humans by stimulating the release of insulin from the pancreas and it is prescribed to treat type II diabetes (non-insulindependent diabetes mellitus). Its short biological half-life (3.4 6 0.7 hours) necessitates that it be administered in 2 or 3 doses of 2.5 to 10 mg per day.18 Thus, the development of controlled-release dosage forms would clearly be advantageous. So we have formulated oral controlledrelease products of glipizide by various techniques. Moreover, the site of absorption of glipizide is in the stomach. Dosage forms that are retained in the stomach would increase the absorption, improve drug efficiency,and decrease dose requirements. Thus, an attempt was made in this investigation to use chitosan as a mucoadhesive polymer and prepare microspheres.

Simultaneous determination of glimepiride and its metabolites in human plasma by liquid chromatography coupled to a tandem mass spectrometry

Glimepiride, a second-generation sulfonylurea, is a glucose-lowering agent widely used to treat diabetes mellitus. It is converted into metabolite M1 by CYP2C9, and M1 is then transformed into the carboxyl derivative M2 by cytosolic enzymes. In this study, we introduce a sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for determining glimepiride, M1, and M2 in human plasma. After simple protein precipitation with acetonitrile, the analytes were chromatographed on a reversed-phase CN column with a mobile phase of 10 mM ammonium acetate aqueous solution and acetonitrile (1:1, v/v). The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. This method was used to measure the concentrations of glimepiride, M1, and M2 in plasma after a single oral 2-mg dose of glimepiride in volunteers.

Pengembangan Sistem Penghantaran Obat Solid Self-Emulsifying Mikropartikel Gliklazid untuk Meningkatkan Disolus

Gliclazide is a Hypoglycemicdrug, second-generation sulfonylurea used in the treatment of non insulin dependent diabetes mellitus. Gliclazide exhibit poor aqueous solubility, so that their low bioavailability. Objectivesthis study is to develop solid self-emulsifying (SE) microparticles of poorly soluble gliclazide to dissolution enchancement. These microparticles were prepared by spray drying method, using three surfactant (acripol, tween 80n and sodium lauryl sulphate) with various concentration. SE microparticles characterized in terms of morphology (SEM),n particle size distribution (PSA), x-ray diffraction (XRD), thermalanalysis (DSC), functional group analysis (FTIR), solubility test,n and dissolution test. The all gliclazide SE microparticlesexhibited particle size smaller than pure gliclazide. The dissolution rate of gliclazide SE microparticles at one hour was increased about 2 to 3 times than gliclazide.

Galactomannan gum coated mucoadhesive microspheres of glipizide for treatment of type 2 diabetes mellitus: In vitro and in vivo evaluation

Type 2 diabetes mellitus is a heterogeneous disease of polygenic origin and involves both defective insulin secretion and peripheral insulin resistance. Studies have shown that post-meal hyperglycemic spikes are associated with increased cardiovascular mortality in type 2 diabetes. Over the past decade, a major interest in control of postprandial glucose excursion has emerged and a plethora of new medications that specifically target postprandial hyperglycemia were discovered. Despite the availability of new agents for treatment of type 2 diabetes mellitus, oral sulfonylureas remain a cornerstone of therapy, because they are relatively inexpensive and are well tolerated. However, hypoglycemia is a major safety concern with sulfonylureas and it is one major risk factor requiring hospitalization. Glipizide is a potent, rapid-acting with short duration of action and well tolerated second-generation sulfonylurea effective in reducing postprandial glucose levels. However, risk of postprandial hypoglycemia and post-meal glucose excursions, if dose missed before meal; are always associated with the use of glipizide for treatment of type 2 diabetes mellitus. Since, the site of absorption of glipizide is from stomach thus dosage forms that are retained in stomach by mucoadhesion; would increase absorption, improve drug efficiency and decrease dose requirements. Microsphere carrier systems made by using polymer galactomannan having strong mucoadhesive properties and easily biodegradable could be an attractive strategy to formulate. The purpose of this research work is to formulate galactomannan coated mucoadhesive microspheres of glipizide and systematically evaluate its in vitro characteristics and in vivo performance for sustained glucose lowering effect and improvement in diabetic condition as compared to immediate release of glipizide.

The role of glimepiride in the treatment of type 2 diabetes mellitus

Importance of the field: Type 2 diabetes mellitus (T2DM) is increasingly prevalent throughout the world; controlling glycemia is an important part of preventing serious complications of diabetes. Sulfonylureas have been used in the treatment of type 2 diabetes for many years.Areas covered in this review: This article reviews the pharmacological and clinical aspects of glimepiride, a second-generation sulfonylurea. Literature search was conducted in PubMed, and articles selected for relevance to pharmacology or clinical efficacy data from 1994 to 2009, with older references sought as indicated.What the reader will gain: Pharmacology of glimepiride, data regarding clinical efficacy, key comparisons to other agents and emerging concepts related to glimepiride are discussed.Take home message: Therapy with glimepiride improves the relative insulin secretory deficit found in T2DM, has antihyperglycemic efficacy equal to other secretagogues with reduced potential for hypoglycemia and may have additional actions contributing to glycemic control in T2DM.