Metformin Research Articles

Ternary Blend of Chitosan/Polyvinyl Alcohol/Carboxymethylcellulose as an Efficient System for the Release Studies of Metformin Hydrochloride

AbstractChitosan (CS) has attracted substantial attention as a sustainable biopolymer in drug delivery applications, in recent years, because of its nontoxicity, biocompatibility, and accessibility. This study develops chitosan/polyvinyl alcohol/carboxymethylcellulose (CS/PVA/CMC) ternary hydrogel with excellent efficacy as a potential delivery vehicle for the antidiabetic drug metformin hydrochloride. The incorporation of carboxymethylcellulose (CMC) in the blend remarkably improves the swelling properties of the hydrogel. Metformin hydrochloride is loaded in the CS/PVA/CMC ternary blend by ultrasonication method. The prepared hydrogel beads are characterized by, Fourier‐transform infrared spectroscopy (FT‐IR), Scanning electron microscopy (SEM), and X‐ray diffraction (XRD) techniques and confirm the presence of the drug in the beads. The loading and release of metformin from the CS/PVA/CMC hydrogel beads are followed by UV–visible spectroscopy at 233 nm. Different formulations are prepared by varying the compositions of chitosan and carboxymethylcellulose. α‐Glucosidase inhibitory studies reveal that metformin loaded CS/PVA/CMC hydrogel beads show excellent antidiabetic activity. The maximum value of inhibitory activity observed is 89%. Cytotoxic analysis proves that the beads prepared are nontoxic.

Methylene Blue in Metformin Intoxication: Not Just Rescue But Also Initial Treatment.

Metformin (MTF) is a widely used oral antidiabetic medication. Regardless the reason, high doses of MTF cause lactic acidosis as a result of its effects on mitochondrial ATP production and no-mediated vascular smooth muscle relaxation. Metformin-associated lactic acidosis can be life-threatening despite all treatments. Methylene blue (MB) has the potential to reverse the toxic effects of MTF through its effects on both the mitochondrial respiratory chain and nitric oxide production. The use of MB in MTF intoxication has only been reported in a limited number of cases. Herein, we present a 16-year-old female patient who attempted suicide by ingesting high doses of MTF. Supportive treatments, such as vasopressor, inotropic treatments, and sodium bicarbonate, were started in the patient who developed fluid-resistant hypotension after pediatric intensive care unit admission. Because of rising lactate levels, Continuous renal replacement therapy (CRRT) was started immediately. Despite all treatments, hypotension and hyperlactatemia persisted; MB was given as a rescue therapy. Noticeable hemodynamic improvement was observed within 30 minutes of initiating MB infusion, allowing a gradual decrease in the doses of inotropic infusions within the first hour of therapy. Patient's cardiovascular support was discontinued on the second day, and she was discharged on the fifth day. We speculate that, considering the mechanisms of MTF toxicity and the mechanisms of action of MB, it is suggested that early administration of MB, not only as a rescue treatment but as the initial approach to MTF poisoning in combination with other treatments, may result in improved outcomes.

The impact of metformin on weight and metabolic parameters in patients with obesity: A systematic review and meta-analysis of randomized controlled trials.

There are conflicting data on the weight-reducing potential of metformin (MTF) in nondiabetic patients with obesity. The purpose of this systematic review and meta-analysis was to evaluate the effect of MTF on weight and cardiometabolic parameters in adults with overweight/obesity with or without nonalcoholic fatty liver disease (NAFLD) (CRD42018085512). We included randomized controlled trials (RCTs) in adults without diabetes mellitus, with mean body mass index (BMI) ≥ 25 kg/m2, with or without NAFLD, comparing MTF to placebo/control, lifestyle modification (LSM) or a US Food and Drug Administration-approved anti-obesity drug, reporting on weight or metabolic parameters, and extending over at least 3 months. We conducted a systematic search in MEDLINE, EMBASE, PubMed and the Cochrane Library without time limitation (until March 2022). We screened and selected eligible articles, abstracted relevant data, and assessed the risk of bias. All steps were in duplicate and independently. We conducted a random-effects model meta-analysis using Review Manager version 5.3, with prespecified subgroup analyses in case of heterogeneity. We identified 2650 citations and included 49 trials (55 publications). Compared to placebo, MTF was associated with a significant reduction in BMI (mean difference [MD] -0.56 [-0.74, -0.37] kg/m2; p < 0.0001), at doses ranging from 500 to 2550 mg/day, and with a significant percentage change in BMI of -2.53% (-2.90, -2.17) at the dose 1700 mg/day. There was no interaction by baseline BMI, MTF dose or duration, nor presence or absence of NAFLD. There was no significant difference between MTF and LSM. Orlistat was more effective than MTF (at doses of 1000-1700 mg/day) in terms of weight loss, with an MD in BMI of -3.17 (-5.88; -0.47) kg/m2, favouring the former. Compared to placebo/control, MTF improved insulin parameters, while no effect was detected when compared to LSM. A few small trials showed heterogenous effects on liver parameters in patients with NAFLD treated with MTF compared to placebo/control. There was a large variability in the expression of outcome measures and RCTs were of low quality. In conclusion, MTF was associated with a modest weight reduction in obese nondiabetic patients. Further high-quality and better powered studies are needed to examine the impact of MTF in patients with insulin resistance and NAFLD.

Metformin-Mediated Improvement in Solubility, Stability, and Permeability of Nonsteroidal Anti-Inflammatory Drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are class II biopharmaceutics classification system drugs. The poor aqueous solubility of NSAIDs can lead to limited bioavailability after oral administration. Metformin (MET), a small-molecule compound, can be used in crystal engineering to modulate the physicochemical properties of drugs and to improve the bioavailability of orally administered drugs, according to the literature research and preliminary studies. We synthesized two drug-drug molecular salts (ketoprofen-metformin and phenylbutazone-metformin) with NSAIDs and thoroughly characterized them using SCXRD, PXRD, DSC, and IR analysis to improve the poor solubility of NSAIDs. In vitro evaluation studies revealed that the thermal stability and solubility of NSAIDs-MET were substantially enhanced compared with those of NSAIDs alone. Unexpectedly, an additional increase in permeability was observed. Since the structure determines the properties, the structure was analyzed using theoretical calculations to reveal the intermolecular interactions and to explain the reason for the change in properties. The salt formation of NSAIDs with MET could substantially increase the bio-absorption rate of NSAIDs, according to the in vivo pharmacokinetic findings, which provides an experimental basis for developing new antipyretic and analgesic drugs with rapid onset of action.

Metformin hydrochloride: The most prescribed treatment for type II diabetes -gets banned

Metformin hydrochloride (MH) is synthesis of N, N-dimethylguanidine medicament which is used for the treat of type-II diabetes which was discovered by Emil Werner and James Bell, which belongs to BCS class III. MH is chosen first-line oral blood glucose-lowering medication for the treatment of type-II diabetes, almost around 120 million patients are using worldwide. It works by decreasing the hepatic glucose production through a mild inhibition of mitochondrial respiration chain complex. MH which has been further tested and also proven that it can be used for various treatments such as, weight loss, improving fertility, slow the growth of tumour, anti-malaria, and few others. MH is synthesis from Galega officinalis which is a perennial plant that blooms in the summer and is native to most temperate areas. In this study, complete information about the drug history, drug profile, pharmacokinetic, drug interaction, clinical symptoms, advantages &amp; disadvantages of MH and reason why its getting banned has been explained in detail.

The feasibility of Raman spectroscopy for accurate assessment of essential criteria in pharmaceutical industry by investigation of Metformin hydrochloride tableting process

AbstractAnalytical and real‐time technology in pharmaceutical manufacturing process is an important need to ensure that manufactured drugs are safe and effective. Raman spectroscopy is an emerging technique that is able to perform quantitative analysis nondestructively due to the molecular structure of many drugs. Monitoring the content uniformity and quantification of active pharmaceutical ingredient (API) in the tablet preparation process, without the assistance of solvent, is one of the key concerns in the formulation design in order to provide stable, pure, and homogenous finished products. In this study, we investigated the possibility of using Raman data as an analytical method to quantify API, the intra‐ and inter‐sample uniformity of content in the tableting process of Metformin hydrochloride tablets (C4H11N5.HCl). Analysis of all standard samples for prediction of API uniformity represents an acceptable accuracy and precision with a relative standard deviation of 2.55%. Further investigation of tablets regarding to relative Raman intensity of some characteristic peaks demonstrates the amount of API content with an accuracy of ≥96%. These values have a good adaption with pharmacopeia monograph. Findings reveal that the Raman method can be routinely utilized for quantifying API, controlling the content uniformity and the stability of drugs in different stages of manufacturing.

Stimulus-responsive nanomedicine mediated by metabolic intervention mechanisms to amplify redox anticancer therapy

Metabolic reprogramming and altered redox balance are two common hallmarks of cancer. Redox homeostasis is intricately intertwined with tumor energy metabolism, but the potential for metabolic intervention mechanisms to disrupt redox balance has been consistently underestimated. In this study, we present a stimulus-responsive nanocarrier (NC) designed to leverage metabolic intervention mechanisms to enhance redox-based anticancer therapy. These nanoparticles are composed of zeolitic imidazolate framework-90 (ZIF-90) as the ATP- and pH-responsive porous core, enveloped in an amphiphilic pluronic 407 (poloxamer F127) coating to ensure steric stabilization. Within the core of these hybrid NCs, we co-loaded active cargos 3-bromopyruvate (3-BrPA) and metformin (MET). Serving as a multifaceted inhibitor of both aerobic glycolysis and respiration, 3-BrPA impedes the activities of hexokinase II, leading to reduced glucose consumption and an increase in ROS levels. This synergistic effect, in conjunction with MET, results in a decrease in the levels of reducing substances, sensitizing 3-BrPA-induced apoptosis in cancer cells. At both the cellular and animal levels, these hybrid NCs have demonstrated superior anticancer activity by inhibiting metabolism and disrupting redox homeostasis. This study introduces a novel approach targeting the metabolism-redox interplay for tumor treatment, potentially broadening the scope of available antitumor strategies.

Correction of endothelial dysfunction in patients with type 2 diabetes mellitus, diabetic kidney disease and non-alcoholic steatohepatitis

Background. Non-alcoholic fatty liver disease and chronic kidney disease are public health concerns worldwide due to their increasing prevalence, adverse prognosis, and health care burden. The purpose of the study was to determine the probable effect of a combination of metformin, rosuvastatin, essential phospholipids and quercetin on the blood lipids, endothelial function, fibrinolysis system and platelet hemostasis, which are factors for the progression of nonalcoholic steatohepatitis. Materials and methods. Studies were performed on the dynamics of treatment in 60 patients with non-alcoholic fatty liver disease, type 2 diabetes mellitus and diabetic kidney disease (stage I–III). Depending on the prescribed treatment at random, the examined patients were divided into 2 groups. Twenty-eight persons of the first group received a low-calorie diet with dietary restrictions, essential phospholipids, metformin hydrochloride, rosuvastatin. Thirty-two patients from the second group received quercetin in addition to similar dietary recommendations, essential phospholipids, hypoglycemic and hypolipidemic therapy. The mean age of patients was 53.80 ± 3.52 years. The comparison group consisted of 30 healthy individuals of the corresponding age. Results. To evaluate the degree of endothelial-protective effect of quercetin on the background of the recommended protocol therapy, markers of endothelial dysfunction, fibrinolysis and platelet hemostasis were studied. NO content significantly reduced (1.7 times) in patients of group 2 before treatment, increased by 1.5 times (p &lt; 0.05). This can be explained by the effect of quercetin, as well as the use of metformin, which reduces the degree of insulin resistance and the level of hyperlipidemia. Conclusions. The effectiveness of a combination therapy for non-alcoholic steatohepatitis and type 2 diabetes mellitus with diabetic kidney disease using essential phospholi­pids, statins and metformin with the addition of quercetin is higher than that of traditional therapy, as it significantly restores the functional state of the endothelium, eliminates the phenomena of hypercoagulation syndrome without the additional prescription of antiplatelet agents.

Evaluation of the Ejection Pressure for Tracking Internal Cracks during Compaction in Bilayer Tablet Formulations Using Experimental and Finite Element Methods.

This study aimed to evaluate the ejection pressure and the correlation of the findings with the occurrence of internal cracks within bilayer tablets (BLTs) consisting of metformin HCl (MF) and evogliptin tartrate (EG). Then, the mechanism of tablet failure was provided by the finite element method (FEM). The ejection pressure and the difference in diameter depending on MAIN-P were evaluated to understand the correlation between ejection pressure and change in the BLT internal structure. The ejection pressure and the difference in diameter increased as the MAIN-P increased, then steeply decreased from 350 MPa to 375 MPa of MAIN-P, despite there being no pattern in compaction breaking force and porosity. The mechanical integrity at the BLT interface was weakened by internal cracks, reducing ejection pressure. The stress distribution analysis during the compression revealed that crack formation caused by entrapped air located at the center of the BLT interface may not propagate due to concentrated stress, which promotes a tight bond at the edge of the BLT. Furthermore, complete delamination can occur in the ejection process due to localized and intensive shear stresses at the BLT interface. These findings indicate that the mechanisms of internal cracking and delamination were successfully confirmed by FEM simulation. Moreover, measuring ejection pressure before BLT manufacturing can prevent invisible tablet cracks without damaging the tablets.

Analytical quality by design approach for the development of high-performance liquid chromatography method for simultaneous analysis of metformin and sitagliptin in the presence of major degradation products.

An analytical quality by design-based high-performance liquid chromatography method for determining metformin (MET) and sitagliptin (SIT) in stress-degraded samples was developed and validated. The analytical target profile and risk assessment-driven critical method variables, for example, pH, % aqueous, and buffer concentration, were studied for their effect on method responses of retention time and resolution using a central composite design. The correlation regression coefficient was more than 0.8, and variables interaction was significant on method responses with curvature effect. The method operable design region afforded an aqueous range of 55%-70% and an ortho-phosphoric acid buffer of 0.1% with a pH of 3.0-4.0 as a robust region for the suitable method performance characteristics. The separation of MET and SIT from their degradants (m/z 85.0509; m/z 193.0694) on the C8 column was achieved using a mobile phase consisting of 0.1% ortho-phosphoric acid and methanol (60:40% v/v; pH 3.0). The optimized method eluted MET and SIT at 4.3±0.2 and 7.1±0.2min, respectively, with acceptable specificity and resolution. The linearity ranges of 25-250μg/mL (r2 : 0.9982) and 5-50μg/mL (r2 : 0.9989) was established for MET and SIT, respectively. The % recovery (98.81%-102.17%), precision (0.55%-1.65%), and robustness study for method variables were acceptable.

Improved synthesis of metformin hydrochloride-sodium alginate (MH-NaALG) microspheres using ultrasonic spray drying

Metformin Hydrochloride (MH), an orally administered antidiabetic drug from the biguanide family, encounters issues of wide particle size distribution, inefficient dissolution rates and short half-life leading to excess dosage which can result in lactic acidosis. Novel approaches that yield smaller particle size and uniform distribution at higher yields are significant to tackle problems associated with solubility and optimum dosage levels of the administered drugs. In the current research related to microsphere synthesis, a controlled process based on pressure and ultrasonic nozzles for the atomization of liquid, was applied with an objective of optimizing particle size of microspheres of MH in sodium alginate, a biopolymer excipient matrix. The study carried out in spray dryer elucidated parameter optimization using one variable at a time approach by varying important parameters as inlet temperature of air (120°C–150 °C), rate of flow of feed (1.5 mL/min-3 mL/min), aspirator rate (800 rpm–1400 rpm) and polymer content in feed solution (1 g–8 g) using ultrasonic and pressure nozzles for comparison with the target output parameter as particle size and yield. While the particle size at optimum conditions were <10 μm for both types of atomization, ultrasound assisted spray drying exhibited narrower distribution compared to the pressure atomization. Particle characterization performed using SEM, optical microscopy, FTIR, XRD and DSC revealed slight deformation with no chemical interaction and slight decrease in crystalline nature of pure drug. Overall, an improved process based on the use of ultrasound with optimized parameters has been demonstrated for synthesis of MH containing microspheres.

Vitis vinifera L. seed standardized extract; a promising therapeutic against metabolic syndrome induced by high-fat/high-carbohydrate diet and streptozotocin in rats

Metabolic syndrome (MetS) is a group of abnormal disorders; hypertension, glucose intolerance, dyslipidemia, proinflammatory, and prothrombotic states, affecting approximately 14 % of the world's population. The potential of grape seeds extract (GSE) supplementation to improve the metabolic disturbances and their related conditions like obesity, type 2 diabetes, and nonalcoholic fatty liver disease was investigated in this study. In-vitro metabolic syndrome assays were investigated through α-amylase, α-glucosidase, lipase, lipoxygenase (LOX), cyclooxygenases (COX-1 and COX-2), renin and angiotensin converting enzyme (ACE) inhibition assays. Additionally, in-vivo rat model of high-fat-high-carbohydrate diet (HFD)-induced MetS was established, where metformin (MT) (200 mg/kg) was used as a reference drug and GSE was given at 100 and 200 mg/kg by oral gavage. GSE was standardized using HPLC analysis for the major reported compound; catechin which should be ≥ 160.76 ± 5.52 μg/mL. Total phenolic content of GSE was 21.12±0.61 µg gallic acid equivalent/1 mg extract and total flavonoid content was 23.81±0.64 µg rutin equivalent/1 mg extract. In-vitro assays revealed the potential of GSE to manage the metabolic syndrome, besides its strong antioxidant capacity. Treatment with GSE (100 mg/kg and 200 mg/kg) markedly (P < 0.05) controlled the weight gain, improved the metabolic pathways (total glucose, cholesterol, triglycerides, AST, and ALT), oxidative stress parameters (MDA, GSH, and catalase) and inflammatory biomarkers in HFD fed rats. GSE downregulated the expression of insulin resistance gene (IR) and some inflammatory related genes (TNF-α and NF-κB), additionally it improved the pathological features of metabolic conditions and upgraded the expression of Nrf2 compared to HFD group. The superior effects were owned to the high dose of GSE, 200 mg/kg b.wt. (P < 0.05, P < 0.001). All results sustenance the beneficial effects of the standardized GSE in the management of metabolic syndrome.

COMPRESSION BETWEEN KAOLIN AND CORN SEED AS ADSORBENTS ON THE ADSORPTION OF METFORMIN HYDROCHLORIC FROM AQUEOUS SOLUTION UNDER DIFFERENT CONDITIONS

Metformin is currently the medicine used to treat hypoglycemia most frequently. We used kaolin and corn seed surfaces to draw out the drug metformin hydrochloride from aqueous solutions. The medicine metformin, which is currently the most frequently prescribed oral hypoglycemic, has outstanding safety profiles and is only contraindicated in people with definite medical problems, particularly chronic renal failure, congestive heart failure, chronic obstructive pulmonary disease, and liver disease. The analysis demonstrates how many factors, such as equilibrium time (5–15 min), pH (8.5) as well as for pH of small intestine, temperature (32–37°C). It is discovered that when temperature and pH increase, the amount of adsorbate present decreases, with equilibrium requiring 15 minutes. The wavelength used for the analysis of metformin HCl was (260 nm). To discover the appropriate adsorption parameters, it was chosen to apply response surface methodology (RSM). Through thorough physical characterization using techniques including FTIR it was demonstrated that the primary driving forces behind the adsorption processes are H-bonding, electrostatic attraction, and so-called (electron donor-acceptor) EDA interactions. Modeling revealed that the best explanation for the MF adsorption involved an isotherm that depended on Giles categorization, was spontaneous (ΔG = -5.9 kJ/mole), and was endothermic (ΔH = +12.14 kJ/mole).

Comparing Hydroxypropyl Methylcellulose and Guar Gum on Sustained Release Effect of Metformin Hydrochloride Matrix Tablet

Comparing Hydroxypropyl Methylcellulose and Guar Gum on Sustained Release Effect of Metformin Hydrochloride Matrix Tablet

Focus on the epidemiology, pathophysiology, diagnosis, and management of insulin dysregulation in horses

Because there are various inter-related disorders of insulin metabolism that all may contribute to the final result of hyperinsulinaemia, the phrase "insulin dysregulation" has become the most acceptable term to use when describing equine metabolic syndrome (EMS). Insulin dysregulation is widespread in horses, and it appears to be more prevalent in physically sedentary horses. Laminitis and hyperinsulinaemia have been linked, as have other components of insulin dysregulation. Diagnosis of insulin dysregulation should be done in stages, beginning with basal testing, which includes baseline values of insulin and glucose, and concluding with dynamic tests, which detect tissue insulin resistance and hyperinsulinaemia. Dietary adjustments are the key to weight loss in the majority of EMS horses. To encourage weight loss, the horse should be given around 1.25% of its body weight every day. Exercise not only aids equid weight loss but also improves insulin sensitivity. The exercise should be tailored to the specific horse, taking into account its breed, fitness level, and owner's resources. When an obese horse is unable to exercise owing to laminitis or when obesity persists after extensive exercise and dietary management, levothyroxine sodium and metformin hydrochloride can be given to help accelerate weight loss and increase insulin sensitivity. Insulin dysregulation is a defining feature of equine metabolic syndrome and has garnered attention due to its direct link to laminitis. There is need for an in-depth understanding of ID in order to prevent the development of clinical laminitis. The current study discusses the epidemiology, pathophysiology, diagnosis, and management of insulin dysregulation in horses.

Innovative approach for improved sustained delivery of metformin hydrochloride for its anti-hyperglycemic activity

Metformin hydrochloride, an antidiabetic agent, is useful in reducing the blood glucose concentration in Type II diabetes. It is also finding its use as a repurposed drug. The formulations consisted of micro drug delivery systems prepared by emulsification method and were evaluated in-vitro and in-vivo. Process variables like amount of polymer, speed of agitation and stirring, presence or absence of surfactant and cross linker offered a versatile approach towards obtaining the formulation though affected physicochemical properties of formulations. Discrete, spherical, and free-flowing microspheres, in the size range and granularity of 250 to 700µ were used to control the drug release rate. Drug release was diffusion controlled as evident from the Higuchi kinetics. The physical characteristics of the formulations were reproducible. Healthy and alloxan induced hyperglycaemic male albino mice were used for in-vivo experimentation by evaluating plasma glucose level reduction and % reduction in the blood glucose level after administration of pure drug and formulations. The results indicate significant sustained fall in the blood glucose level for about 10 hrs following formulation administration as compared to the pure drug.

Application of the variability budget approach to the Dissolution test

The aim. This study aimed to evaluate the completeness of our knowledge about the sources of variation in the Dissolution test with 100 % release by compiling a variability budget.&#x0D; Materials and methods. The study was performed on 500 mg metformin tablets, using pharmacopoeial quality reagents, State Pharmacopoeia of Ukraine (SPhU) Metformin HCl reference standard, Pharmatest DT70 Dissolution apparatus, Perkin Elmer Lambda 35 spectrophotometer, Mettler Toledo XP 204 analytical balance, and ISO class A volumetric glassware. The SPhU metrological approach was employed.&#x0D; Results and discussion. The variability budget was compiled based on the comparison of uncertainty estimates obtained from the requirements for maximum permissible variation in normal analytical practice (UNAP, bottom-up estimation) and experimental data (Uexp). This involved characterizing Metformin content in tablets using the Uniformity of Dosage Units (UDU) test as an independent method. The 100 % release of Metformin in the Dissolution test (infinity point) was proved by increasing the dissolution time. Having optimized Dissolution and UDU analytical procedures for variability budget compiling, we achieved insignificance of Uexp compared to the target uncertainty (Utg) for the Dissolution test in compliance testing. The differences in UDU and Dissolution mean results did not exceed UNAP for the release time of 45 and 60 min, i.e. uncertainty budget was proven. Uexp for the Dissolution test indicated the presence of an unknown statistically significant source of random variation, which, however, was less than Utg; therefore, the procedure is suitable for compliance testing.&#x0D; Conclusion. Experimental results confirmed the completeness of our knowledge about sources of variation (absence of bias) for the Dissolution test with 100 % release. An essential condition for compiling the budget was the optimization of uncertainty of analytical procedures. For UDU, all significant sources of variation were within the expected range. Yet, there is a need for additional research to identify and manage an unknown source of practically significant random variation for the Dissolution test

Validation and Application of Screen-Printed Microchip for Potentiometric Determination of Metformin Hydrochloride in Tablet Dosage Form.

Metformin is an oral biguanides hypoglycaemic agent, which used to lower the blood glucose levels in people with type 2 diabetes mellitus. Many analytical techniques have been used to quantify the drug in different pharmaceutical dosage forms; however, most of these methods have limited throughput in the quality control application. A disposable potentiometric microsensor responsive to metformin has recently been reported. For the first time, herein, this method of analysis has been validated according to IUPAC recommendations and successfully applied in the determination of metformin drug in some dosage form. Different drug formulations of metformin hydrochloride have been collected from the local pharmaceutical stores in Saudi Arabia and analysed using the validated microchip-based method of analysis. Subsequently, the results of this study showed that the validated method was linear, specific, precise, and accurate. The linear range was 1 × 10-1-1 × 10-5 mol L-1 and the correlation coefficient was 0.999. The limit of detection was 2.89 × 10-6 mol L-1, and the limit of quantification was 8.77 × 10-6 mol L-1. This method demonstrated high precision, with an RSD% of less than 2.22%. The accuracy of this method was obtained by comparing the recovery percentage with percentage values less than 5%. The results obtained showed that there was no significant difference between the references, label, and recovery of less than 5%.

Formulation and Evaluation of Extended Release Oral Suspension of Metformin Hydrochloride

The research scheme of formulation and evaluation of extended-release oral suspension of metformin hydrochloride with the objective to develop a stable, redispersible oral liquid suspension based on extended-release pellets to facilitate swallowing in patients with diabetes. Pellets were prepared by using Bed Coating During Sliding method with the Metformin hydrochloride used as antidiabetic drug and various polymers. Extended release was affected by the ethylcellulose coating of drug formulation used as coating agent, MCC, Lactose, PVP K-30 Prepared metformin hydrochloride pellets putted in to prepared sugar free syrup vehicle using polymers like Xanthan Gum as a suspending agent for uniform drug distribution, Sorbitol solution, Aspartame are artificial sweeteners, Sodium Citrate, Potassium sorbate, Methyl paraben. The formulation was optimized based on Design expert software and Central Composite Design was used for study. Drug and polymers were studied for compatibility and interaction study, carried out by FTIR and DSC and found to be compatible to each other. The Redispersibility, Sedimentation volume, Sedimentation rate, Rheological Study, Viscosity, Specific gravity, Particle Size, dissolution study and %Drug content of formulated batches was evaluated. All the results were within the acceptable pharmacopeial limits and were evaluated statistically by using one way ANOVA test for quadratic model. From the result, MET6 batch was observed optimized formulation because up to 8 hrs 85.25% drug was released. kinetic studies of the drug release for optimized formulation follows zero order kinetics.

A randomized, double-blind, active-controlled trial assessing the efficacy and safety of a fixed-dose combination (FDC) of MEtformin hydrochloride 1000 mg ER, SItagliptin phosphate 100 mg, and DApagliflozin propanediol 10 mg in Indian adults with type 2 diabetes: The MESIDA trial

ObjectiveTo assess the efficacy and safety of fixed-dose combinations (FDC) of triple-drug dapagliflozin, sitagliptin, and metformin (DSM) compared with FDC of two-drug sitagliptin and metformin (SM), in Indian adult patients with type 2 diabetes (T2D).MethodsA multicentric, randomized, double-blind, active-controlled, Phase 3 study (CTRI/2021/10/037461) was conducted on 274 Indian adult patients with T2D. Patients were randomized (1:1) to receive either an FDC of triple-drug (n = 137) dapagliflozin propanediol 10 mg, sitagliptin phosphate 100 mg, and metformin hydrochloride 1000 mg extended-release (DSM) or FDC of two-drug (n = 137) sitagliptin phosphate 100 mg and metformin hydrochloride 1000 mg sustained-release (SM), for 16 weeks. The primary endpoint was a change in HbA1c, while the secondary endpoints were changes in fasting plasma glucose (FPG), postprandial glucose (PPG), body weight, and safety.ResultsBoth DSM and SM FDCs reduced HbA1c significantly (-1.45% and -1.00%, respectively, both p < 0.0001), however, HbA1c lowering was superior with DSM (∆ -0.45%; p = 0.0005) compared to SM, at week 16. Similarly, both DSM and SM FDCs reduced FPG and PPG significantly, however, FPG (∆ -12.4 mg/dl; p = 0.003) and PPG reduction (∆ -18.45 mg/dl; p = 0.01) were significantly superior to DSM compared to SM, respectively. No significant reduction in body weight was observed between the two arms. Both FDCs were well tolerated.ConclusionFDC of DSM was superior to SM in reducing HbA1c, FPG, and PPG in Indian adults with T2D. Both triple and dual FDCs had optimal safety profiles.