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This study introduces an innovative, and rapid HPLC method using reverse phase elution for the simultaneous analysis of Sitagliptin and Metformin HCl in pharmaceutical formulations. This combination was explored in bulk and solid dosage forms using Luna Phenomenex C8 column (4.6 x 250 mm, 5 µm) at ambient temperature in isocratic elution. It was found that the mobile phase comprising of 0.1% ortho-phosphoric acid, potassium dihydrogen phosphate buffer (pH 3.0) and acetonitrile in ratios 35:35:30, showed a symmetrical peak for Sitagliptin and Metformin HCl. The detection was carried out at 210nm, using a flow rate of 1.0mL/min. The method was linear over the concentration range for Sitagliptin 2.5-7.5 ppm and Metformin HCl 25-75 ppm. The assay recoveries of Sitagliptin and Metformin were found to be 100.36% and 100.20%, respectively. The LOD and LOQ for the Sitagliptin were found to be 0.201 ppm and 0.301 ppm and for Metformin HCl 0.101 ppm and 0.303 ppm, respectively. The proposed methods can be implemented for controlling quality in bulk and solid dosage forms. The analytical methods were validated as per the guideline of ICH Q2 (R2). The developed HPLC methods were effectively employed for the determination of combined dosage forms in pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

This study aims to validate the method for measuring metformin hydrochloride plasma concentrations using High-Performance Liquid Chromatography (HPLC). This research performed chromatography on a 250 mm 4.6 mm 5 µm purosphere® Star RP-18 column at ambient temperature with a UV detector system at 233 nm. The mobile phase components were 70% phosphate buffer (KH2PO4) (10 mM), sodium dodecyl sulfate (0.3 mM), and 30% acetonitrile. It was pumped at an isocratic flow rate of 1.2 mL/min. Metformin HCl and ranitidine HCl (internal standard) were extracted using acetonitrile. The calibration curve was linear (R2 = 0.9998) in the 0.18–6 µg/mL concentration range. The lower limit of quantification (LLOQ) was 0.18 µg/mL. For intraday accuracy and precision, the percent difference and the coefficient of variation were less than 4 and 7%, and for inter-day were lower than 8 and 6%. The recovery average was 100.96%. The short-term plasma stability test was stable at 24 h at ambient temperature, and the long-term stability test was steady for 30 d at −20 °C. It was also stable after three freeze-thaw cycles. The method meets selectivity, sensitivity, linearity, accuracy, precision, recovery, carryover, and stability requirements and can be applied to population-based pharmacokinetic modeling.

The study aimed to evaluate the drug–drug, drug–polyvinyl alcohol, and drug–process incompatibilities for the manufacturing of metformin/sitagliptin fixed dose combinations. The melt manufacturing process is a solvent-free green process such as melt granulation, melt extrusion, and 3D printing by a fusion deposition method. The pre-formulation study was designed to explore compatibility using analytical techniques such as differential scanning calorimeter, high-performance liquid chromatography, and liquid chromatography coupled with high-resolution mass spectra. The drug substances and their physical mixture were subjected to different thermal cycles at 80 °C, 180 °C, and 250 °C. All the samples obtained from the thermal cycles were analyzed for assay by high-performance liquid chromatography. The identification of impurities was carried out by liquid chromatography coupled with high resolution mass spectrometry. The result of differential calorimetry studies reveals that there was no interaction between metformin and sitagliptin in the presence of polyvinyl alcohol up to 180 °C and a potential possibility for the interaction above 180 °C. However, a significant drop in the assay of all the sitagliptin samples at 180 °C was observed in high-performance liquid chromatography, which was further confirmed by mass spectra. The stability of metformin samples at 180 °C was confirmed by all the analytical techniques. The results obtained by this investigation reveal the possibility of manufacturing metformin formulations using the melt manufacturing process, but not for sitagliptin and its combinations. [ABSTRACT FROM AUTHOR]

The development of hydrophilic carriers with dual stimuli‐ responsiveness for the drug encapsulation and controlled release is one of the biggest challenges for the modern medicinal chemist. In this context, the current study explores the application of locust bean gum (LB), to develop a pH and temperature responsive matrix for controlled delivery of an anti‐diabetic drug, Metformin HCl (MFH) for the first time. LB gum was first structurally modified to carboxymethylated locust bean gum (CMLB). It was copolymerized with sodium acrylate (SA) and cross‐linked by using N,N‐methylene bisacrylamide (MBA) to form hydrogel (CMLB‐co‐poly(SA)‐cl‐poly(MBA)). The model hydrogel was examined using FTIR, TGA, SEM, XRD, and 13C‐NMR to determine structural changes, thermal behaviour and surface morphology. Network parameters confirm the porous nature of the hydrogel and support their swelling behaviour. The drug loaded CMLB‐co‐poly(SA)‐cl‐poly(MBA) hydrogel follows the non‐Fickian diffusion of the anti‐diabetic drug, Metformin HCl (MFH), which is having short and biological half life time. The MFH release profile was analysed by fitting data in the Korsmeyer‐Peppas kinetic model with high rate of release in pH 7.4 compared to Distilled Water (DW) and pH 2.2. Thus we can explore the bio‐compatible synthesized hydrogel as a carrier for sustained drug delivery. [ABSTRACT FROM AUTHOR]

In the current investigation, we have designed and assessed a simple and swift analytical approach employing UV spectroscopy for the simultaneous quantification of the analytes metformin and quercetin with excellent precision and accuracy. The wavelengths of interest are the wavelengths at which both the drugs show maximum absorbance: 233 nm for metformin and 256 nm for quercetin. Linearity study, conducted in methanol and phosphate buffer, yielded a correlation coefficient (r2) of 0.99. The validation study for the developed method was conducted in accordance with ICH Q2 R1 guidelines. The percent recovery was 95% to 105%, and the percent relative standard deviation was <2, demonstrating the accuracy and precision of this method. This method can be applied to analysis of the two compounds in fixed dose formulations using simple UV spectroscopy. [ABSTRACT FROM AUTHOR]

In the current study, the synthesis of hydrogel based on carboxymethyl tamarind kernel gum (CMTKG), poly(sodium acrylate) (PSA), xanthan gum (XG) and its loading with metformin hydrochloride (metformin HCl) was successfully carried out and characterized using various techniques. Furthermore, the optimization of hydrogel was done by varying the amount of carboxyl methyl tamarind kernel gum (CMTKG), N, N′-methylene-bis-acrylamide (MBA) or potassium persulphate (KPS), and their influence on the swelling ratio was examined. The fabricated hydrogels were characterized by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM), whereas thermal stability was confirmed by thermogravimetry analysis (TGA). The hydrogels' swelling ratio and in vitro drug release studies were assessed in pH 1.2 and 7.4 buffer solutions and showed better results in alkaline pH. The drug release profile of metformin-loaded CMTKG/PSA/XG hydrogel obeyed the Korsmeyer–Peppas model and follow non-Fickian diffusion in pH 7.4 and Fickian diffusion mechanism at pH 1.2. This pH-dependent behaviour of the metformin HCl-loaded CMTKG/PSA/XG hydrogel could be applicable for site-specific release of metformin HCl. [ABSTRACT FROM AUTHOR]

Abstract Background Nateglinide and metformin HCl are used in combination for the treatment of type 2 diabetes. A simple, sensitive and reliable UPLC method was developed for simultaneous estimation of nateglinide and metformin HCl using Phenomenox C18 (50*2.1 mm, 3.5 µm) column at ambient temperature as stationary phase in addition to mobile phase containing 75 volumes of ammonium formate buffer (pH = 3) along with 25 volumes of acetonitrile with a flow rate of 0.2 mL/min with UV detection at 260 nm and a run time of 3 min. The developed method was validated as per ICH Q2(R1) guidelines. Results The separation of metformin HCl and nateglinide was done at retention times of 1.014 min and 1.435 min, respectively. The mean % recovery for nateglinide and metformin HCl in the accuracy study was observed to be 99.9% and 99.2%, respectively. LOD and LOQ values were determined considering the S/N ratio and were found to be 0.09 µg/mL and 0.3 µg/mL, respectively, for nateglinide and 0.75 µg/mL and 2.5 µg/mL, respectively, for metformin HCl. The method was found to be precise with % RSD values of 0.58 and 0.45, respectively, for repeatability and intermediate precision of nateglinide and 0.43 and 0.43, respectively, for repeatability and intermediate precision of metformin HCl which were within acceptance criteria. The method was found to be linear in the range of 7.5–45 µg/mL and 62.5–375 μg/mL for nateglinide and metformin HCl, respectively. The regression equations for nateglinide and metformin HCl were found to be y = 17377x + 6543.4 and y = 18439x + 43,537, respectively. The method was found to be robust by deliberate changes in the method parameters like flow rate and mobile phase composition. Forced degradation studies were performed as per ICH Q1A(R2) and Q1B guidelines, and peak purity was observed in all types of degradation studies for both the drugs. Conclusion The developed method was found to be satisfactory as it is simple, sensitive, accurate, precise, robust, rapid, economical and yet stability indicating and can be applied successfully in the routine laboratory analysis for the simultaneous estimation of nateglinide and metformin HCl in the bulk and pharmaceutical dosage forms.

Introduction: Diabetes Mellitus (DM) is one of the most prevalent and chronic illnesses associated with an abnormally high level of glucose in the body which is hazardous to the body organs. Metformin Hydrochloride (HCl), a biguanide derivative is used for Type 2 DM. It has a relatively short plasma half-life and its regular administration is required to maintain a normal blood glucose level in diabetic patients. Therefore, sustained-release medications are a suitable approach to increase patient compliance and extend the duration of the effect of metformin for 8-12 hr. The main goal of this investigation was to prepare an oral sustained-release tablet of metformin HCl using natural polymers as release rate-controlling agents. Materials and Methods: Polymer fused metformin hydrochloride sustained-release tablet was formulated with sodium alginate, and pectin alone and in combinations at different ratios, by direct compression method. Evaluations: The formulation was evaluated for pre-compression parameters, like drug-excipient interaction (using Fourier-transform infrared spectroscopy), drug solubility, flow properties and density of powder blends. The compressed tablets were evaluated for diameter, friability, thickness, weight variation, hardness, content uniformity and in vitro drug release. Results: The drug release study showed that sodium alginate and pectin alone and in combination were able to sustain the drug release. It is also suggested that if the amount of polymer increased, the drug release decreased. Formulation (MA3) containing the highest amount of sodium alginate (250mg) gave 93.06% drug release after 12 hr and was therefore chosen as the best formulation. Diffusion and erosion may be the mechanism of drug release, according to the kinetic modelling of the in vitro drug release. [ABSTRACT FROM AUTHOR]

This study targets to prepare a metformin hydrochloride delivery system through the preparation and evaluation of 2-hydroxyl ethyl methacrylate (HEMA) based hydrogels. The current study explores the effect of photoinitiator (Irgacure 184, Irgacure 651), PEG-DA derivatives, 4-Acryloyl morpholine (4-AcM), and gelatine obtained by UV photopolymerization of HEMA hydrogels. Photopolymerization technique which was under UV irradiation was implemented at 365 nm and 300 s. Two different photoinitiators [2,2-Dimethoxy-2-phenyl-acetophenone (Irgacure 651)], [1-Hydroxycyclohexyl phenyl ketone (Irgacure 184)] were used to obtain the impact of photoinitiators on the metformin HCl release behavior of samples. In addition, PEG-DA Mn=258, PEG-DA Mn=700, 4-AcM, and gelatine were used to improve HEMA hydrogels. The prepared hydrogels have been characterized using Fourier transform infrared spectroscopy (FT-IR) and a digital microscope. The behaviors of hydrogels were specified by exploring swelling and release profiles in different medias. In-vitro metformin HCl release analyses have been done at pH 1.2, 6.8, and 7.4. UV-Vis spectrophotometer at 244 nm for releasing studies was used. The release results of hydrogels synthesized with Irgacure 651 demonstrated the majority quantity of the drug. Furthermore, the release amounts were higher in pH 1.2 than at mentioned pH medias before. [ABSTRACT FROM AUTHOR]

Introduction: The most common variety of lung cancer is non-small cell lung cancer (NSCLC) accounting for 84% of new cases. Surgery, chemotherapy and radiation are the primary treatment option. Metformin has recently been demonstrated to have an anti-tumour impact on various cancer cells. The goal of this investigation was to determine the growth inhibitory, antiproliferative, cytotoxic, apoptotic and cell cycle arrest properties of metformin HCl oral tablets on the A549 lung carcinoma cell line. Methods: The cells were treated with different dosages of an oral preparation of metformin, with untreated cells used as a control. The Trypan Blue Exclusion Assay was used to determine metformin's inhibitory and cytotoxic effects. Flow cytometry was used to evaluate apoptosis and cell cycle arrest. Results: In a dose-dependent manner, metformin HCl was able to reduce the viability of treated cells compared to the untreated control. Cell proliferation was considerably inhibited in the treated group with the IC50 dose than in the untreated control group and the IC50 dose showed no cytotoxic effect on L929 cells. Induction of apoptosis and cell cycle arrest was observed in the IC50 dose-treated group by Flow cytometry analysis and data showed metformin oral drug causes early apoptosis and a considerable cell increase in the S phase of the cell cycle. Conclusion: Metformin inhibits cell growth and induces apoptosis and cell cycle arrest in the cell line. A comprehensive proteome examination is required to understand more about the mechanism of action of the oral metformin HCl on cancer cells. [ABSTRACT FROM AUTHOR]

Repaglinide and Metformin are used to treat Type 2 diabetes. Repaglinide with poor water solubility has relatively low oral bioavailability (56%) and undergoes hepatic first-pass metabolism. The oral bioavailability of metformin HCl is also low (about 50-60%). The purpose of this study was to prepare nanoemulsion formulations containing metformin HCl or repaglinide alone or in combination and characterize them in vitro and in vivo. Nanoemulsion formulations containing metformin HCl and/or repaglinide were successfully prepared and in vitro characterized. In addition, in vivo efficacy of nanoemulsion formulations was evaluated in a streptozotocin-nicotinamide-induced diabetic rat model. Biochemical, histopathological, and immunohistochemical evaluations were also performed. The mean droplet size and zeta potential values of nanoemulsion formulations were in the range of 110.15±2.64-120.23±2.16 nm and -21.95 – -24.33 mV, respectively. The percent entrapment efficiency values of nanoemulsion formulations were in the range of 93.600%-96.152%. All nanoemulsion formulations had a PDI of ≤0.223. A statistically significant decrease was observed in the blood glucose values of the diabetic rats treated with nanoemulsion formulations containing active substance/substances, compared to diabetic rats (control) (p<0.05). Nanoemulsion formulations (especially nanoemulsion containing metformin HCl and repaglinide combination) have a better antidiabetic activity and are more effective in reducing oxidative stress caused by diabetes. [ABSTRACT FROM AUTHOR]

This study was aimed to develop and validate an HPLC-UV method for simultaneous analysis of metformin HCl (MET HCl) and repaglinide (REP) in nanoemulsion (NE) formulations and commercial tablets. MET HCl and REP-containing NE formulations (NE-1 and NE-2) were prepared. The droplet size and PDI values of NE formulations were found in the range of 100.631 ± 0.504–173.356 ± 2.432 nm and 0.128 ± 0.005–0.227 ± 0.004, respectively. Separation and analysis were performed on a C18 column (4.6 × 250 mm; 5 μm) using a mobile phase including methanol:ethanol:ultrapure water mixture at pH adjusted to 3.0 with formic acid (30:40:30, v/v/v) and 242 nm was used for UV detection. The method is linear in a concentration range of 1 – 48 μg/mL for both MET HCl and REP. The retention times of MET HCl and REP were found to be 2.1 and 8.2 min, respectively. The limits of detection (LOD) were 0.174 μg/mL for MET HCl and 0.210 μg/mL for REP. The limits of quantification (LOQ) were 0.526 μg/mL for MET HCl and 0.637 μg/mL for REP. The values of relative error and relative standard deviation (%) for both active substances were found to be lower than ± 2% and 2%, respectively. This method was successfully applied for the simultaneous analysis of MET HCl and REP in NEs and commercial tablets. [ABSTRACT FROM AUTHOR]

Abstract Flaxseed (Linum usitatissimum L.) is the seed of a multipurpose plant of pharmaceutical interest, as its mucilage can be used as a natural matrix to develop extended-release dosage forms and potentially replace synthetic polymers. In this study, a 3² factorial design with two replicates of the central point was applied to optimize the development of extended-release granules of metformin HCl. The total fiber content of the mucilage as well as the friability and dissolution of the formulations were evaluated. The lyophilized mucilage presented a high total fiber content (42.63%), which suggests a high efficiency extraction process. Higher concentrations of the mucilage and metformin HCl yielded less friable granules. In addition, lower concentrations of metformin HCl and higher concentrations of the mucilage resulted in slower drug release during the dissolution assays. The release kinetics for most formulations were better represented by the Hixson-Crowell model, while formulations containing a higher concentration of the mucilage were represented by the Korsmeyer-Peppas model. Nonetheless, five formulations showed a longer release than the reference HPMC formulation. More desirable results were obtained with a higher concentration of the mucilage (13-18%) and a lower concentration of metformin (40%).

Diabetes remains a global public health threat because of its increasing prevalence and mortality, especially in people under the age of 25. Metformin hydrochloride (HCl), as recommended by American Diabetes Association in 2022, is the first-line therapy for type 2 diabetes in adults. Metformin has low oral bioavailability due to poor permeability. Therefore, by developing metformin HCl oral in situ gel, sustained delivery of metformin can be achieved, thus enhancing the absorption of the drug. Sodium alginate and pectin were used for formulating the system. Different adjuvant polymers, including HPMC K4M, HPMC K100 LV, PEG 4000, and SCMC were used as released-pattern-modifying agents. All formulations could afloat in 0.1 N HCl at the pH of 1.2 within a minute and stay afloat for over 8 h. The optimized formulation could be made from either sodium alginate (2%) and HPMC K4M (0.5%) or pectin (2%) and HPMC K4M (2%). The optimized formulations gradually released metformin HCl with a cumulative release of 80% within 8 h. We successfully developed floating in situ gels that can release metformin HCl sustainedly.

The aim of this present work is to use polyvinyl alcohol (PVA) – gelatin-based hydrogel prepared by γ-rays irradiation with different gelatin concentrations ranging from 0.5 - 2 %w/v for immobilization of Metformin HCl (MH) at dose range of 0 - 30 mg. The mixture were freezed-thawed for 3 cycles, irradiated using γ-rays with sterilization dose at 25 kGy (dose rates 5 kGy/h). Gel fraction and water absorption were determined gravimetrically. The surface morphology of hydrogels were observed using Scanning Electron Microscope (SEM). In vitro release of MH were taken using UV-Vis spectrophotometer. After evaluated, it was found that with increasing gelatin concentrations, gel fraction increases and water absorption decreases. With increasing gelatin concentration and drug dosage, the cumulative drug released decreases. From SEM observation, the hydrogel had a heterogeneous porous. The hydrogel based on PVA-gelatin can be considered as a matrix for controlled drug release and safe for humans since both PVA and gelatin are non-toxic.

Hydrogels have been widely used in biomedical fields including tissue engineering, drug delivery and cell delivery and 3D cell delivery due to abundant water content in their hydrophilic three-dimensional networks and having soft tissue similar to the human body. In recent years, supramolecular hydrogels (SHG) formed by the inclusion complex between polyethylene glycol (PEG) and macrocycles such as cyclodextrin (CD) have attracted much interest due to their excellent biocompatibility and great potential in biomedical. In this research, a carboxymethyl cellulose (CMC)-based graft copolymer was prepared by using acrylic acid (AA) and maleic anhydride functionalized β-CD (β-CD-MA) as comonomers and ammonium persulfate (APS) as initiator. Then, a self-healable supramolecular hydrogel was synthesized by formation of a host-guest inclusion complex between CMC-g-poly (AA- co -β-CD-MA) as host molecule and cytosine- and guanine-modified PEG as guest molecules. The prepared hydrogel was characterized by Scanning Electron Microscope (SEM), X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Nuclear magnetic resonance spectroscopy (1H NMR). The thermal stability of hydrogel was also determined by thermal gravimetric (TGA) and differential scanning calorimetry (DSC) methods. In addition, the loading and release profiles of metformin hydrochloride (MH) drug as a model on hydrogel was investigated. The results indicated that the drug release from the hydrogel peaks around 360 min and aligns with the Ritger-Peppas model. The hydrogel's self-healing property was examined at ambient temperature and 37 °C. It showed 70 % healing in 1.5 h and completed recovery after 9 h. [ABSTRACT FROM AUTHOR]

Heba F Salem,1 Mohammed M Nafady,2 Adel A Ali,1 Nermeen M Khalil,2 Amani A Elsisi1 1Department of Pharmaceutics & Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; 2Department of Pharmaceutics, Faculty of Pharmacy, Nahda University, Beni-Suef, EgyptCorrespondence: Mohammed M Nafady, Department of Pharmaceutics, Faculty of Pharmacy Nahda University, Beni-Suef, 62511, Egypt, Tel +01100719792, Email Mohamednafady83@yahoo.com; Mohamednafady83@gmail.comIntroduction: Metformin hydrochloride (metformin HCL), a first-line drug treating diabetes type II, was known to cause severe gastritis, so seeking a non-oral dosage form was the new trend. Bilosomes are bilayer nano-vesicles of non-ionic surfactants embodying bile salts. In our study, bilosomes were investigated as an acceptable novel carrier for active targeting transdermal delivery of metformin HCL, circumventing its side effects.Methods: Twelve bilosome formulations were prepared with solvent evaporation method with slight modification according to a 31 .22 full factorial design, and the optimized formulation was determined using Design -Expert 13 software (Stat-Ease, Inc., Minneapolis, Minnesota, USA) studying the effect of surfactant and bile salt types on the entrapment efficiency (EE), vesicle size (VS), polydispersity index (PDI), zeta potential (ZP), percentage of drug released within 24 h (R), and flux of drug permeated within 6 h (Jss) of vesicles. In addition, the optimized formulation was further evaluated to Fourier-transform infrared spectroscopy (FTIR), deformability index (DI), and transmission electron microscope (TEM) to ensure bilosomes formation, elasticity, and spherical shape, respectively.Results: The resulting vesicles publicized EE from 56.21% to 94.21%, VS from 183.64 to 701.8 nm, PDI values oscillating between 0.33 and 0.53, ZP (absolute value) from 29 to 44.2 mV, biphasic release profile within 24 h from 60.62 and up to 75.28%, and permeation flux enhancement (198.79– 431.91 ng cm − 2 h− 1) in comparison with the non-formulated drug (154.26 ng cm − 2 h− 1). Optimized formulation was found to be F8 with EE = 79.49%, VS = 237.68 nm, ZP = 40.9 mV, PDI = 0.325, R = 75.28%, Jss = 333.45 ng cm− 2 h− 1 and DI = 6.5 with spherical self-closed non-aggregated vesicles and non-superimposed bands of its components in the FTIR.Conclusion: Overall results showed that bilosome incorporation of metformin HCL improved permeation and offered a new nano-carrier for active transdermal delivery.Graphical Abstract: Keywords: metformin HCL, bile salts, bilosome, Design-Expert 13, permeation study, edge activators

Objective: The present work represents a reverse-phase high-performance liquid chromatography method in addition to stability studies for sequential estimation of remogliflozin etabonate, vildagliptin, and metformin HCl in tablet formulation., Method: The mentioned method utilizes a Phenomenex Luna C18 column (250×4.6mm, 5μm). It consists of a column oven's temperature of 35°C. Mobile phase includes a mixture of 50% phosphate buffer (pH - 6.8) and 50% acetonitrile along with a flow rate of 0.8mL/min and 20minutes of run time. The injection volume was 20μL; 217nm is a detection wavelength, and a PDA detector is used for detection., Results: The suggested technique was proven and validated per the ICH Q2 (R1) guideline. The combination was put under stress conditions that included acid, base, thermal, photolytic, and oxidative degradation. The combination was considerably degraded under oxidative, acidic, and basic circumstances for deterioration, and the degradation results were accurately identified from the observed peaks, demonstrating the method's effectiveness in detecting stability., Conclusion: The technique was quick, precise, sensitive, and accurate; as a result, it may be used in quality control laboratories and the pharmaceutical industry for routine quality monitoring of tablets containing all three medications., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

A gastroretentive in situ oral gel containing metformin hydrochloride (Met HCl) was prepared based on sodium alginate (Sod ALG), calcium carbonate, and hydroxyethylcellulose (HEC). The optimal composition of the formulation was explored based on the design of experiments (DoE). First, a 32 full factorial design was used for formulation E1 to determine proper composition of Sod ALG and calcium carbonate. Second, a circumscribed central composite design was employed to add HEC as a thickening agent (formulation E2). The dissolution rates at 15, 30, 60, 120, and 240 min were used as responses. Partial least squares regression analysis indicated the effect of each component in delaying the release of Met HCl in the oral gel formulation. The optimized formulation E2-08 consisting of 1.88% Sod ALG, 0.63% HEC, and 1.00% calcium carbonate and two more formulations, E2-10 and E2-12 conformed to USP monograph for extended release. Other physicochemical properties, including floating lag time and duration, viscosity, and pH, measured for each batch and FT-IR spectrometry analysis showed no unexpected interaction between Met HCl and excipients. The current study suggests the potential use of a gastroretentive in situ oral gel for Met HCl helping patient compliance. This study highlights that a systematic approach based on DoE allows the formulation optimization. [ABSTRACT FROM AUTHOR]

Corneal neovascularization (CNV) is a serious ocular surface disease that causes the cornea to lose its transparent structure. It is a difficult disease to treat, so different drugs and different carrier systems are tried in the treatment of the disease. One of these methods is the combined application of metformin HCl (MHL) with a fluoroquinolone group antibiotic. The aim of this study is to load MHL with low permeability into a drug delivery system that can prolong the residence time on the ocular surface. In this context, different in situ gel formulations were produced by using poloxamer, a thermosensitive polymer, together with hydroxypropylmethylcellulose, a natural viscosity increaser. In situ gels were evaluated for clarity, pH, gelation temperature, and rheological behaviors and selected two formulation. After loading MHL and moxifloxacin HCl (MOX) into these two formulations, it was determined that they were clear, had a pH of around 7, a gelling temperature of 34-35 °C, and showed pseudoplastic flow. However, drug loading capacities were found to be over 97%.When in vitro release studies were examined, it was determined that both MHL and MOX released for at least six hours. The results showed that the combination of PF127 and HPMC has potential as an in situ gelling systems for ocular delivery of MHL and MOX. [ABSTRACT FROM AUTHOR]

Abstract Background Metabolic dysregulation is one of the hallmarks of tumor cell proliferation. Evidence indicates the potential role of the 5′adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B/Akt signaling pathway in regulating cell proliferation, survival, and apoptosis. The present study explores the effect of metformin HCl and the combination of α- and β-asarone on the proliferation of HepG2 cells in the presence of high glucose levels simulating the diabetic-hepatocellular carcinoma (HCC) condition. Results The metformin and asarone reduced HepG2 cell viability in a dose-dependent manner and induced morphological changes as indicated by methyl thiazolyl tetrazolium (MTT) assay. The metformin and asarone arrested the cells at the G0/G1 phase, upregulated the expression of AMPK, and downregulated Akt expression in high glucose conditions as identified by the flow cytometry technique. Further, the upregulated AMPK led to a decrease in the expression of phosphoenolpyruvate carboxykinase-2 (PCK-2) and sterol regulatory element-binding protein-1 (SREBP-1). Conclusion The anti-proliferative effect of metformin and asarone in the diabetic-HCC condition is mediated via AMPK and Akt pathway.

Abstract Background In the present study, an improved simple, specific, rapid, sensitive, precise, accurate and stability-indicating RP-HPLC method for the simultaneous estimation of ertugliflozin pidolate and metformin hydrochloride in bulk and tablets was developed and validated. The separation of ertugliflozin pidolate and metformin HCl was achieved isocratically on Kromasil C18 column (150 mm × 4.6 mm, 5 μm) using 0.1% ortho-phosphoric acid buffer (pH 2.7):acetonitrile (65:35% v/v) as mobile phase, pumped at a flow rate of 1 ml/min and column temperature of 30 ± 2 °C. HPLC grade water:ACN (1:1) was used as diluent. About 10 μl of standard solution of the drugs was injected, and the eluted analytes were detected at 224 nm. Results Metformin HCl was eluted at 2.170 min and ertugliflozin pidolate at 2.929 min with a run time of 5.0 min. Linearity of the developed method was observed in the concentration range of 0.9375–5.625 μg/ml for ertugliflozin pidolate and 62.5–375 μg/ml for metformin HCl with a correlation coefficient of 0.999 for both the drugs. LOD for ertugliflozin pidolate and metformin HCl were 0.025 μg/ml and 0.87 μg/ml respectively. LOQ for ertugliflozin pidolate and metformin HCl were 0.076 μg/ml and 2.63 μg/ml. Conclusion The developed RP-HPLC method for the simultaneous estimation of ertugliflozin pidolate and metformin HCl in bulk and tablets was simple, rapid, sensitive, accurate, precise, linear, and stability indicating. Hence, the developed method could be used for the routine quality control of the drugs in bulk and tablets.

Hydrogels are ideal biomaterials owing to their unique network structure that facilitates considerable hydrophilicity and biocompatibility. At the same time, hydrogels also possess soft physical properties when combined with living tissue. In this study, metformin hydrogen chloride (metformin HCl)-loaded stimuli-responsive poly(N-isopropylacrylamide) (pNIPAAm) –chitosan–polyvinyl alcohol (PVA) hydrogels were synthesized through a freezing and thawing procedure and subsequently subjected to gamma irradiation at room temperature. The gel content and the water absorption capacity of the synthesized hydrogels were analyzed. The polymer interaction in the matrix was observed by Fourier transform infrared spectroscopy, and the release of metformin HCl was studied in different pHs and temperatures. The hydrogels had 85% of the gel content and 373% of the water absorption capacity after 24 h of water immersion. The metformin HCl-loaded (pNIPAAm–chitosan–PVA) hydrogels demonstrated a sustained drug release profile over 7 h. The drug release exhibited pH-dependent and temperature-dependent behavior. The developed hydrogels showed good metformin HCl release ability at pH 3 and pH 6.86 at the temperature of 37oC. The results showed that pNIPAAm–chitosan–PVA hydrogels could be employed for controlled drug release of metformin HCl.

Purpose: The aim of this study was to evaluate the combined effect, acacia gum(AG)/ hydroxypropylmethylcellulose (HPMC), on biopharmaceutical performances of floating tablets of metformin hydrochloride (MTH) prepared by thermoplastic granulation using stearic acid. Methods: We have prepared the matrixes using AG/HPMC as a polymer combination. This combination of polymers which represents 15% of the total mass of tablet was used at various ratios 3:1, 1:1, 1:3, with two viscosity grade of HPMC (k15M and k100M). The developed matrixes have been evaluated for their pharmacotechnical and biopharmaceutical properties. Results: In addition to the satisfactory physical characteristics of matrixes, it was revealed that the Fc3 and Fc6 formulations with AG/HPMC k15M and AG/HPMC k100M respectively, at ratio, 1:3 were considered the most performance. These formulations have shown swelling, fast flotation, 360 and 480 seconds respectively, and remained floating on the surface of the medium for more than 24 hours, with the matrix integrity, while F1, containing only AG, did not show swelling and did not float. In addition, extended in vitro release (>8 hours) with decreased dissolved MTH rates was demonstrated for Fc3 and Fc6 matrixes, 95% and 91% respectively, compared to F1 where MTH dissolution was complete after 2 hours. The drug release from the highest-performance matrixes (Fc3 and Fc6) was found to follow Korsmeyer-Peppas’s model. The mechanism drug release was controlled by diffusion and erosion. Conclusion: The AG/HPMC combination was suitable as a polymer matrix to improve the in vitro biopharmaceutical properties of MTH compared to AG.

A selective and simple salting‐out‐assisted thin‐layer chromatographic methodology was developed for the simultaneous determination of two oral hypoglycemic drugs, dapagliflozin (DAPA) and metformin (MET) in their pure forms, tablets and spiked human plasma samples. Silica gel 60 F254 plates were used in the separation of the two drugs using a mobile phase consisting of 0.5 m (NH4)2SO4 and methanol (3:7, v/v). The plates were scanned in the reflectance mode at λmax = 237 nm. The obtained retardation factor (Rf) values for DAPA and MET were 0.77 ± 0.02 and 0.25 ± 0.02, respectively. The thin‐layer chromatography method was validated according to International Conference on Harmonization guidelines. The peak areas were linearly increased with the increases in concentrations of 45–1,000 and 50–1,500 ng/band for DAPA and MET, respectively. Moreover, the method was applied to estimate the molecular lipophilicity parameters of DAPA and MET via retention data. The suggested method was efficiently utilized for the analysis of DAPA and MET in pharmaceutical tablets and plasma samples with recoveries 98.4–100.4 and RSDs in the ranges of 1.4–2.6 and 2.2–3.0% for DAPA and MET, respectively. [ABSTRACT FROM AUTHOR]

The objective of the present work was to formulate and evaluate bilayer tablets of alogliptin and metformin HCl. Combining alogliptin with metformin HCL gives additional benefits in comparison with either drug alone and could be considered for patients whose quality of life is impaired by diabetes mellitus. The study was performed to design bilayer tablets of alogliptin immediate release layer and metformin HCl sustained release layer by wet granulation method. The immediate release layer comprised Crospovidone superdisintegrant and sustained release layer comprised HPMC K4M as rate release controlling polymers and PVPK30 was used as binder for both layers. The in vitro release of drug from the formulations was studied in 0.1N HCl acidic buffer and pH 6.8 phosphate buffer, and it was found that the prepared sustained release layer tablets were able to sustain the release of the drug up to 12 h and in vitro studies of alogliptin shown more than 80% of drug was released within 30 min. As per ICH guidelines, accelerated stability studies were carried out and results were found within the range. The release of alogliptin follows a zero order release model and the release of metformin HCl follows Higuchi model release. [ABSTRACT FROM AUTHOR]

A gastroretentive in situ oral gel containing metformin hydrochloride (Met HCl) was prepared based on sodium alginate (Sod ALG), calcium carbonate, and hydroxyethylcellulose (HEC). The optimal composition of the formulation was explored based on the design of experiments (DoE). First, a 32 full factorial design was used for formulation E1 to determine proper composition of Sod ALG and calcium carbonate. Second, a circumscribed central composite design was employed to add HEC as a thickening agent (formulation E2). The dissolution rates at 15, 30, 60, 120, and 240 min were used as responses. Partial least squares regression analysis indicated the effect of each component in delaying the release of Met HCl in the oral gel formulation. The optimized formulation E2-08 consisting of 1.88% Sod ALG, 0.63% HEC, and 1.00% calcium carbonate and two more formulations, E2-10 and E2-12 conformed to USP monograph for extended release. Other physicochemical properties, including floating lag time and duration, viscosity, and pH, measured for each batch and FT-IR spectrometry analysis showed no unexpected interaction between Met HCl and excipients. The current study suggests the potential use of a gastroretentive in situ oral gel for Met HCl helping patient compliance. This study highlights that a systematic approach based on DoE allows the formulation optimization.

Glimepiride is often combined with metformin HCl as an oral antidiabetic in type II diabetes mellitus, which provides a complementary and synergistic effect with multiple targets for insulin secretion. Glimepiride includes class II of BCS, which solubility practically insoluble in water but high permeability, which will impact the drug's small bioavailability. In contrast, metformin HCl includes class III of BCS, which has a high solubility in water, but low permeability is absorbed approximately 50-60% in the digestive tract given orally. The co-crystallization method can be used to improve the glimepiride solubility properties and the permeability properties of metformin HCl by interrupting glimepiride with metformin HCl physically. This study aims to identify the physical interactions between glimepiride and metformin HCL using a thermal analysis of Differential Scanning Calorimetry (DSC) and then confirmed by a computational approach. Identifying the physical interactions between glimepiride and metformin HCL was carried out by plotting the melting points generated from the endothermic peaks of the DSC thermogram at various compositions versus the mole ratios of the two were further confirmed by the computational approach using PatchDock. The results of the phase diagram analysis of the binary system between glimepiride and metformin HCl show a congruent pattern, which indicates the formation of co-crystal or molecular compounds at a 1 : 1 mole ratio at 228°C. Computational approach results showed that the interaction between glimepiride and metformin HCl did not form new compounds but heterosinton formation that was stable in molecular dynamics simulations.

A simple, specific, accurate, precise and stability-indicating RP-HPLC method was developed and validated for the simultaneous estimation of metformin HCl and canagliflozin in pharmaceutical formulation. The method was developed using the Altima C8 column (150 ×4.6 mm, 0.5 μm) with a mobile phase consisting of acetonitrile and 0.1 % orthophosphoric acid in water (62:38 %V/V) with a flow rate of 1 mL/min. Detection was carried out at 254 nm using a PDA detector. The retention time for metformin HCl and canagliflozin was found to be 2.282 and 3.339 min, respectively. The proposed method was validated for linearity, range, accuracy, precision, robustness, LOD and LOQ. Linearity was observed over a concentration range 15-225 μg/mL for metformin HCl (r² =0.9995) and 5-40 μg/mL for canagliflozin (r2 =0.9988). The % RSD for intraday and interday precision was found to be 0.13 and 0.20 for metformin HCl and 0.18 and 0.20 for canagliflozin. The LOD and LOQ were found to be 0.16 μg/mL and 0.54 μg/mL for metformin HCl and LOD and LOQ were found to be 0.05 and 0.21 μg/mL for canagliflozin. Metformin HCl and canagliflozin were subjected to stress conditions of degradation including acidic, alkaline, oxidative, thermal and photolysis. [ABSTRACT FROM AUTHOR]

The study proposes a solution to content uniformity problem of repaglinide-metformin HCl fixed dose tablet combination with optimization of particle size distribution and tapped density of repaglinide and metformin granules. The developed dosage forms contain less than 0.5% w/w repaglinide and more than 75% w/w metformin hydrochloride in the composition, resulting in content uniformity problems. A route for, minimizing susceptibility to segregation during the tablet press operation, thereby improving content uniformity, was studied through adjusting the particle size distribution and tapped density of the granules. In this study, a new specification in manufacturing method was developed for obtaining repaglinide and metformin granules with particle size distribution and tapped density properties optimized for tablet homogeneity. Specific particle size distribution and tapped density specifications between metformin HCl and repaglinide granules were described as (i) particle size distribution (D90, D50 and D10) of metformin HCl granule should be less than or equal to three times of particle size distribution (D90, D50 and D10) of repaglinide granule; and (ii) tapped density of metformin HCl granule should be less than or equal to two times of tapped density of repaglinide granule. Assay and in vitro dissolution rate analysis were performed by validated HPLC methods. [ABSTRACT FROM AUTHOR]

In twin screw melt granulation, granules are produced by passing mixtures of drug substances and polymeric binders through twin screw extruder such that temperatures are maintained below melting point of drugs but above glass transition of polymers used, whereby the polymers coat surfaces of drug particles and cause their agglomeration into granules. Since various formulation factors, such as binder type and concentration, and processing variables like extrusion temperature, screw configuration, and screw speed, can influence the granulation process, the present investigation was undertaken to study their effects on tabletability of granules produced. Three different types of polymeric binders, Klucel® EXF (hydroxypropyl cellulose), Eudragit® EPO (polyacrylate binder), and Soluplus® (polyvinyl caprolactam-co-vinyl acetate-ethylene glycol graft polymer), were used at 2, 5, and 10% concentrations. Metformin hydrochloride (HCl) (mp: 222°C) and acetaminophen (mp: 169°C) were used as model drugs, and drug-polymer mixtures with metformin HCl were extruded at 180, 160, and 130°C, while those with acetaminophen were extruded at 130 and 110°C. Other process variables included screw configurations: low, medium, and high shear for metformin HCl, and low and medium shear for acetaminophen; feed rates: 20 and 60 g/min; and screw speed of 100 and 300 RPM. Formulation and process variables had significant impact on tabletability. The target tensile strength of ≥2 MPa could be obtained with all polymers and at all processing temperatures when metformin HCl was granulated at 180°C and acetaminophen at 130°C. At other temperatures, the target tensile strength could be achieved at certain specific sets of processing conditions. [ABSTRACT FROM AUTHOR]

Background: In present work attempt has been made to develop and validate a simple and sensitive UV spectrophotometric method for simultaneous estimation of Telmisartan and Metformin Hydrochloride. Objectives: To develop simple, precise, robust, sensitive and accurate UV-Spectrophotometric method for the simultaneous estimation of Telmisartan and Metformin HCl and to formulate the combined tablet dosage formulation of Telmisartan and Metformin HCl respectively. Methods: The optimum condition for the analysis of the drug was established with Methanol as solvent. Maximum absorption wavelength were found to be 296nm and 237nm for Telmisartan and Metformin Hydrochloride. It showed linear response between the concentration ranges of 2-12µg/ml and 0.1-0.6 µg/ml for Telmisartan and Metformin Hydrochloide espectively. The linear regression coefficient was found to be 0.999. The method was validated for linearity, Precision, ruggedness, specificity, Sensitivity as per ICH guidelines and all the values of validation was found to be within the acceptance. Hence it can be concluded that method was new, simple, selective, specific, precise for simultaneous estimation of Telmisartan and Metformin Hydrochloride in bulk powder. [ABSTRACT FROM AUTHOR]

The poly(D,L-lactide-co-glycolide) (PLGA) based second-generation nanocrystals prepared by modified nanoprecipitation method, is the method of choice for encapsulation of both lipophilic and hydrophilic drugs. In this study, nanoprecipitation technique was adopted to develop second generation nanocrystals of PLGA loaded with metformin HCl (MHc). Poloxamer 188 with three different concentrations (0.5, 0.75, 1% w/v) in combination with PLGA at 1, 2, 3% concentrations (w/v) successfully produced MHc loaded PLGA second generation nanocrystals. The effects of poloxamer 188, amphiphilic triblock copolymer on carrier particle size, surface morphology, polydispersity index, zeta potential, drug entrapment efficiency and drug release of nanoformulation were investigated. The optimized formulation of second-generation nanocrystals with concentrations 0.75% w/v poloxamer 188 and 2% w/v PLGA, could produce particle size of 114.6 nm, entrapment efficiency of 63.48% and drug release 80.23% at 12 h. A blank formulation with the same composition as optimized formulation without addition of poloxamer188 compared with optimized formulation, exhibited nanoparticles of larger mean particle size of 212.9 nm with entrapment efficiency of 68.47% and 50.5% drug release at 12 h. Transmission electron microscopy (TEM) analysis of the nanoformulations revealed that poloxamer188 greatly contributed to smooth, spherical morphology of nanosize polymeric nanoparticles. Further Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies on nanoformulation emphasized the significance of poloxamer188 in formulation and development of optimized MHc loaded PLGA nanosuspensions of second generation nanocrystals. In conclusion, the study emphasizes that poloxamer 188 was a versatile excipient, which played a pivotal role in producing nanosize carrier with high drug release profile of MHc loaded PLGA nanosuspensions of second generation nanocrystals.

In this investigation, microcrystalline cellulose (MCC) was functionalized with metformin HCl using (3-chloropropyl)triethixysilane (CPTES) as a coupling agent. Polyethersulfone (PES) membranes were incorporated with different concentrations of modified MCC (MMCC) to enhance its affinity for heavy metals during filtration of aqueous solutions. The composite membranes were characterized via fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), atomic force microscopy (AFM), Brunauer–Emmett – Teller (BET) method, porosity and contact angle measurements and mechanical analysis. The presence of MMCC in the host matrix was confirmed by FTIR. Although composites decomposed at lower temperatures, their thermal stability was sufficient to meet their performance requirements. DSC showed enhanced glass transition temperature (T g) due to the interfacial interactions between membrane constituents which restrict the mobility of polymer chains. Microscopic imaging revealed higher surface roughness of composites compared to neat PES. Inclusion of MMCC increased the porosity and hydrophilicity of the membrane which consequently, higher permeability can be achieved. [ABSTRACT FROM AUTHOR]

Drug-drug cocrystals (DDC) represent a unique subset of pharmaceutical materials offering distinct advantages in combination therapies, pharmacokinetics, and patient compliance. However, their structure–function relationships are rarely reported despite its central importance in successful medicine. A material-sparing approach consisting of a molecular and structural perspective is reported to evaluate tabletability of a model DDC, metformin:salicylic acid, relative to its components: metformin HCl (MET) and sodium salicylate (SAL). MET alone displayed a very poor tabletability, which could be attributed to its isotropic and stiff interaction topology. SAL displayed a highly anisotropic interaction topology with layers of strongly hydrogen-bonded salicylate molecules promoting deformation and tabletability. This is also confirmed by its low moduli. DDC yielded intermediate stiffness and elastic anisotropy material with an improved plastic flow and overall better tabletability. Overall, DDC is a promising therapeutic class requiring the physical–mechanical evaluation to assure their processability to enjoy their therapeutic advantages. [ABSTRACT FROM AUTHOR]

This study investigates the fabrication, characterization and optimization of Linum usitatissimum mucilage (LSM) with sodium alginate mucoadhesive microspheres loaded metformin HCl, a sustained release dosage form prepared by ionic gelation technique. The effect of changing the polymer ratio with drug was studied for drug encapsulation efficiency and in vitro drug release for 12 h. Drug entrapment efficiency of all formulations was in the range of 77.93 ± 3.67 to 92.25 ± 4.08% with sustained release of 80 ± 0.12% to 88 ± 0.33% for 12 h. It followed Korsmeyers Peppas model (R2 = 0.9786–0.9964) with super case II transport mechanism. Average microsphere size of all formulations was within the range of 817–911 μm. SEM, FTIR were also characterized and swelling behavior of microspheres was affected by pH of buffer medium. These microspheres also showed good mucoadhesivity in wash off test. The optimized LSM-alginate mucoadhesive microspheres containing metformin HCl demonstrated significant hypoglycemic effect in alloxan-induced diabetic rats for prolonged period of time. Unlabelled Image [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the combined effect, acacia gum(AG)/ hydroxypropylmethylcellulose (HPMC), on biopharmaceutical performances of floating tablets of metformin hydrochloride (MTH) prepared by thermoplastic granulation using stearic acid. Methods: We have prepared the matrixes using AG/HPMC as a polymer combination. This combination of polymers which represents 15% of the total mass of tablet was used at various ratios 3:1, 1:1, 1:3, with two viscosity grade of HPMC (k15M and k100M). The developed matrixes have been evaluated for their pharmacotechnical and biopharmaceutical properties. Results: In addition to the satisfactory physical characteristics of matrixes, it was revealed that the Fc3 and Fc6 formulations with AG/HPMC k15M and AG/HPMC k100M respectively, at ratio, 1:3 were considered the most performance. These formulations have shown swelling, fast flotation, 360 and 480 seconds respectively, and remained floating on the surface of the medium for more than 24 hours, with the matrix integrity, while F1, containing only AG, did not show swelling and did not float. In addition, extended in vitro release (>8 hours) with decreased dissolved MTH rates was demonstrated for Fc3 and Fc6 matrixes, 95% and 91% respectively, compared to F1 where MTH dissolution was complete after 2 hours. The drug release from the highest-performance matrixes (Fc3 and Fc6) was found to follow Korsmeyer-Peppas's model. The mechanism drug release was controlled by diffusion and erosion. Conclusion: The AG/HPMC combination was suitable as a polymer matrix to improve the in vitro biopharmaceutical properties of MTH compared to AG. [ABSTRACT FROM AUTHOR]

Hydrogels are ideal biomaterials owing to their unique network structure that facilitates considerable hydrophilicity and biocompatibility. At the same time, hydrogels also possess soft physical properties when combined with living tissue. In this study, metformin hydrogen chloride (metformin HCl)-loaded stimuli-responsive poly(N-isopropylacrylamide) (pNIPAAm) --chitosan--polyvinyl alcohol (PVA) hydrogels were synthesized through a freezing and thawing procedure and subsequently subjected to gamma irradiation at room temperature. The gel content and the water absorption capacity of the synthesized hydrogels were analyzed. The polymer interaction in the matrix was observed by Fourier transform infrared spectroscopy, and the release of metformin HCl was studied in different pHs and temperatures. The hydrogels had 85% of the gel content and 373% of the water absorption capacity after 24 h of water immersion. The metformin HCl-loaded (pNIPAAm--chitosan--PVA) hydrogels demonstrated a sustained drug release profile over 7 h. The drug release exhibited pH-dependent and temperature-dependent behavior. The developed hydrogels showed good metformin HCl release ability at pH 3 and pH 6.86 at the temperature of 37oC. The results showed that pNIPAAm--chitosan--PVA hydrogels could be employed for controlled drug release of metformin HCl. [ABSTRACT FROM AUTHOR]

A sensitive, accurate, precise, and robust high-performance thin-layer chromatography (HPTLC) method has been developed for the simultaneous quantification of empagliflozin, linagliptin, and metformin HCl in bulk and synthetic mixture. The method applied HPTLC aluminum plates pre-coated with silica gel 60 F254 as the stationary phase along with n-butanol:water:glacial acetic acid (6:3:1, v/v) as the mobile phase. The Rf values of empagliflozin, linagliptin, and metformin HCl were found to be 0.73, 0.52, and 0.33, respectively. Densitometric analysis was carried out in the absorbance mode at 223 nm. The method was obtained linear in the range of 0.1–0.7 μg/band for empagliflozin, 0.05–0.35 μg/band for linagliptin, and 10–70 μg/band for metformin HCl, respectively. From synthetic mixture, the percentage (%) amounts of all three drugs were found to be more than 98% by the proposed HPTLC method. The method was validated as per the International Conference on Harmonisation (ICH) guideline Q2(R1). [ABSTRACT FROM AUTHOR]

Doxorubicin and Metformin HCL is a known chemotherapeutic combination that wipes out tumors and prevents their recurrence. However, limited site specificity confines its application. Here we report Doxorubicin and Metformin HCL–loaded guar gum micro-particles prepared by emulsification cum-solidification method. Developed micro-particles were characterized as spherical shape particles with smooth surface and micro size diameter. Encapsulation of drugs in combination was confirmed by their characteristic functional groups (FT-IR), change in phase transition temperature (DSC) and X-ray diffraction pattern (XRD). Particles were observed to be stable at 25 and 5°C. The in vitro Doxorubicin and Metformin HCL release study in simulated gastric (SGF), intestinal (SIF) and colonic fluid (SCF) confirms restricted release in SGF (9.3 and 9.6%, respectively, in 2 h) and SIF (10.8 and 14.7%, respectively, in the next 3 h) and highest release in SCF (about 68 and 73.3%, respectively) in colon. Developed micro-particles showed 78% recovery in tumor volume and considerable improvement in histological changes. X-ray images confirmed good target ability of micro-particles to colon. In conclusion, the specially designed, stable micro-particles are able to target drug combination to colon and improve efficacy by ensuring maximum drug release in colon as compared with Doxorubicin and Metformin HCL combination. [ABSTRACT FROM AUTHOR]

A sustained-release non-effervescent floating matrix tablet was prepared using a simple and efficient direct compression of spray-dried granules containing metformin hydrochloride and cetyl alcohol with hydroxypropyl methylcellulose K15M (HPMC K15M). The design of experiments was employed to explore the optimal composition of the tablet. The similarity factor was employed to evaluate the equivalence in dissolution profiles between the test tablets and Glucophage XR as a reference. Bootstrap analysis was used to eliminate the formulations for which the dissolution profile was potentially inequivalent to that of the reference. The optimized tablet consisting of 150 mg of cetyl alcohol and 17% HPMC K15M showed a dissolution profile comparable with that of the reference with a similarity factor of 52.41, exhibited a floating lag time of less than 3 s in buffer media, remained floating for 24 h, and reduced the tablet weight by about 20% compared to that of the reference. The current study sheds light on the potential use of non-effervescent gastro-retentive extended-release tablets for high-dose drugs using a simple and efficient direct compression method, and as a potential alternative treatment for Glucophage XR. This study also highlights the importance of a systematic approach to formulation optimization and the evaluation of the dissolution profile.

Niosomes as drug delivery systems have the ability to decrease drugs' side effects and increase their therapeutic effectiveness. Metformin HCl is an oral antihyperglycemic agent belonging to biguanides. It is the most commonly chosen drug as a startup therapy for patients newly diagnosed with type 2 diabetes. This study aims to encapsulate metformin HCl inside niosomes to be used as a transdermal formulation helping to prolong its antidiabetic effect and investigate its ability to enhance wound healing in diabetic patients. Thin film hydration method was used to prepare metformin HCl niosomes using different proportions of Span 60, Span 40, Tween 80, and cholesterol. All formulations were characterized using transmission electron microscope, zeta potential, and vesicle size. In vitro release studies, stability studies and in vivo evaluation were conducted on selected niosomal formulations. The results of entrapment efficiency ranged from 13% to 32%. Vesicle sizes were determined in nano-range. The in vitro release profile of metformin HCl from niosomes occurred in two consecutive phases. Biological evaluation on diabetic rats revealed that metformin HCl niosomal gel given every 2 days showed a better sustained antidiabetic effect than oral doses given daily. It also showed an improvement in wound healing for diabetic rats given metformin formulations compared to nontreated ones. [ABSTRACT FROM AUTHOR]

The evidence suggests that the hyperglycemia and hyperinsulinemia of diabetes mellitus (DM) are risk factors for the development of hepatocellular carcinoma (HCC). The aim of the present study was to examine the effect of streptozotocin (STZ)-induced DM on promoting diethylnitrosamine (DEN) induced HCC in male wistar rats. Further, we investigated the administration of (α)-and (β)-asarone and metformin HCl on experimentally induced diabetic-hepatocellular carcinoma. Diabetes was induced by single dose of STZ (55 mg/2 ml/kg b.w. i.p.) and HCC by single dose of DEN (200 mg/ml/kg b.w. i.p.). Another group received the STZ followed by DEN two weeks later to mimic diabetic-HCC. The combined dose of (α)-and (β)-asarone (50 μg/1.5 ml/kg b.w. p.o. in the ratio of 1:1) and metformin HCl (250 mg/1.5 ml/kg b.w. p.o.) treatment was compared with the STZ + DEN group. The blood and liver samples were collected at the end of 12 and 18-weeks to study biochemical and histopathological changes in liver. The STZ induced diabetes promoted the tumor progression due to administration of DEN. The treatment of asarones and metformin significantly reduced the levels of glucose, glycosylated hemoglobin, liver dysfunction markers and tumor biomarkers along with an increase in level of insulin when compared to diabetic-HCC group. Histopathological examination indicated that asarones and metformin attenuate the inflammation, fibrosis, cirrhosis and development of spontaneous HCC. The STZ can be used to promote the DEN induced HCC. Treatment with (α)-and (β)-asarone attenuates the effect of STZ + DEN induced HCC akin to metformin. Unlabelled Image [ABSTRACT FROM AUTHOR]

To improve the heavy metal adsorption of microcrystalline cellulose (MCC), two successive grafting reactions of silylation by (3-chloropropyl)triethoxysilane (CPTES) and amine-functionalization with metformin HCl were performed and the modified MCC from the first and second steps were denoted as MMCC-1 and MMCC-2, respectively. MMCCs were characterized by fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA) and compared to MCC. The presence of the amine group on the MMCC-2 surface was confirmed by FT-IR analysis. According to the XRD results, the crystallinity index (CI) of MMCC-1 increased very slightly compared to that of MCC that can be attributed to the partial hydrolysis of amorphous parts because of acidic conditions used for MCC silylation but CI of MMCC-2 decreased due to the high temperature and long time in the 2nd step of modification. TGA revealed the lower thermal stability of MMCC-2 than the corresponding MCC. [ABSTRACT FROM AUTHOR]