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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]

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]

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]

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]

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 new smart simple validated spectrophotometric method was developed for the determination of two drugs one of which is in a very low concentration compared to the other. The method is based on spiking and dilution then simple mathematical manipulation of the absorbance spectra. This method was applied for the determination of a binary mixture of vildagliptin and metformin hydrochloride in the ratio 50:850 in laboratory prepared mixtures containing both drugs in this ratio and in pharmaceutical dosage form with good recoveries. The developed method was validated according to ICH guidelines and can be used for routine quality control testing. [ABSTRACT FROM AUTHOR]

The objective of this study was to prepare and characterize beads of Gelucire 43/01 for floating delivery of metformin hydrochloride (MH). The beads were evaluated for particle size, surface morphology, percent drug entrapment, percent yield, differential scanning calorimetry (DSC), in vitro floating ability, and in vitro drug release. Aging effect on storage was evaluated using hot stage microscopy (HSM), DSC, scanning electron microscopy, and in vitro floating ability. The formed beads were sufficiently hard and spherical in shape. Photomicrographs show that the surface was porous in nature. The average particle diameter of beads was found to be in the size range of 3.85 to 3.95 mm, and percent entrapment was 83.07% to 86.13%. The beads demonstrated favorable in vitro floating ability. The analysis of DSC thermograms revealed no physical interaction between the lipid and the drug in the prepared beads. Prepared formulations showed better controlled release behavior when compared with its conventional dosage form and comparable release profile with marketed sustained release product. HSM photomicrograph showed presence of some unmelted portion even at 43°C and completely melts on 51°C in aged sample. It was found that there was no significant effect on floating ability of aged beads since it remains floats up to 8 h study period. Thus, it is concluded that beads of Gelucire 43/01 could be serve as an effective carrier for highly water-soluble antihyperglycemic drugs like MH for the controlled delivery. [ABSTRACT FROM AUTHOR]