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Aim: A validated RP-HPLC method was established for the quantification of Amlodipine and Metoprolol succinate according to ICH guidelines. Materials and Methods: This method utilized a Phenomenex (US) C18 column with dimensions of 250X4.6 mm I.D and a particle size of 5 µm. Employing an isocratic elution technique, the mobile phase comprised pH 3.0 phosphate buffer solution and acetonitrile. Detection occurred at a wavelength of 215 nm and a flow rate of 1 mL/min was chosen to ensure optimal resolution for Amlodipine and Metoprolol succinate. Results and Discussion: Retention times were noted at 3.137 min and 5.672 min for Amlodipine and Metoprolol succinate, respectively. High correlation coefficients were achieved (0.9995 for Amlodipine and 0.9996 for Metoprolol succinate). The method exhibited precision, with low relative standard deviations of 0.357% for Amlodipine and 0.077% for Metoprolol succinate. In summary, the RP-HPLC method developed was specific, linear, precise and robust. Conclusion: The devised method was validated in terms of accuracy, precision, linearity, specificity, robustness and ruggedness. All formulations' sample recoveries were in good accordance with the claims made on their labels. [ABSTRACT FROM AUTHOR]

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The analytical community prioritizes adopting green techniques due to concerns over the environmental impact of chemical research. This study employs an integrated experimental strategy, combining the concept of design of experiment (DOE) and green analytical chemistry (GAC), to establish a robust, green RP-HPLC approach for the simultaneous estimation Cilnidipine (CIL) and Metoprolol succinate (MET). For method optimization, a central composite design (CCD) was implemented. Separation utilized Inertsil ODS 3 column (250 mm x 4.6 mm, 5 μm), with gradient mobile phase (ethanol: 17.65% at 0 min, 75.5% at 3 min) and phosphate buffer, flowing at 1 ml/ min. Detection wavelength at 230 nm. Column temperature (35±1°C), and injection volume 5 μL. Retention times: MET (4.672 min), CIL (7.457 min). The linearity was established over the range of 7-13 μg/ml for CIL and 35-65 μg/ml for MET. The values obtained for LOD and LOQ are 0.819 and 2.482 μg/ml (CIL) respectively, 3.875 and 11.743 μg/ml (MET). As per ICH Q14, the technique has been validated. Finally the green nature was examined by GAPI, AES and AGREE. Method found to be ecofriendly, simple and robust for simultaneous CIL and MET estimation in pharmaceutical formulations, easily adaptable for routine analysis. [ABSTRACT FROM AUTHOR]

Azelnidipine is a novel dihydropyridine calcium channel antagonist and Metoprolol succinate is a beta blocker, this combination was approved by CDSCO for Phase III clinical trial in April 2021. This combination is utilized to achieve a better outcome in the treatment of stage 2 hypertension. The present research includes an HPLC and Absorbance Correction UV method for the determination in synthetic mixture.The HPLC chromatography was performed using a gradient technique on a reversed-phase C18 column with mobile phase based and optimized depending on the polarity of the molecules. The Unesphere C18 column Agela Tech., (250 mm x 4.6 mm i.d, 5 μm,) as stationary phase and Acetonitrile: Phosphate Buffer pH 3.5 (40:60%v/v) as mobile phase with UV detection at 275 nm at 1 ml/min for gradient elution was used to achieve chromatographic separation over the linearity 10.0 - 30.0 μg/mL and 50.0–150.0 μg/mL with r2 0.9995 and 0.9993 for Azelnidipine and Metoprolol succinate respectively. The retention time was found to be 6.367 and 2.308 min for Azelnidipine and Metoprolol succinate respectively.% RSD of intraday precision of AZL and MET was found to be 0.01 – 0.03% and 0.01 – 0.03%, respectively. Interday presion was found to be 0.02 – 0.06% and 0.02 – 0.05%, respectively which are indicated that the method is precise.% recovery for AZL and MET by this method was found in the range of 99.85 - 100.76% and 99.23 - 99.89%, respectively. The system suitability test parameters theoretical plates were found to be 7042.56 (AZL) and 2231.74 (MET) and tailing factor was found to be 1.47 (AZL) and 1.52 (MET).The Absorbance Correction UV method was developed validated at 313 nm (λmax of Azelnidipine) and 275.40 nm (λmax of Metoprolol succinate) in methanol: distilled water (20:80, v/v) for estimation of AZL and MET respectively and show linearity 5.0 - 25.0 μg/mL and 25.0 - 125.0 μg/mL with r2 0.9998 and 0.9991 for Azelnidipine and Metoprolol succinate respectively.% RSD of intraday precision of AZL and MET was found to be 0.46 – 0.64% and 0.42 – 0.71%, respectively and for interday precision was found to be 0.40 – 0.65% and 0.22 – 0.75%, respectively.% recovery for AZL and MET by this method was found in the range of 100.50 - 100.77% and 100.30 - 100.78%, respectively. The value of% RSD within the limit indicated that the method is accurate and% recovery shows that there is no interference from the excipients.Both methods were validated as per ICH Q2(R1) guidelines. The analytical method validation parameters were found to be as per acceptance criteria. In terms of accuracy and precision, statistical testing employing an analysis of variance test did not find any significant differences between the two methods. The ICH Q2R1 recommendations extensive statistical validation of the two established methodologies, proving their effective use in the simultaneous study of the two medications in bulk and tablets made within the laboratory.The Analytical eco scale (AES), National environmental method index (NEMI), Green analytical procedure index (GAPI), and software-based Analytical greenness metric (AGREE) tools were used to assess the ecological impact of the new UV spectrophotometric technique and HPLC method. This assessment confirmed the method's environmental friendliness in terms of solvent usage, chemical compounds, energy consumption, and trash creation. Both methods can be used to successfully analyze Azelnidipine and Metoprolol succinate in combination dose form without interference from excipients. There were no spectral or chromatographic interferences from formulation excipients discovered. Because the proposed procedures are simple, quick, precise, and accurate, they were effectively used to determine Azelnidipine and Metoprolol succinate in their dose forms. To evaluate the greenness and whiteness of an analytical method, a reliable assessment of the health and environmental risk associated with chemical use is essential. An objective and useful way of risk assessment should consider all pertinent characteristics of substances utilized, the actual quantities required for method implementation, and the result of the assessment should be quantified using a standard unit.

The aim of this study is to design and evaluate metoprolol succinate sustained release (SR) matrix tablets employing a natural gum blend as the rate-retarder. Developing a tablet matrix utilizing locust bean gum (LBG), xanthan gum (XG), and guar gum (GG) was done to aid metoprolol succinate release over a 24-h period and help in once-daily dosage, reducing nocturnal episodes in hypertensive patients. In an effort to create a synergistic effect, attempts were made to combine commonly used natural gums, XG and GG, with LBG, which served as the primary release-retardant. The optimal way to formulate the tablet was studied using polymer blend ratios of 1:1, 1:3, 1:5, 1:1:1, 1:2:1 and 1.5:1.5:1. The same created polymer mix was used as the binding agent to prepare tablets utilizing the wet granulation process. Weight, thickness, hardness, content homogeneity, in-vitro drug release, erosion, and water uptake were used to characterize the formulations. Additional testing for drug-excipient compatibility was conducted. It was discovered that an XG:LBG:GG ratio of 1:2:1 produced the best outcomes having the highest t75% of cumulative drug release of 15.2 h, outperforming commercial formulations. A relation between the gum concentration and release rate retarding effect was also established. 3.33% of gum concentration showed optimal sustained release effects. The results concluded that the prepared SR metoprolol succinate tablets might be one of the best formulation for hypertensive patients that not only serves therapeutic purpose but also values the patients concern of providing minimal side-effect in the long run use of the medication. [ABSTRACT FROM AUTHOR]

A new simple, precise, accurate and selective stability indicating RP-HPLC method has been developed and validated for estimation of Metoprolol succinate and Azelnidipine in synthetic mixture. The method was carried out on Hypersil ODS C18 5µ column (250 x 4.6 mm) with a mobile phase consisting of Acetonitrile: 0.025 M KH2PO4 Buffer (70:30 v/v, pH adjusted to 3 with 10% Ortho phosphoric acid and flow rate of 1 mL/min. Detection was carried out at 228 nm. The retention time for Metoprolol succinate and Azelnidipine was found to be 3.281 min and 10.799 min, respectively. The Metoprolol succinate and Azelnidipine followed linearity in the concentration range of 25-125 µg/mL (r2= 0.9995) and 8-40 µg/mL (r2=0.9997) . The developed method was validated for linearity and range, accuracy, precision, and assay. Metoprolol Succinate and Azelnidipine was subjected to acid and alkali hydrolysis, oxidation and thermal degradation. This indicates that the drug is susceptible to acid, base, oxidation and thermal conditions. The degraded product was well resolved from the pure drug with significantly different Retention Time. The proposed method can be used for routine analysis of Metoprolol Succinate and Azelnidipine in synthetic mixture. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of metoprolol succinate (MET) plus trimetazidine (TMZ) in the management of angina pectoris in coronary artery disease. Methods: A total of 94 patients with coronary angina were assigned equally to study group (received MET plus TMZ in addition to conventional symptomatic treatment) and control group (received conventional symptomatic treatment such as statins, nitrates, and aspirin). Heart rate was measured by a pulse oximeter, while angina attacks were measured by electrocardiogram (ECG). Left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), and left ventricular posterior wall end diastole (LVPWD) were measured by cardiac ultrasound. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of hypersensitive C-reactive protein (hs-CRP). Adverse reactions were self-reported. Results: MET plus TMZ group produced significantly higher treatment responses for patients (95.74 %) than control group which received conventional medication (80.85 %, p < 0.05). Patients exhibited a significantly lower heart rate, fewer angina attacks, and a shorter duration of attacks after administration of MET plus TMZ compared to conventional medication (p < 0.05). MET plus TMZ treatment resulted in significantly higher LVEF, shorter LVEDD, and LVPWD than conventional treatment (p < 0.05). The study group exhibited a significantly milder inflammatory response indicated by lower serum hypersensitive C-reactive protein (hs-CRP) concentrations, and lower incidence of adverse events (4.26 %) compared to control group (17.02 %, p < 0.05). Conclusion: MET plus TMZ provides significant treatment benefits for patients with angina pectoris in coronary artery disease, mitigates clinical symptoms and inflammatory responses, enhances cardiac function, and improves treatment safety by reducing risk of adverse events. [ABSTRACT FROM AUTHOR]

Current research paper describes the RP-HPLC method for the determination of Azelnidipine and Metoprolol Succinate from the synthetic mixture. Azelnidipine is a Calcium channel blocker and Metoprolol Succinate is a Beta blocker. Both drugs are from the Anti-Hypertensive class. The present analytical method was developed on Shimadzu HPLC LC2010 which includes a UV-VIS detector and binary gradient system. Separation of the component was achieved on Hibar ODS C18 5 µ column (250 x 4.6 mm) at ambient temperature in isocratic mode with a mixture of Methanol: water (70:30 v/v) as mobile phase (pH - 3.0) at a flow rate of 1.0 ml/min with UV detection at 230 nm. The method shows a linear response in the range of 8-40 µg/ml of Azelnidipine and 25-125 µg/ml of Metoprolol Succinate. The devised approach was successfully used to determine azelnidipine and metoprolol succinate from a synthetic combination and was verified in following ICH Q2 R1 requirements. [ABSTRACT FROM AUTHOR]

Metoprolol succinate, a β-selective adrenergic blocker, has a short half-life, low bioavailability, and high dosing frequency. In-situ gel drug delivery is a good approach to achieve sustained release for once-daily administration that will prolong drug retention time at the stomach and increase absorption. Thus, the aim of the study is to formulate floating in-situ gel formulations of metoprolol succinate using Khaya gum (Khayasenegalensis, family Meliaceae) as a polymer. Khaya gum was characterized and used in formulating in situ gels of metoprolol succinate in comparison with Hydroxyl Propyl Methyl Cellulose (HPMC K15M) and Xanthan gum. The in-situ gel formulations were characterized for appearance, swelling, in-vitro buoyancy and in-vitro drug release. FTIR revealed major peaks characteristic of the gum. Khaya gum showed high swelling and good flow properties. In-situ gel formulations of metoprolol succinate containing Khaya were light brown with near neutral pH, higher swelling and a total floating time >24 h, comparable to those containing HPMC and Xanthan gums. Dissolution time t80 was 60.50 to >240 min with ranking Khaya

Backgroundβ-blockers have been recommended for patients with heart failure (HF) and atrial fibrillation (AF), but studies have shown that β-blockers do not reduce all-cause mortality or cardiovascular mortality in patients with HF and AF.ObjectiveTo investigate the difference in efficacy between oral amiodarone and metoprolol succinate for patients with HF with reduced ejection fraction (HFrEF) and persistent atrial fibrillation (pAF) with rapid ventricular response (RVR).MethodsPatients with HFrEF complicated with pAF with RVR treated in the People's Hospital of Chongqing Hechuan between March 2018 and March 2019 were enrolled in this prospective observational study. The primary outcomes were cardiovascular mortality and the first hospitalization for HF rate. The secondary outcomes were type B pro-brain natriuretic peptide (NT-proBNP) before/after treatment, left ventricular ejection fraction (LVEF) before/after treatment, average heart rate (AhR), and the rate of sinus rhythm after 1 year of follow-up.ResultsA total of 242 patients with HFrEF complicated with pAF with RVR were enrolled and divided into amiodarone + perindopril + spironolactone+ routine drug (amiodarone group, n = 121) and metoprolol succinate + perindopril + spironolactone +routine drug (metoprolol succinate group, n = 121) according to their treatment strategy. Cardiovascular mortality (4.9 vs. 12.4%, HR: 2.500, 95%CI: 1.002–6.237, P = 0.040) and first hospitalization for HF (52.9 vs. 67.8%, HR: 1.281, 95%CI: 1.033–1.589, P = 0.024) were significantly lower in the amiodarone group than in the metoprolol group. The mean ventricular rate in the amiodarone group was significantly lower than in the metoprolol group (64.5 ± 3.2 vs. 72.4 ± 4.2, P < 0.001). After 1 year of follow-up, the sinus rhythm rate was significantly higher in the amiodarone group than in the metoprolol group (38.8 vs. 7.4%, HR: 0.191, 95%CI: 0.098–0.374, P < 0.001). The difference in proBNP (3,914.88 vs. 2,558.07, P < 0.001) and LVEF (−6.89 vs. −0.98, P < 0.001) before and after treatment was significantly higher in the amiodarone group than in the metoprolol group.ConclusionIn conclusion, in this prospective observational study, the amiodarone group had lower risk of cardiovascular death and the first hospitalization for HF than metoprolol in HFrEF and persistent atrial fibrillation (pAF) with RVR. The mechanism may be related to improved cardiac function, rhythm control and ventricular rate control.Registration numberChiCTR2200057816; Registered 7 March 2022–Retrospectively registered: http://www.medresman.org.cn/pub/cn/proj/projectshshow.aspx?proj=4222.

The present investigation was computational predictability of Polyethylene Glycol (PEG) encapsulated modified release multiple unit pellets system (MUPS) tablet of Metoprolol succinate by quality by design (QbD). Quality target product profile (QTPP) and critical quality attributes (CQAs) of MUPS tablets were defined. Risk assessment was done using Ishikawa diagram and failure mode effect analysis (FMEA) as per ICH Q8 guidelines. Formulation was screened and optimized using Plackett–Burman and Box– Behnken design. Pellets were prepared by wruster coating system-using polymers such as hydroxypropyl methylcellulose (HPMC), Ethyl cellulose (EC) with other excipients. Formulation variables X1: HPMC and X2: EC have affected the drug release (Y1). PEG capsulation ensures the intactness of film after compression. ANOVA results confirm the selected model was statistically significant. This investigation demonstrated the PEG encapsulated HPMC and EC polymer coated with optimised curing time will achieve a single dose of metoprolol succinate applying QbD. [ABSTRACT FROM AUTHOR]

This study aimed to produce a gastroretentive floating tablet of Metoprolol succinate and examine the effects of release retardant on in vitro drug release. Metoprolol succinate is a ß1 selective antagonist used as an Anti-hypertensive, Antiarrhythmic, and Anti Angina. Metoprolol succinate has 48% oral bioavailability due to limited absorption from the lower gastrointestinal tract. The Metoprolol succinate floating tablets were designed to increase stomach retention, prolong drug release, and enhance drug bioavailability. To shorten the floating lag time, hydrophilic polymers like Hydroxypropyl methyl cellulose (HPMC K4M, K15M, and K100M), polyethylene oxide (PEO 303), and sodium bicarbonate as a gas-producing agent were incorporated into the formulation of the floating tablets. Different batches of Metoprolol succinate floating tablets were prepared by direct compression. All the formulations were evaluated for various quality control tests, such as weight variation, hardness, friability, swelling index, floating lag time, and total floating time. As a dissolution medium, 0.1 N HCl was used to conduct an in vitro release investigation on the tablets. The present study demonstrates the potential of the sustained-release floating tablets of Metoprolol succinate as an alternative to conventional formulations. [ABSTRACT FROM AUTHOR]

The present research was aimed to develop Metoprolol succinate sustained-release tablet by wet granulation using novel polymersEulophia herbacae and Remusatia vivipara tuber mucilage as release retardants. The formulations were prepared using a 32 full factorial design. In the current research, two factors were tested each at three levels. The concentration of Eulophia herbacea mucilage (X1) and Remusatia vivipara mucilage (X2) were selected as independent variables, and swelling index, t75 of % cumulative drug release, and drug content were selected as dependent variables. The prepared tablets were evaluated by weight variation test, hardness, friability, swelling index, drug release, and drug content. The optimized tablet was compared with reference formulation PROLOMET XL 100. The drug release kinetics study was performed by various models. It reveals that formulation follows anomalous diffusion (non-fickian) pattern and follows both diffusion-controlled and swelling controlled mechanisms of drug release. [ABSTRACT FROM AUTHOR]

The present study shows the compilation of the results obtained for a very simple, fast and precise highperformance thin-layer chromatography (HPTLC) - densitometric determination of chlorthalidone (CHL), metoprolol succinate (MET) and telmisartan (TEL) in bulk drugs as well as the commercially available formulation. The chromatographic separation of samples was performed on Silica Gel 60 F254 aluminum sheets using Toluene: Methanol: Ethyl acetate: Tri-ethylamine as the mobile phase in the volume ratio 4:0.8:1: 1.2. The densitometric scanning was performed at 225 nm wavelength using CAMAG TLC Scanner-IV. The mentioned chromatographic system showed the compact band and symmetrical peaks of CHL, MET and TEL with 0.40 (±0.2), 0.69 (±0.2) and 0.27 (±0.2) retardation factor (Rf) respectively. The reported method is linear in the concentration range of 500-2000 ng/band, 1000-4000 ng/band and 1600-6400 ng/band while the recovery was found in the range of 98.94-99.62%, 98.26-98.41% and 99.86-100.28% for CHL, MET and TEL respectively. The method assayed the marketed formulation with 99.89 (±0.91) for CHL, 98.92 (±1.07) for MET and 100.12 (±0.65) for TEL concerning the label claim. All the results suggested the agreement of the developed method to the ICH Q2(R1) guidelines and its applicability for day-to-day analysis of these drugs in combined pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Controlled release dosage forms maintain regulated pharmacokinetic profile of drug substance within its therapeutic window by ensuring constant plasma concentrations. Controlled release formulations not only increase the therapeutic efficacy of drug substances but also reduce their dose-related side effects. Present investigation was conducted to develop, optimize, and validate compressed coated controlled release tablet formulation for highly water-soluble drug substances which have no rate-controlling factor towards its release from dosage form. Drug dispersed waxy core tablet, press coated within the swellable hydrophilic polymeric barrier layer, was developed and optimized via quality by design approach (QbD) using Box-Behnken design. The optimized formulation was characterized and validated using in vitro quality control parameters. Attributes identified under SUPAC guidelines, such as drug release rates at 30 min, 6 h, and 12 h, were considered as the critical quality attributes (CQAs) that significantly affected efficiency of the compressed coated controlled release tablets. CQAs screened using risk assessment and Pareto chart analyses were used for optimizing controlled release dosage form. Findings revealed that tablets containing drug to wax ratio of 1:1, hydrophilic swellable polymer concentration of 200 mg, and prepared using compression pressure of 6.5 kg/cm2 exhibited the highest desirability indices in terms of controlling the release rate of drug substance. Optimized formulation was also evaluated for swelling rate, erosion rate, and other post-compression parameters, including release kinetics. Fickian diffusion-based zero-order controlled release of BCS class I drug substance was achieved through the developed dosage form. [ABSTRACT FROM AUTHOR]

The development of extended-release dosage forms with adequate drug release is a challenge for pharmaceutical companies, mainly when the drug presents high solubility, as in Biopharmaceutics Classification System (BCS) class I. This study aimed to develop extended-release mini-tablets containing metoprolol succinate (MS), while integrating design of experiments (DOE) and physiologically based biopharmaceutics modeling (PBBM), to predict its absorption and to run virtual bioequivalence (VBE) studies in both fasted and fed states. Core mini-tablet formulations (F1, F2, and F3) were prepared by direct compression and coated using nine coating formulations planned using DOE, while varying the percentages of the controlled-release and the pore-forming polymers. The coated mini-tablets were submitted to a dissolution test; additional formulations were prepared that were optimized by simulating the dissolution profiles, and the best one was submitted to VBE studies using GastroPlus® software. An optimized formulation (FO) containing a mixture of immediate and extended-release mini-tablets showed to be bioequivalent to the reference drug product containing MS when running VBE studies in both fasted and fed states. The integration of DOE and PBBM showed to be an interesting approach in the development of extended-release mini-tablet formulation containing MS, and can be used to rationalize the development of dosage forms. [ABSTRACT FROM AUTHOR]

Ranolazine being Na+ channel blocker agent, decreases the chances of angina attacks. Metoprolol exerts specific ß1 blocking effect which results into decreased cardiac contractility and heart Rate (1). Ultimately reduces oxygen demand of heart. Metoprolol enhances the pharmacological activity of Ranolazine so the combination gives better therapeutic activity (2). There is no UV visible method present for the simultaneous estimation of Ranolazine and Metoprolol. To formulate and evaluate such a formulation involving mentioned drugs this simultaneous equation method was developed using 0.1 N HCl as a solvent. Chosen wavelengths were 272 nm and 242 nm for Ranolazine and Metoprolol Succinate respectively. Linearity range was seen to be 7.5 to 40 ppm for Ranolazine and 1 to 5 ppm for Metoprolol. Recovery studies and Validation were successfully performed according to ICH guidelines. This method can be applied for any formulation consisting mentioned drugs without interference of other excipients. [ABSTRACT FROM AUTHOR]

A method for determining the concentration of coloured compounds in a solution is colorimetry. The intensity of the colour is related to the chemical concentration being measured. Because of its low cost and ability to collect, store, and interpret data all in one device, smartphone-based colorimetry has increased in appeal as an analytical tool. The camera on the phone is used as a detector in smartphone colorimetry. Both the smartphone colorimetric method and the UV method relied on the detection of colour intensity as concentration rose. The ammonium metavanadate reagent is orange red in colour, but when it reacts with Metoprolol succinate, it changes to a green colour complex. The developed method has good linearity in the 20-40µg/ml range. The colour intensity increases as the concentration of API increases. All of the photos were captured on a smartphone and analyzed with photometrix PRO software. The photometrix PRO application turns an image to an RGB histogram, and it also includes regression models. LOD and LOQ value for UV visible spectrophotometry technique is 1.05µg/ml and 3.189µg/ml, respectively. Photometrix PRO LOD and LOQ are 0.0338µg/ml and 0.102µg/ml, respectively. The percent RSD of Metoprolol succinate was <2% utilizing Photometrix PRO and UV method. The results of a statistical tool called a two-paired test on both procedures show that they are both equally significant. [ABSTRACT FROM AUTHOR]

Background: Cardiac graft denervation causes inadequate sinus tachycardia in patients after heart transplantation (HTX) which is associated with reduced survival. This study investigated the 5-year results of heart rate control with ivabradine or metoprolol succinate in patients after HTX. Methods: This registry study analyzed 104 patients receiving either ivabradine (n = 50) or metoprolol succinate (n = 54) within 5 years after HTX. Analysis included patient characteristics, medication, echocardiographic features, cardiac catheterization data, cardiac biomarkers, heart rates, and post-transplant survival including causes of death. Results: Demographics and post-transplant medication revealed no significant differences except for ivabradine and metoprolol succinate use. At 5-year follow-up, patients with ivabradine had a significantly lower heart rate (73.3 bpm) compared to baseline (88.6 bpm; P < 0.01) and to metoprolol succinate (80.4 bpm; P < 0.01), a reduced left ventricular mass (154.8 g) compared to baseline (179.5 g; P < 0.01) and to metoprolol succinate (177.3 g; P < 0.01), a lower left ventricular end-diastolic pressure (LVEDP; 12.0 mmHg) compared to baseline (15.5 mmHg; P < 0.01) and to metoprolol succinate (17.1 mmHg; P < 0.01), and a reduced NT-proBNP level (525.4 pg/ml) compared to baseline (3826.3 pg/ml; P < 0.01) and to metoprolol succinate (1038.9 pg/ml; P < 0.01). Five-year post-transplant survival was significantly better in patients with ivabradine (90.0%) versus metoprolol succinate (68.5%; P < 0.01). Conclusion: Patients receiving ivabradine showed a superior heart rate reduction and a better left ventricular diastolic function along with an improved 5-year survival after HTX. [ABSTRACT FROM AUTHOR]

A quick and simple reversed-phase High-Performance Liquid Chromatographic method (RP-HPLC) with isocratic elution has been developed and validated for the concurrent quantitative determination of chlorthalidone, metoprolol succinate and telmisartan in the bulk mixture and tablet dosage form. The chromatographic separation was performed using Inertsil Octadecyl-Silica (ODS- C18) Column (150mmx4.6mm, 5μm) stationary phase. The separation and elution was carried out using a mobile phase mixture of phosphate buffer (50 mM, pH 2.5) and acetonitrile at a ratio of 40:60 v/v and 0.7 mL/min flow rate. Chlorthalidone, metoprolol succinate and telmisartan were eluted at 2.96±0.5 min, 4.31±0.5 min and 5.94±0.5 min respectively. The response was recorded using a photodiode array (PDA) detector at 225 nm wavelength. The selected method was linear in the range of 3.21-18.72 µg/mL, 6.25-37.50 µg/mL and 10-60 µg/mL while percentage recovery was in the range from 99.15 to 99.93%, 99.15 to 99.42% and 100.03 to 100.08% for chlorthalidone, metoprolol succinate and telmisartan respectively. The method was found to be sensitive, selective, linear and reproducible and the results obtained suggest the suitability of the developed method for routine analysis of the formulations containing the combination of these drugs. [ABSTRACT FROM AUTHOR]

A high-performance liquid chromatographic and UV spectrophotometric method were developed and validated for the quantitative determination of three anti-hypertensive drugs viz. Metoprolol succinate, Telmisartan and Cilnidipine in pure bulk and tablet dosage form. The different validation parameters such as linearity, precision, accuracy and specificity, limit of detection (LOD) and limit of Quantification (LOQ) were determined according to the International Conference on Harmonization ICH Q2 guidelines. The UV spectrophotometric determinations were performed at 224 nm, 299 nm, and 242 nm for Metoprolol succinate, Telmisartan, Cilnidipine respectively. Chromatography was carried out by isocratic technique on a reversed-phase Luna C18 phenomenix column (250 mm × 4.6 mm × 5 µm) thermo stated HPLC column with Acetonitrile and water (90:10) as mobile phase based and optimized depending on the polarity of the molecules. The linearity of the calibration curves for each analyte in the desired concentration range is good (r2>0.999) by both the HPLC and UV methods. Moreover, the accuracy and precision obtained with HPLC correlated well with the UV method which implied that UV spectroscopy can be a cheap, reliable and less time consuming alternative for chromatographic analysis. The proposed methods are highly sensitive, precise and accurate and hence were successfully applied for the reliable quantification of API content in the commercial formulations of Metoprolol succinate, Telmisartan and Cilnidipine. [ABSTRACT FROM AUTHOR]

RP-HPLC method has been developed along with stability indicating attribute for simultaneous estimation of Metoprolol Succinate and Chlorthalidone in bulk and in tablet dosage form with minimized drug extraction steps. The chromatographic analysis was performed isocratically by using Oyster ODS3, 150-4.6 mm column having particle size of 5 µm (Merck & Co.) as stationary phase maintained at ambient temperature (about 25°C) with 1.0 mL/min of flow rate and 20 mM phosphate buffer having pH 2.3 (adjusted with10% orthophosphoric acid) and Acetonitrile (650:350, v/v) as Eluent at wavelength 225 nm. Individual drug substances as well as combination drug product was subjected to acid, alkali, oxidative, photolytic, thermal and humidity degradation, the peaks due to degraded product were significantly separated out from active analytes peak. The method was validated for the specificity, linearity, detection limit, quantitation limit, precision, accuracy, robustness and solution stability as per ICH guidelines and successfully used for regular analysis. [ABSTRACT FROM AUTHOR]

Background: Natural gums and mucilage's are an alternative to synthetic drug release modifiers. These natural plant materials are cost effective, biocompatible, and biodegradable, and they have fewer side effects. The key purpose of this study was to formulate and characterize sustained-release tablets of Metoprolol succinate using Eulophia herbacea tuber mucilage as a novel polymer. Sustained release matrix tablets were prepared by wet granulation. The tablets were characterized for thickness, diameter, hardness, drug content, weight variation, friability, swelling index and in-vitro drug release. Results: The tablets passed all the tests required. The dissolution profile of the tablets revealed that the release of the drug was sustained up to 22 hours compared with a reference tablet formulation, PROLOMET XI 100. The dissolution profile data were fitted to release kinetic models such as zero order kinetics, first order kinetics, the Higuchi model, and the Korsmeyer-Peppas model to study the pattern of release of the drug from each formulation. The prepared sustained release tablet formulation was compared with a marketed formulation (reference formulation) in a dissolution study. The factors f1 (difference factor) and f2 (similarity factor) were determined. Conclusions: As the concentration of the Eulophia herbacea mucilage decreased, the rate of drug release from the formulation decreased. The best formulation was one that contained 20% Eulophia herbacea mucilage. Its drug release profile was comparable with the reference formulation with an f1 value of 10.9% and an f2 value of 62.9%. The study of the release kinetics indicated that the tablet formulation exhibits an anomalous (non-Fickian) diffusion pattern and the release of drug is governed by diffusion-controlled as well as swellingcontrolled mechanisms. [ABSTRACT FROM AUTHOR]

The development of extended-release dosage forms with adequate drug release is a challenge for pharmaceutical companies, mainly when the drug presents high solubility, as in Biopharmaceutics Classification System (BCS) class I. This study aimed to develop extended-release mini-tablets containing metoprolol succinate (MS), while integrating design of experiments (DOE) and physiologically based biopharmaceutics modeling (PBBM), to predict its absorption and to run virtual bioequivalence (VBE) studies in both fasted and fed states. Core mini-tablet formulations (F1, F2, and F3) were prepared by direct compression and coated using nine coating formulations planned using DOE, while varying the percentages of the controlled-release and the pore-forming polymers. The coated mini-tablets were submitted to a dissolution test; additional formulations were prepared that were optimized by simulating the dissolution profiles, and the best one was submitted to VBE studies using GastroPlus® software. An optimized formulation (FO) containing a mixture of immediate and extended-release mini-tablets showed to be bioequivalent to the reference drug product containing MS when running VBE studies in both fasted and fed states. The integration of DOE and PBBM showed to be an interesting approach in the development of extended-release mini-tablet formulation containing MS, and can be used to rationalize the development of dosage forms.

• New methods were developed for simultaneous determination of olmesartan medoxomil and metoprolol succinate. • Area under the curve and ratio difference spectrophotometric methods were used. • The developed methods are simple, accurate and co-friendly with excellent greenness on Eco-scale. • The developed methods are economic and time saving. The aim of this study is to develop and validate two simple spectrophotometric methods for simultaneous determination of metoprolol succinate (MET) and olmesartan medoxomil (OLM) in tablet form. Method (I) was area under the curve (AUC) method. This approach involved the measuring of the area over a variety of wavelengths. Two wavelength ranges; 213–230 nm and 244–266 nm were chosen for determination of MET and OLM, respectively. Method (II) was ratio difference spectrophotometric method. For determination of MET, the ratio spectra were generated using 15 μg/mL OLM as a divisor then the peak to trough amplitudes between 221 nm and 245 nm were displayed versus the corresponding concentrations of MET. For determination of OLM, the peak-to-peak amplitudes between 247 and 293 nm were chosen and found to be directly proportional to OLM concentrations using 15 μg/mL MET as a divisor. The linearity ranges were 2–30 μg/mL and 2–25 μg/mL for MET and OLM, respectively. The assay results showed good mean %recovery ± SD as well as good agreement with that of the reported method. The developed methods were validated according to ICH guidelines. The developed methods are accurate, precise, eco-friendly and could be applied successfully to estimate OLM and MET in their combined dosage form. [ABSTRACT FROM AUTHOR]

The development of new drugs that combine active ingredients for the treatment hypertension is critically essential owing to its offering advantages for both patients and manufacturers. In this study, for the first time, detailed development of a scalable process of film-coated bi-layer tablets containing sustained-release metoprolol succinate and immediate-release amlodipine besylate in a batch size of 10,000 tablets is reported. The processing parameters of the manufacturing process during dry mixing-, drying-, dry mixing- completion stages were systematically investigated, and the evaluation of the film-coated bi-layer tablet properties was well established. The optimal preparation conditions for metoprolol succinate layer were 6 min- dry mixing with a high-speed mixer (120 rpm and 1400 rpm), 30-min drying with a fluid bed dryer, and 5-min- mixing completion at 25 rpm. For the preparation of amlodipine besylate layer, the optimal dry-mixing time using a cube mixer (25 rpm) was found to be 5 min. The average weight of metoprolol succinate layers and bi-layer tablets were controlled at 240–260 mg and 384–416 mg, respectively. Shewhart R chart and X¯ charts of all three sampling lots were satisfactory, confirming that the present scalable process was stable and successful. This study confirms that the manufacturing process is reproducible, robust; and it yields a consistent product that meets specifications.

Present work focusing in developing and validating a new high performance liquid chromatography method for estimation of Meto prolol Succinate and Benidipine Hydrochloride in their combine tablet dosage form. The method was performed on Shimadzu LC-20AT instrument using C18 (250 mm x 4.6 mm, 5 µm) Hypersil BDS Column and Potassium Dihydrogen Phosphate Buffer (pH 4.0): Methanol (65: 35% v/v) as mobile phase at ambient temperature. Detection was carried out at 269 nm. Concentration range 4-12 µg/ml for Benidipine Hydrochloride and 25-75 µg/ml for Metoprolol Succinate . The Percentage recovery of Benidipine Hydrochloride and Metoprrolol succinate was found to be 99.59% and 99.39 respectively. Correlation coefficient for Metoprolol succinate and Benidipine Hydrochloride was found 0.9995 and 0.9997 respectively. The Rt values for Metoprolol succinate and Benidipine Hydrochloride were found to be 3.4 and 5.9 min respectively. The method was validated according to the guidelines of International Conference on Harmonisation (ICH) and was successfully employed in the estimation of commercial formulations. [ABSTRACT FROM AUTHOR]

This review focus upon compatibility study of Sucralfate and Metoprolol Succinate being administrated as Bilayer floating tablet and its implementation in treatment of ulceration and hypertension in pregnancy.This review is prepared by focusing upon, characteristics study of Sucralfate and Metoprolol succinate, Drug interaction between the two drugs and study about fulfilment of criteria of Bilayered floating tablet. The ulcer protective Sucralfare is simpler and more effective H2 blockers and antihypertensive Metoprolol succinate the ß1 receptor blocker fulfilling all the criteria of Bilayer floating tablet. They can be implemented in case of pregnancy and lactation as a combined form in empty stomach. As bi layered floating tablet Sucralfate can act as immediate release layer and Metoprolol Succinate can act as sustained release layer and improve the controlled delivery of drug for prolonged period of time at desired rate and improve the bioavailability and which ideal doses form attains the desired therapeutic concentration of drug in plasma and maintains constant frequency for entire duration of treatment. [ABSTRACT FROM AUTHOR]

The review based upon characteristics ofMetoprolol Succinate and its implementation in treatment of hypertension in pregnancy as a form of Bilayer floating tablet.This review is prepared by focusing onhypertension during pregnancy, characteristics study of Metoprolol succinate and fulfilment of acceptance criterias ofBilayered floating tablet. Antihypertensive Metoprolol succinate is the ß1 receptor blocker. It can be implemented in case of pregnancy and lactation as a combined formwith other drugs in empty stomach. As bi layered floating tablet Metoprolol Succinate can act as sustained release layer and improve the controlled delivery of drug for prolonged period of time at stomach region by maintaining proper floating lag time and total floating time as bouncy study and improve the bioavailability and maintains consistency at entire sustained period. [ABSTRACT FROM AUTHOR]

A rapid and easy liquid chromatography-tandem mass spectrometry (LC--MS/MS) method was developed, validated, and used to quantify amlodipine besylate and metoprolol succinate in human plasma. Hydrochlorothiazide was used as the internal standard. LC--MS/MS with electrospray ionization in the positive ionization mode was performed under multiple reaction monitoring to examine analytes, which were drawn from human plasma via liquid--liquid extraction using a mixture of diethyl ether and dichloromethane (6:4). The extracts were dried under a nitrogen stream at 40°C, after which the samples were dissolved in a mixture of methanol and water (80:20). The re-dissolved samples were injected onto a C18 column and eluted using a mixture of methanol and 0.4% formic acid (80:20) as the mobile phase. Linear standard calibration was performed, and lower limits of quantification were determined for each analyte. The developed method was fully validated with respect to selectivity and carryover, as well as intra- and inter-day accuracy and precision in accordance with guidelines of the United State Food and Drug Administration and the European Medicines Agency. Mean analyte recovery was between 71.72% and 97.55%, and matrix effects exerted only a minor influence on precision. The validated method was applied in a clinical bioequivalence study to evaluate the in vivo bioequivalence of two commercial products containing 5 mg amlodipine and 50 mg metoprolol. This randomized, single-dose, two-treatment, three-period, two-sequence, open-label, crossover study involved 14 healthy subjects, and a twoweek washout period between the two phases of the research was implemented. Standard pharmacokinetic parameters were calculated to compare a test product with Selomax® as the reference. [ABSTRACT FROM AUTHOR]

Metoprolol succinate is a β1 selective antagonist used as an Anti-hypertensive, Anti arrhythmic, Anti Angina. The aim of present investigation was to develop matrix tablets of Metoprolol succinate using different polymers. Metoprolol succinate matrix tablet was prepared by use of xanthan gum and carbopol-934 as a polymer initially by direct compression methods. Physicochemical compatibility of the drug with polymer was confirmed by IR spectroscopy and DSC. Metoprolol succinate matrix tablets were prepared by direct compression and wet granulation method using different polymers. All the formulations were evaluated for weight variation, thickness, hardness, friability and dissolution. The result of matrix tablets formulation (A-4) showed drug release 94.12% in 720 min. Therefore it was concluded that formulation (A-4) containing carbopol-934 and xanthan gum in the ratio of 80:20 showing promising result for sustained release of Metoprolol succinate, further for improvement of release profile in situ interpolymeric complexes of both carbopol and xanthan gum were tried. All the formulations were evaluated for weight variation, thickness, hardness, friability and dissolution. The results of IPC formulation B-11 showed drug release 96.29% in 720 min. It was concluded that tablets were prepared by using in-situ inter polymer complex formed with 70:30 ratio of Carbopol and Xanthan gum solution as binder. Formulation B-11 showed promising result because of its resistance in pH 1.2 HCL buffer for more than 2 hrs showed the maximum sustained release as compared to simple matrix tablet because of more acid resistance of the complex. Thus, sustained release matrix tablets of Metoprolol succinate using biocompatible polymers were successfully formulated, evaluated and found to be suitable candidates in extending the release of the drug from the matrix tablets. [ABSTRACT FROM AUTHOR]

A model process, previously developed in a series of studies, allows for the transfer of thin-layer chromatography (TLC) methods for qualitative screening of counterfeit drug products published in the Global Pharma Health Fund (GPHF) Minilab manual and US Food and Drug Administration (FDA) Compendium of Unofficial Methods for Screening of Pharmaceuticals by TLC to quantitative high-performance TLC (HPTLC)-densitometry methods. This article describes HPTLC-densitometry methods developed and validated according to this model process for pharmaceutical products of amiodarone HCl, carvedilol, doxylamine succinate, magnesium salicylate, metoprolol succinate, nebivolol HCl, and salicylamide, for which qualitative screening methods have not been published in the Minilab manual or FDA Compendium. These methods use relatively inexpensive and nontoxic "green solvents" for sample and standard solution and mobile phase preparation, Merck Premium Purity silica gel 60 F254 plates, automated standard and sample solution bandwise application, and automated densitometry for the assessment of peak purity and identity and quantification. Corresponding to the quantitative HPTLC-densitometry methods, qualitative TLC screening methods for these drug products were developed and posted online with open access as supplements to the FDA Compendium. [ABSTRACT FROM AUTHOR]

The current study reports on the manufacturing of extended release dosage forms of metoprolol succinate via hot-melt extrusion (HME) technology. Either Eudragit®S100 and Eudragit®L100 alone or in combination with release modifying agent Polyox™ WSR 303 and Eudragit®L100-55 were processed to obtain complete and faster release. Metoprolol succinate with similar solubility parameters to polymer was dispersed in polymer matrix and was characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Stability of drug after extrusion was confirmed by thermogravimetric analysis and high-performance liquid chromatography. Physical characterization method exhibited that the drug was homogeneously dispersed in non-crystalline state in Eudragit®L100-55-based formulations whereas in semi-crystalline state in Polyox™ WSR 303. The drug release percentage was below 3 and 40% in 0.1 N HCL with Eudragit®L100-55- and Polyox™ WSR 303-containing formulations, respectively, and exhibited pH-dependent dissolution properties. The drug-release mechanism was anomalous with Polyox™ WSR 303 formulations whereas diffusion through pore formation was obtained with Eudragit®L100-55. Both Eudragit®L100-55 and Polyox™ WSR 303 changed the release mechanism and kinetics of drug release from thermally processed dosage forms. The optimized stable formulation is similar to the marketed formulation with F2 value of 72.36. Thus, it can be concluded that HME was exploited as an effective process for the preparation of controlled release matrix system based on pH-dependent polymer matrices Eudragit®S100 and Eudragit®L100. [ABSTRACT FROM AUTHOR]

The article focuses on the use of b-blockers for the treatment of arterial hypertension (AH). Given the situation of modern Russian and European recommendations about the place of b-blockers in the treatment of AH, including their benefits with a combination of hypertension with coronary heart disease, chronic heart failure, atrial fibrillation. Analyzed the efficacy and safety of b-blockers in diabetes mellitus, metabolic syndrome, dyslipidemia, peripheral artery, chronic obstructive pulmonary disease, sexual dysfunction, in individuals of different age and gender. It is emphasized that the selection of b-blockers inside of a class is determined by its selectivity, the study in clinical studies, pharmacokinetic characteristics. Data about efficiency and safety of application of metoprolol succinate.

The article focuses on the use of b-blockers for the treatment of arterial hypertension (AH). Given the situation of modern Russian and European recommendations about the place of b-blockers in the treatment of AH, including their benefits with a combination of hypertension with coronary heart disease, chronic heart failure, atrial fibrillation. Analyzed the efficacy and safety of b-blockers in diabetes mellitus, metabolic syndrome, dyslipidemia, peripheral artery, chronic obstructive pulmonary disease, sexual dysfunction, in individuals of different age and gender. It is emphasized that the selection of b-blockers inside of a class is determined by its selectivity, the study in clinical studies, pharmacokinetic characteristics. Data about efficiency and safety of application of metoprolol succinate.

Relationship of metoprolol clinical efficacy with its different salts (tartrate, succinate, fumarate) as well as its presentations (tablets with immediate, controlled or sustained release) is analyzed. It is highlighted that pharmacodynamic properties depend on metoprolol molecule only. These properties do not change after modification of drug presentation or metoprolol plasma concentration which depends on velocity of drug release from the tablet. Data of randomized clinical trials are discussed in regard to development of evidence base for use of different metoprolol presentations in treatment of patients with arterial hypertension, unstable angina, myocardial infarction, heart failure. Indications for tartrate and succinate salts of metoprolol are presented. Results of clinical studies on efficacy of metoprolol tartrate in long-acting drug presentations are analyzed.

Aim. To estimate metoprolol succinate effect on regulatory and adaptive status (RAS) of patients with сhronic heart failure (CHF) functional class (FC) I and arterial hypertension (HT) I-II stages. Material and methods. 51 patients with CHF FC I and HT I-II stage, (30 men and 21 women aged 52.6±1.4 yeas). Cardio-respiratory synchronism (CRS) test, 6-minute walking test, tread-mill burden test with registration of maximal oxygen consumption, 24-hour blood pressure monitoring, echocardiography and determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) blood level were performed initially and after 6 months of therapy with metoprolol succinate (dose 78.1±5.7 mg/day) in sustained-release presentation. Results. Metoprolol succinate therapy had no significant effect on RAS (there was no unidirectional dynamics of the basic CRS test parameters: a range of synchronization decreased significantly from 8.8±0.4 to 7.2±0.6 сardio-respiratory cycles per minute (in 18%; р