Metoprolol Tartrate Tablets Research Articles

Off-the-shelf medication transformed: Custom-dosed metoprolol tartrate tablets via semisolid extrusion additive manufacturing and the perception of this technique in a hospital context

Pharmacies are currently unable to stock proper oral dosage forms for pediatric populations. This leads to manipulation of medications or the need to compound specialized medications, which can be a time-consuming process. Using Semisolid Extrusion (SSE) additive manufacturing (AM), specialized medications can be produced in an expedited process from off-the shelf medication in a hospital or outpatient pharmacy setting. In this study, tablets with a desired dose of 5 mg of metoprolol tartrate derived from commercial Seloken™ 50 mg tablets were 3D printed in a hospital setting. Validation testing was done on five batches, highlighting tablets with a high uniformity in mass and dimension, drug content, acceptable microbial assays, and prolonged release during in-vitro analysis. The average drug content found for the tablets was within ±6% of 5 mg for all batches produced. Comparisons were done between the SSE tablets and capsules produced in an external compounding facility, highlighting several positive aspects of SSE-produced tablets beyond simply shortening the production timeline. The SSE tablets printed in this study are characterized by their smaller size, enhanced prolonged release properties, and more uniform drug content across the tested samples. Additionally, interviews with pharmaceutical professionals were conducted to determine the positive aspects of SSE and further improvements to bring this technique as seamlessly as possible into the pharmacy. This study underscores the feasibility of employing SSE in the production of specialized medications within a hospital environment. Furthermore, it highlights the methodological advantages SSE offers over existing production standards, demonstrating its potential to improve pharmaceutical manufacturing in healthcare settings.

Napex acupoint thread-embedding combined with metoprolol tartrate tablet for prophylactic treatment of migraine without aura: a randomized controlled trial.

To observe the efficacy of napex acupoint thread-embedding combined with metoprolol tartrate tablet for prophylactic treatment of migraine without aura, and to compare its efficacy with simple napex acupoint thread-embedding and simple metoprolol tartrate tablet. A total of 105 patients with migraine without aura were randomized into a combination group (35 cases, 5 cases dropped out), a thread-embedding group (35 cases, 4 cases dropped out) and a western medication group (35 cases, 2 cases dropped out). In the thread-embedding group, napex acupoint thread-embedding was applied at bilateral Fengchi (GB 20) and points of 1.5 cun nearby to the lower edge of spinous process of cervical 2. In the western medication group, metoprolol tartrate tablet was given orally, 12.5 mg a time, twice a day. In the combination group, napex acupoint thread-embedding combined with oral metoprolol tartrate tablet was delivered. The treatment of 8 weeks was required in the 3 groups. The days of headache attacks, frequency of headache attacks, headache severity (visual analogue scale [VAS] score) and the migraine specific quality of life questionnaire version 2.1 (MSQ) score were observed during baseline period (4 weeks before treatment to before treatment), observation period (1-4 weeks and 5-8 weeks in treatment) and follow-up period (1-4 weeks after treatment completion) respectively, the proportions of the days of headache attacks/frequency of headache attacks relieved by 50% were calculated, and the safety was evaluated in the 3 groups. During the observation period and the follow-up period, the days of headache attacks, frequency of headache attacks and headache VAS scores in the 3 groups were reduced compared with those of the baseline period (P<0.05). During the observation period and the follow-up period, the days of headache attacks and the frequency of headache attacks in the combination group were lower than those in the thread-embedding group and the western medication group (P<0.05); during the observation period (1-4 weeks in treatment), the headache VAS scores in the combination group and the thread-embedding group were lower than that in the western medication group (P<0.05); during the observation period (5-8 weeks in treatment) and the follow-up period, the headache VAS scores in the combination group were lower than those in the thread-embedding group and the western medication group (P<0.05). During the observation period and the follow-up period, the scores of role restriction, role prevention and emotion function of MSQ in the combination group were increased compared with those of the baseline period (P<0.05); during the observation period (5-8 weeks in treatment) and the follow-up period, the role prevention scores of MSQ in the thread-embedding group and the western medication group were increased compared with those of the baseline period (P<0.05); during the follow-up period, the emotion function scores of MSQ in the thread-embedding group and the western medication group were increased compared with those of the baseline period (P<0.05). During the observation period and the follow-up period, the scores of role restriction, role prevention and emotion function of MSQ in the combination group were higher than those in the thread-embedding group and the western medication group (P<0.05). There was no statistical difference in the proportions of the days of headache attacks/frequency of headache attacks relieved by 50% among the 3 groups (P>0.05), and there were no serious adverse reactions in the 3 groups. Napex acupoint thread-embedding combined with metoprolol tartrate tablet, simple napex acupoint thread-embedding and simple metoprolol tartrate tablet all can reduce the days of headache attacks and the frequency of headache attacks, relieve headache severity and improve the quality of life in patients with migraine without aura. Napex acupoint thread-embedding combined with metoprolol tartrate tablet has a better effect.

Lyophilized recombinant human brain natriuretic peptide: A promising therapy in patients with chronic heart failure.

Lyophilized recombinant brain natriuretic peptide (BNP) is an exogenous peptide synthesized by artificial recombination technology, with a similar structure and similar physiological effects with the endogenous natriuretic peptide secreted by the human body. It's main mechanism of action is to increase cyclic guanosine monophosphate by binding with its corresponding receptor in the body, regulating, thus, the imbalance of the vascular system and cardiac hemodynamics, improving the heart's pumping capacity, and inhibiting sympathetic excitability and myocardial remodeling. Moreover, it can promote mitochondrial metabolism and enhance the use of adenosine triphosphate in cardiomyocytes. In the present study, 102 chronic heart failure (HF) patients were randomly assigned to a control and an observation group consisting of 51 patients each. Patients of the control group were treated with standard HF therapy for 3 d including oral metoprolol tartrate tablets, spironolactone, and olmesartanate while patients of the observation group were administered the recombinant human BNP injection for the same time-period, plus the standard HF therapy. The recombinant human BNP group (observation group) demonstrated better physical, emotional, social, and economic scores, as well as cardiac and inflammatory biomarkers such as serum hypersensitive C-reactive protein, N-terminal pro BNP and troponin I levels, compared to the control group. Moreover, cardiac function was also improved, as left ventricular ejection fraction and stroke volume were significantly higher in the observation group than in the control group. Interestingly, adverse reactions were not different between the 2 groups. However, these results are not generalizable and the need of large multicenter randomized controlled trials examining the safety and efficacy of recombinant human BNP in HF patients is of major importance.

Quantitative analysis of 3-isopropylamino-1,2-propanediol as a degradation product of metoprolol in pharmaceutical dosage forms by HILIC-CAD

Aryloxypropanolamine is an essential structural scaffold for a variety of β-adrenergic receptor antagonists such as metoprolol. Molecules with such a structural motif tend to degrade into α, β–hydroxypropanolamine impurities via a radical–initiated oxidation pathway. These impurities are typically polar and nonchromophoric, and are thus often overlooked using traditional reversed phase chromatography and UV detection. In this work, stress testing of metoprolol confirmed the generation of 3-isopropylamino-1,2-propanediol as a degradation product, which is a specified impurity of metoprolol in the European Pharmacopoeia (impurity N). To ensure the safety and quality of metoprolol drug products, hydrophilic interaction chromatography (HILIC) methods using Halo Penta HILIC column (150 mm × 4.6 mm, 5 μm) coupled with charged aerosol detection (CAD) were developed and optimized for the separation and quantitation of metoprolol impurity N in metoprolol drug products including metoprolol tartrate injection, metoprolol tartrate tablets, and metoprolol succinate extended-release tablets. These HILIC-CAD methods were validated per USP validation guidelines with respect to specificity, linearity, accuracy, and precision, and have been successfully applied to determine impurity N in metoprolol drug products.

In Vitro Assessment of Nasal Insufflation of Comminuted Drug Products Designed as Abuse Deterrent Using the Vertical Diffusion Cell.

In vitro evaluation of abuse deterrent formulations (ADFs) is a challenge since real abuse situations are variable and ADF technology is evolving. Specifically, an assessment of an ADF to deter nasal insufflation would be valuable. In this study, a vertical diffusion cell (VDC) was used to evaluate polyethylene oxide (PEO)-based tablets manipulated by three different forces. The commercially available products Oxycontin®, an ADF, Opana®, and metoprolol tartrate tablet formulations made in our laboratory were studied. Particle size distribution and percent recovery of manipulated tablets were measured. Grinding produced the lowest recovery and the smallest particle size distribution. Drug release was examined using a VDC by placing the dry comminuted particles on an enclosed wetted cellulose membrane. Dispensing dry particles on a VDC is atypical but includes some key features associated with an abuse situation where once the particles are snorted, the moisture in the nasal mucosa activates hydration and swelling of the polymers in the formulation, retarding drug release. Drug release from OxyContin®, Opana®, and metoprolol tablets were analyzed for the cutting, grinding, and milling modes of abuse. The analysis showed that in most cases, the mode of abuse produced different particle sizes with different release rates. Statistically different release rates were observed for metoprolol tablets made with different molecular weight PEO and with different porosities. These results indicate that within detection limits, the VDC can be used to quantitate release differences due to various modes of abuse used in this study.

Formulation of Metoprolol Bilayer Tablets as an Oral Modified Release Dosage Form

Metoprolol is a β1 adrenergic blocker used in treatment of heart diseases. Metoprolol (100mg) tablets was formulated as a modified release oral system utilizing the concept of bilayer system, first layer contained (30mg) as immediate release and the other (70mg) in the sustained release matrix. The immediate release layer consisted of lactose or microcrystalline cellulose as diluents with sodium starch glycolate or sodium croscarmellose as disintegrants. The result showed that the layer contains microcrystalline cellulose and 2% sodium starch glycolate gave disintegration time similar to that of conventional metoprolol tartrate tablet. This result was subjected in the subsequent preparation of the bilayer tablet. The sustained release layer was prepared using three polymers: ethylcellulose (EC), Hydroxypropyl methylcellulose (HPMC) and hydroxyl ethylcellulose (HEC) as retardant materials. It was found that the combination of EC with HPMC in ratio of 2:1 in F11 was best formula because of it’s release profile and the tablet integrity and dimensions were conserved for the period of the test, but according to similarity factor (f ­2­), F15 (which contained EC:HPMC in ratio 2:1 with polyvinyl pyrrolidone (PVP) as a binder) was the best formula showed higher (f2­) among all other formulas and equals to 72.3 comparing to reference product.&#x0D; Key words: Metoprolol, Bilayer tablet, Immediate release, Sustained release.

Swallowing‐induced atrial tachycardia: case report

A 53-year-old man presented with heart palpitations while swallowing. Electrophysiologic study (EPS) and immunohistochemical results of his esophageal leiomyoma suggested that swallowing-induced atrial tachycardia is related with neural reflex. S100-immunopositive nerve fibers are demonstrated sympathetic nerves which possibly explain the mechanism. Metoprolol tartrate tablets are effective in our patient.

Development and validation of reverse phase high performance liquid chromatographic method for the estimation of metoprolol tartrate tablets 50, 100 mg

Development and validation of reverse phase high performance liquid chromatographic method for the estimation of metoprolol tartrate tablets 50, 100 mg

Identification, synthesis, isolation and characterization of new impurity in metoprolol tartrate tablets

A new unknown impurity was observed in accelerated stability studies of Metoprolol tartrate tablets. This impurity has been identified, synthesized and characterized through different spectral studies and confirmed as an adduct of lactose and Metoprolol formed by Maillard reaction.

ASSA14-07-02 Comparision of metoprolol succinate sustained-release tablets and metoprolol tartrate tablets on cardiac function in patients with chronic congestive heart failure

Background To investigate the effect of Metoprolol succinate sustained-release tablets and Metoprolol tartrate tablets on cardiac in chronic congestive heart failure patients. Methods 182 patients with clinical data, who suffered with chronic congestive heart failure were collected, and 67 cases were excluded. The patients were divided into 2 groups according to the different types of dosage forms: Metoprolol succinate sustained-release tablets group and Metoprolol Tartrate Tablets group. Patients in Metoprolol Tartrate Tablets group took 25 mg-50 mg Metoprolol Tartrate Tablets every day, while patients in the other group took 23.75–95 mg metoprolol succinate sustained-release tablets every day. Average heart rate, LVDd, EF, BUN and Crea were measured. Results Compared with Metoprolol Tartrate Tablets, Metoprolol succinate sustained-release tablets decreased average heart rate in chronic congestive heart failure patients (64.0 ± 5.4 vs 69.5 ± 7.6, p Conclusions Metoprolol succinate sustained-release tablets decreased average heart rate in chronic congestive heart failure patients compared with Metoprolol Tartrate Tablets. The effect on cardiac and renal function was equal.

Comparative stability of repackaged metoprolol tartrate tablets

The stability of metoprolol tartrate tablets packaged in original high density polyethylene containers and repackaged in USP Class A unit-dose blister packs was investigated. Studies were conducted at 25 °C/60% relative humidity (RH) for 52 weeks and at 40 °C/75% RH for 13 weeks. The potency, dissolution, water content, loss on drying and hardness of the drug products were analyzed. Results indicated no differences in the stability between the tablets in both packages stored under 25 °C/60% RH. No difference in potency was found in both packages under either condition. However, a significant weight increase due to moisture uptake was observed for the repackaged tablets stored under 40 °C/75% RH. The weight increase was accompanied by a decrease in tablet hardness (6.5–0 kp) and a increase in dissolution rate (51–92%) in 5 min. Near-infrared (NIR) chemical imaging also monitored moisture uptake of the tablet non-invasively through the package. The observed changes in product stability may adversely affect the products bioavailability profile, even though the potency of the active drug remained within USP specification range of 90–110%. Study results suggest product quality can be negatively impacted even when using USP Class A repackaging materials.

Process Analytical Technology: Chemometric Analysis of Raman and Near Infra-Red Spectroscopic Data for Predicting Physical Properties of Extended Release Matrix Tablets

The purpose of this work was to develop a correlation between pharmaceutical properties such as hardness, porosity, and content with prediction models employed using Raman and near infra-red (NIR) spectroscopic methods. Metoprolol tartrate tablets were prepared by direct compression and wet granulation methods. NIR spectroscopy and chemical imaging, and Raman spectra were collected, and hardness, porosity, and dissolution were measured. The NIR PLS model showed a validated correlation coefficient of >0.90 for the predicted versus measured porosity, hardness, and amount of drug with raw and second derivative NIR spectra. Raman spectra correlated porosity of the tablets using raw data for directly compressed tablets and wet granulated tablets (r(2) > 0.90). A very close root-mean square error of calibration (RMSEC) and root-mean square error of prediction (RMSEP) values were found in all the cases indicating validity of the calibration models. Raman spectroscopy was used for the first time to predict physical quality attribute such as porosity successfully. Chemical imaging utilizing NIR detector also demonstrated to show physical changes due to compression differences. In conclusion, sensor technologies can be potentially used to predict physical parameters of the matrix tablets.

Does coronary artery bypass surgery affect metoprolol bioavailability

beta-blockers are commonly administered in patients with coronary artery bypass surgery (CABG). Despite this therapy, however, the incidence of postoperative atrial fibrillation (AF) is high (9-19%), and it is unknown why the beta-blockers do not reduce the incidence of AF more efficiently. In this pharmacokinetics study, in which the patients acted as their own controls, we have evaluated the bioavailability of perioperative metoprolol tablets in CABG surgery patients. Twelve male patients, aged 45-64 years, scheduled for CABG surgery were administered an initial 50 mg metoprolol tartrate tablet orally on the morning of the preoperative day and thereafter at 12-h intervals. Regular blood samples were collected up to 12 h after the first administration of the drug on the preoperative day as well on the first and third postoperative days. The plasma concentration for metoprolol was analyzed (limit of quantification = 0.001 mg/L) using liquid chromatography-tandem mass spectrometry. The bioavailability of the metoprolol was significantly less on the first postoperative day, with AUC(0-12) values ranging from 0.7 to 17.1 (median: 7.2) mg min/L, than on the preoperative day, with AUC(0-12) values of 5.1-26.7 (12.6) mg min/L; however, it returned to the preoperative values on the third postoperative day, with AUC(0-12) values of 3.5-25.2 (15.2) mg min/L. Similar changes were observed in C(max) values: preoperative C(max) ranged between 0.026 and 0.123 (0.060) mg/L, on the first postoperative day, the C(max) ranged between 0.003 and 0.093 (0.025) mg/L, and on the third postoperative day, the C(max) ranged between 0.009 and 0.136 (0.061) mg/L. There was no correlation between the pharmacokinetic parameters and patient characteristics, but both the preoperative C(max) and C(60) correlated significantly with the postoperative C(max) (Pearson correlation coefficient: 0.61-0.72). One patient with one of the lowest rates and extent of metoprolol absorption developed AF. This study indicates that the bioavailability of metoprolol is markedly reduced when administered in tablet form during the early phase after CABG.

Novel Metrics to Compare Dissolution Profiles

Purpose: To evaluate four novel metrics that compare dissolution profiles and assess their performance characteristics by comparing dissolution profiles of FAST and SLOW immediate release metoprolol tartrate tablets.Methods:The four novel metrics (ρ, ρm, δa, and δs), along with f2, were applied to dissolution data from FAST and SLOW metoprolol tartrate tablets. For example, ρm is defined as:where Rt is the percent dissolved of the reference product at time t, Tt the percent dissolved of the test product at time t, and RATIOt the larger of either Rt/Tt or Tt/Rt. The mean metric values, upper (or lower) confidence limits, and skewness values were calculated, in order to characterize the performance of each metric.Results: The mean values of ρ, ρm, δa, δs, and f2 were 1.80, 0.80, 0.47, 0.36, and 19.6, respectively. The novel metrics indicate that greater than a 50% relative difference exists between the FAST and SLOW profiles. The upper 95% confidence limits for ρ, ρm, δa, and δs were 1.84, 0.83, 0.48, and 0.38, respectively, with f2 having a lower limit of 19.1. Skewness values for ln-transformed ρ, ρm, δa, δs, and f2 were 0.81, 0.71, 0.86, 0.47, and −0.94, respectively, suggesting favorable metric distribution properties.Conclusions: The direct curve comparison metrics ρ, ρm, δa, and δs appear to be viable methods to compare dissolution profiles, particularly ρm.

Scale-up effects on dissolution and bioavailability of propranolol hydrochloride and metoprolol tartrate tablet formulations

Scale-up effects on dissolution and bioavailability of propranolol hydrochloride and metoprolol tartrate tablet formulations

Dependence of In Vitro-In Vivo Correlation Analysis Acceptability on Model Selections

ABSTRACTThe objectives of this study were to assess the influence of pharmacokinetic and dissolution model selection on the success of in vitro–in vivo correlation (IVIVC) analysis of fast-, medium-, and slow-dissolving metoprolol tartrate immediate-release tablet formulations. Several different compartmental models were fit to the fast formulation plasma data. Three candidate models with the best fits were ranked 1, 2, and 3 and used to predict AUC and Cmax of the medium and slow formulations. Acceptability of each model to predict the medium and slow formulations was determined using ±20% as the limit for acceptable relative prediction error. When the best dissolution models were used, models 1 and 2 each failed to adequately predict Cmax for slow formulation (−26.8% error for model 1 and −20.4% error for model 2). However, the less appropriate model 3 adequately predicted Cmaxfor slow formulation (−15.1% error). The selection of the dissolution model also determined the outcome of IVIVC analysis, again with a less appropriate model resulting in successful prediction. When the Weibull function was used to characterize dissolution, model 2 failed to adequately predict Cmax for slow formulation (−20.4% error); however, model 2 adequately predicted Cmax for slow formulation when dissolution was characterized using the poorer fitting first-order model (−14.4% error). These results indicate that the success or failure of external validation of these metoprolol tartrate tablets was dependent on the pharmacokinetic and the dissolution models employed. Considering the role of subjectivity in identifying pharmacokinetic and dissolution models, these findings suggest a need to develop objective criteria to identify models a priori to IVIVC analysis.

Methods to Compare Dissolution Profiles and a Rationale for Wide Dissolution Specifications for Metoprolol Tartrate tablets

The objectives of this work were to apply several profile comparison approaches to dissolution data of four different but bioequiva-lent metoprolol tartrate tablet formulations to (1) identify the advantages and disadvantages of each approach, (2) quantify the metric for comparing dissolution profiles of each method, (3) determine metric limits that are consistent with the observed bioequivalence, and (4) rationalize the observed metric limits with respect to the role of dissolution in overall metoprolol absorption. Dissolution was performed by the USP monograph method on four formulations of metoprolol tartrate tablets (Lopressor plus fast, medium, and slow dissolving test formulations). Three general approaches to compare dissolution profiles were examined; they were ANOVA-based, model-independent, and model-dependent approaches. It is concluded that model-independent approaches and several model-dependent approaches yielded numerical results that can serve as objective and quantitative metrics for comparing entire dissolution profiles of the four metoprolol tartrate formulations. However, these methods presented complications. Some metrics were dependent on the length of the dissolution profile and the sampling scheme. Results from the pairwise procedures also depended on the pairing assignment of individual profiles. In spite of complications, these methods suggested wide dissolution specification limits. Wide dissolution specifications were rationalized through an analysis of in vitro–in vivo relationships, which indicated metoprolol dissolution from these formulations was not the rate-limiting step; hence, a range of dissolution profiles can be expected to yield equivalent plasma profiles.

Determination of Metoprolol Tartrate as Cu(II)-Dithiocarbamate Complex

An HPLC method has been developed for the determination of the beta adrenergic blocking drug metoprolol tartrate. The method is based on the formation of a Cu (II) - dithiocarbamate complex by precolumn derivatization of secondary amino group of metoprolol with CS2 and CuCl2 in the presence of ammonia. The complex is extracted into chloroform and injected into the chromatograph. Chromatographic separation was performed by a RP (μ Bondapak C18) column with methanol - pH 5.8 phosphate buffer (80 : 20) as the isocratic mobile phase. A variable wavelength absorbance detector (λ = 275 nm) was used. A linear relationship was obtained between peak areas and metoprolol tartrate concentrations over the range of 35 - 180 nmol ml−1. The method was applied to the analysis of metoprolol tartrate tablets and the results were statistically compared with those obtained by official method using t - and F - tests.

Evaluation of in Vitro Release Rate and in Vivo Absorption Characteristics of Four Metoprolol Tartrate Immediate-Release Tablet Formulations

ABSTRACTThe purpose of this investigation was to examine the impact of formulation and process changes on dissolution and bioavailability/bioequivalency of metoprolol tartrate tablets manufactured using a high-shear granulation process. A half-factorial (24-1, Res TV) design was undertaken to study the selected formulation and processing variables during scale-up. Levels and ranges for excipients and processing changes studied represented level 2 or greater changes as indicated by the SUPAC-IR Guidance. Blend and tableting properties were evaluated. Changes in sodium starch glycolate and magnesium stearate levels, and the order of addition microcrystalline cellulose (intra- vs. extragranular) were significant only in affecting percent drug released (Q) in 5,10, and 15 min. Statistical analysis of data showed no significant curvature. No interaction effects were found to be statistically significant. To examine the impact of formulation and processing variables on in vivo absorption, three batches were selected for a bioavailability study based on their dissolution profiles. Subjects received four metoprolol treatments (Lopressor®, slow-, medium-, and fast-dissolving formulations) separated by 1 week according to a randomized crossover design. After an overnight fast, subjects were administered one tablet (100 mg), blood samples were collected over 24 hr and plasma samples were analyzed. The formulations were found to be bioequivalent with respect to the log Cmax and log AUC0-∞. The results of this study suggest that: (i) bioavailability/bioequivalency studies may not be necessary for metoprolol tartrate and perhaps other class 1 drugs after level 2 type changes and (ii) in vitro dissolution tests may be used to show bioequivalence of metoprolol formulations with processing or formulation changes within the specified level 2 ranges for the equipment examined.

Methods to Compare Dissolution Profiles

The objective of this work was to apply several profile comparison approaches to dissolution data of four different Metoprolol tartrate tablet formulations in order to quantify each method's metric for comparing dissolution profiles. Dissolution was performed using the United States Pharmacopeia (USP) monograph method on four formulations of metoprolol tartrate tablets. Two general approaches to compare dissolution profiles were examined: model-independent approaches and model-dependent approaches. The model-independent methods included ANOVA-based procedures, ratio test procedures, and pair-wise procedures. The model-dependent approaches included zero-order, first-order, Hixson-Crowell, Higuchi, quadratic, Weibull, Gompertz, and logistic models. It is concluded that the ratio test procedures, the pair-wise procedures, and several model-dependent approaches yielded numerical results which can possibly serve as objective and quantitative metrics for comparing entire dissolution profiles of the four metopro...