Esomeprazole Magnesium Trihydrate Research Articles

Evaluating the Antimicrobial Activity of Esomeprazole Magnesium Trihydrate on Antibiotic-Resistant Bacteria Using Efflux Pumps

BACKGROUND: Antibiotic resistance mediated by efflux pumps is a serious public health threat. Esomeprazole magnesium trihydrate (EMT) is a proton pump inhibitor with reported antimicrobial activity, but its effects against efflux-mediated resistance are unknown. OBJECTIVE: To evaluate the antimicrobial activity of EMT alone and in combination with the efflux pump inhibitor reserpine against clinical isolates of _Pseudomonas aeruginosa, Acinetobacter baumannii_ and _Staphylococcus aureus_. METHODS: Minimum inhibitory concentration (MIC) assays were performed using the broth microdilution method on 15 non-duplicate clinical isolates and reference strains with/without EMT and reserpine. RESULTS: EMT demonstrated activity against all isolates, with MIC ranges of 4-32 μg/mL, 8-64 μg/mL and 2-16 μg/mL respectively. EMT MICs decreased 4-8-fold for 13/15 isolates when combined with reserpine, indicating EMT may inhibit efflux pumps. Similar reductions occurred for comparator antibiotics. CONCLUSIONS: This study provides the first evidence that EMT possesses intrinsic antimicrobial activity against these pathogens and may function as both an efflux pump substrate and inhibitor. EMT warrants further investigation as a potential adjuvant antibiotic for overcoming efflux-mediated resistance.

Formulation and evaluation of esomeprazole magnesium trihydrate controlled release floating tablets

Formulation and evaluation of esomeprazole magnesium trihydrate controlled release floating tablets

Application of Analytical Tools and Techniques for Estimation of a Proton Pump Inhibitor (Esomeprazole Magnesium Trihydrate): A Comprehensive Review

Abstract: The application of various sophisticated analytical tools and techniques is essential for estimating an active pharmaceutical ingredient present in either biofluids or pharmaceutical dosage forms. Reporting the multiple analytical methods used to quantify esomeprazole magnesium trihydrate, a proton pump inhibitor, is the ultimate goal of this review article. This article deals with a detailed discussion of different reported analytical procedures along with their pros and cons and their relevant criteria for quantifying the drug. Various analytical techniques like UV-Visible spectrophotometry, HPLC, HPTLC, hyphenated techniques, etc., are developed to assess the esomeprazole magnesium trihydrate in bulk materials, different pharmaceutical formulations, and biological matrices. Literature survey confirmed that the hyphenated techniques and chromatographic techniques are the best tools for biological matrices. Spectroscopic methods like UV and visible techniques are widely used for pharmaceutical matrices. All of the reported methods are accurate, precise, costeffective, and sensitive.

Assessment of the Proton Pump Inhibitor, Esomeprazole Magnesium Hydrate and Trihydrate, on Pathophysiological Markers of Preeclampsia in Preclinical Human Models of Disease.

Previously, we demonstrated that the proton pump inhibitor, esomeprazole magnesium hydrate (MH), could have potential as a repurposed treatment against preeclampsia, a serious obstetric condition. In this study we investigate the difference in the preclinical effectiveness between 100 µM of esomeprazole MH and its hydration isomer, esomeprazole magnesium trihydrate (MTH). Here, we found that both treatments reduced secretion of sFLT-1 (anti-angiogenic factor) from primary cytotrophoblast, but only esomeprazole MH reduced sFLT-1 secretion from primary human umbilical vein endothelial cells (assessed via ELISA). Both drugs could mitigate expression of the endothelial dysfunction markers, vascular cell adhesion molecule-1 and endothelin-1 (via qPCR). Neither esomeprazole MH nor MTH quenched cytotrophoblast reactive oxygen species production in response to sodium azide (ROS assay). Finally, using wire myography, we demonstrated that both compounds were able to induce vasodilation of human omental arteries at 100 µM. Esomeprazole is safe to use in pregnancy and a candidate treatment for preeclampsia. Using primary human tissues and cells, we validated that esomeprazole is effective in enhancing vascular relaxation, and can reduce key factors associated with preeclampsia, including sFLT-1 and endothelial dysfunction. However, esomeprazole MH was more efficacious than esomeprazole MTH in our in vitro studies.

Bulk Solution Assay Test Procedure Development and validation for Esomeprazole Sodium Injection 40mg as a CPP

Assay analytical test procedure at the Bulk-Solution stage for Esomeprazole Sodium Injection 40mgas a Critical Processing Parameters during manufacturing developed and validated. As per current available literature and the references, Esomeprazole active substance is available in market in the five forms, i.e. Esomeprazole as Plain [Tablet]; Esomeprazole Magnesium Trihydrate [Tablet, Capsule Delayed Release]; Esomeprazole Potassium [Tablet and Capsule]; Esomeprazole Strontium [Capsule Delayed Release] and Esomeprazole Sodium [Injectable].Assay test procedure for Active and other dosage forms [Tablet, Capsule] were available based on either Potentiometric Titration or HPLC basis. Product Esomeprazole Sodium Injection 40mg is not available in official pharmacopeia. As per available reference and literature assay test method for intermediate testing and finished product is based on HPLC. Intermediate testing [In-Process Testing] required as Critical Process Parameters [CPP] to ensure the quality i.e. appropriate bulk-solution purity, before to proceed for filtration and filling of Bulk-solution in unit dosage form [Vials]. To test the bulk solution purity approximate 5-6 hours required by HPLC. Which leads to hold the Bulk solution, further it impact and may risk to Bio-Burden of bulk solution. Also it impact and reduce the productivity of line by 5-6 hours. HPLC testing required special skilled manpower and cost. Considering all above concerns Study carried for test method development based on UV-Spectroscopy, HPLC and potentiometric titration. Based on method validation performed for UV-Spectrometry, HPLC and potentiometric titration; Test procedure developed and validated based on UV-Spectrometry is found Simple, Accurate, Precise, Economical and Rapid to save time and cost with increase in productivity as a Critical Processing Parameters for Esomeprazole Sodium Injection 40mgat the Bulk-Solution stage during manufacturing.

Development and Characterization of Oral Nanosuspension Using Esomeprazole Magnesium Trihydrate

Background: Nanosuspension has arisen as a lucrative, remunerative, as well as a potent approach to improve the solubility and dissolution rate of poorly soluble drug entities. Several challenges are still present in this technology which need more research. Objective: The prime aim of this research work is to develop, optimize and characterize the oral nanosuspension using esomeprazole magnesium trihydrate as a drug candidate. Methods: The drug nanosuspensions were prepared using both approaches; Top-down and Bottom-up as the combinational approach. Poloxamer 188 was used as a stabilizer in this study. All the important formulation variables, like concentration of stabilizers that may influence characteristics of the nanosuspensions, were optimized. Formulation screening was performed using the optimization process, and the optimized nanosuspension was evaluated for its particle size, polydispersity index, zeta potential, shape, in vitro drug release and stability. Results: For optimization of drug nanosuspension, the effect of Poloxamer 188 concentration and esomeprazole concentration was investigated and the optimal values were 0.3% w/v and 4 mg/ml, respectively. The particle size of nanosuspensions was in the range of 185 to 1048 nm with varying the zeta potential values from -11.2 to -27.5 mV. The in vitro dissolution rate of esomeprazole was increased up to 3-folds, approximately (92% in 90 min) as compared with crude esomeprazole drug (31% in 90 min) due to the decrease in particle size. Conclusion: The result indicated that the combination of top-down and bottom-up approach used for preparing the oral nanosuspension is a suitable approach for poorly aqueous soluble drug moieties like esomeprazole magnesium.

Development and validation of high performance liquid chromatographic method for the determination of esomeprazole in tablets

A simple, selective and accurate high performance liquid chromatographic (HPLC) method was developed and validated for the analysis of esomeprazole magnesium trihydrate (ES) in tablets. Chromatographic separation was achieved isocratically on a C18 column utilizing a mobile phase of acetonitrile/phosphate buffer (60:40, v/v, pH 7) at a flow rate of 1.0 mL/min with UV detection at 205 nm. Lansoprazole was used as an internal standard (IS). The calibration curve of ES was linear in the range of 100-1000 ng/mL (r = 0.9992, n = 4). The RSD values for intra- and inter-day precision were 0.66-0.86% and 0.84-1.11%, respectively. The proposed method was successfully applied to the determination of ES in tablets. The mean recovery for ES from the tablets ranged between 97.82-98.22%. ES was subjected to neutral, acid and alkali hydrolysis as well as oxidation, dry heat treatment and photodegradation. Being simple, accurate and selective, the method can be used for routine quality control analysis.

Development and Validation of Stability Indicating Method for Simultaneous Estimation of Esomeprazole and Levosulpiride by HPTLC using Experimental Design

The present study examines simultaneous multiple response optimization using desirability function for the development of an HPTLC method to detect esomeprazole magnesium trihydrate and levosulpiride in pharmaceutical dosage form. HPTLC separation was performed on aluminium plates pre-coated with silica gel 60 F254 as the stationary phase using ethyl acetate:methanol:toluene:ammonia (7:1.5:1.5:0.1% v/v/v) as the mobile phase. Full factorial design applied for the optimization of degradation condition. Esomeprazole magnesium trihydrate and levosulpiride were subjected to acid, alkali hydrolysis, oxidation and photodegradation. Experimental full factorial design has been used during forced degradation to determine significant factors responsible for degradation and to optimize degradation conditions reaching maximum degradation. 32 and 23 full factorial design has been used for optimization of chromatographic condition in acid and base degradation study, respectively. Quantification was achieved based on a densitometric analysis of esomeprazole magnesium trihydrate and levosulpiride over the concentration range of 800-4000 ng/band and 1500-7500 ng/band, respectively at 254 nm. The method yielded compact and well-resolved bands at Rf of 0.70 ± 0.02 and 0.32 ± 0.02 for esomeprazole magnesium trihydrate and levosulpiride, respectively. The linear regression analysis for the calibration plots produced r2 = 0.9967 and r2 = 0.9981 for esomeprazole magnesium trihydrate and levosulpiride, respectively. Method is validated as per ICH (Q2)R1 guideline.

Development and Validation of Genotoxic Impurity in Esomeprazole Magnesium Trihydrate Active Pharmaceutical Ingredient by LC-MS/MS

Development and Validation of Genotoxic Impurity in Esomeprazole Magnesium Trihydrate Active Pharmaceutical Ingredient by LC-MS/MS

Lek Esomeprazole Magnesium Trihydrate kao potencijalni neotrovni inhibitor korozije za meki čelik u kiselim medijima

The inhibiting effect of Esomeprazole Magnesium Trihydrate drug on the corrosion of mild steel (MS) in 1 M HCl was performed by chemical tests (weight loss (WL)) and electrochemical methods (Tafel polarization (TP), electrochemical frequency modulation (EFM) and AC impedance spectroscopy (EIS)). The adsorption isotherm of Esomeprazole Magnesium Trihydrate drug on the MS surface was found to follow Temkin adsorption isotherm. Some thermodynamic parameters were computed and discussed. The obtained data showed that the inhibition efficiency (IE) rises with increasing the dose of the Esomeprazole Magnesium Trihydrate and with raising the temperature. The morphology of MS surface was analyzed by using scanning electron microscope (SEM), atomic force microscopy (AFM), and Fourier transforms infrared spectroscopy (FTIR) techniques. All test methods were in good agreement with each other.

Validation of Esomeprazole Magnesium Tri-hydrate in Pharmaceutical dosage form by RP-HPLC Method

Validation of Esomeprazole Magnesium Tri-hydrate in Pharmaceutical dosage form by RP-HPLC Method

UV Derivative Spectrophotometric Methods for validation of Esomeprazole Magnesium tri-hydrate in Bulk and Pharmaceutical Dosage Form

The objective of the study was to develop simple, accurate, precise and rapid UV first and second order derivative spectrophotometric methods with subsequent validation by using ICH guidelines for the determination of Esomeprazole magnesium tri-hydrate in pharmaceutical dosage form. The proposed first and second order derivative methods involve the measurement of absorbance of drug at 293 nm and 281 nm for the estimation of Esomeprazole magnesium tri-hydrate respectively. The linearity of the proposed methods were found in the concentration range of 4-40 µg /ml (r2= 0.9999) for first order and second order derivative methods and the percentage mean recovery was found to be 99.59 % to 100.69 % respectively. The methods were also statistically validated for its linearity, accuracy and precision. Both intra and inter day variation showed less percentage (%) RSD values indicating high grade of precision of these methods.

Esomeprazole ameliorates CCl4 induced liver fibrosis in rats via modulating oxidative stress, inflammatory, fibrogenic and apoptotic markers

Background: Hepatic fibrosis is a major health problem that requires further medical attention. Proton pump inhibitors are proven to possess other therapeutic potentials apart of their acid anti-secretory actions. Aim of the work: To test possible anti-fibrotic effect of esomeprazole magnesium trihydrate in management of liver fibrosis compared to silymarin, the well-known hepatoprotective agent. Materials & Methods: 40 male albino rats were divided into 4 groups: normal control group; CCl4-treated group (1 mL/kg 40% CCl4, diluted in olive oil) I.P twice weekly for 6 weeks; esomeprazole-treated group (30 mg/kg body weight); and Silymarin-treated group (100 mg/kg body weight). Both esomeprazole and silymarin were given orally daily for two weeks after the last CCl4 dose. Serum and tissue samples were assessed for histopathological and biochemical analyses. Results: Esomeprazole reversed hepatocellular damage, improved liver integrity, corrected major histopathological disturbances induced by CCl4 and lowered fibrosis scoring. It also improved anti-oxidant capacity and attenuated lipid peroxidation. Esomeprazole treatment resulted in down-regulation of hepatic pro-apoptotic Bax and up-regulation of anti-apoptotic Bcl2 protein expressions. In addition, it resulted in inhibition of TNF-α, TGF-β and IL-6 -mediated inflammatory responses, and retrieval of the epithelial marker e-cadherin. Conclusion: Esomeprazole confers significant anti-fibrotic actions. Further study is needed to elucidate other probable mechanisms for this effect and to test their anti-fibrotic potential clinically.

Analysis of 2-Week Data from Two Randomized, Controlled Trials Conducted in Subjects with Frequent Heartburn Treated with Esomeprazole 20 mg

PurposeThese secondary analyses used data from 2 similarly designed studies in subjects experiencing frequent heartburn to evaluate the efficacy of esomeprazole 20 mg once daily for 2 weeks, which reflects the approved over-the-counter dosage and duration. MethodsSubjects without endoscopically identified erosive esophagitis who were experiencing heartburn for ≥6 months and ≥4 of 7 days prior to baseline (study 1, N = 368; study 2, N = 349) were randomly assigned to receive double-blind treatment with esomeprazole 40 or 20 mg (administered as esomeprazole magnesium trihydrate 44.5 and 22.3 mg, respectively) or placebo once daily for 4 weeks. Subjects recorded the severity of heartburn in a daily diary, and investigators assessed subjects at each study visit. Two-week assessments were the primary end points of interest in these analyses and included the percentage of subjects with complete heartburn resolution (no episodes during 7 consecutive days), time to sustained complete heartburn resolution (the first of 7 consecutive episode-free days), and heartburn relief (no episodes other than ≤1 mild episode during 7 consecutive days). FindingsAt week 2, the percentages of subjects who experienced complete heartburn resolution were significantly greater with esomeprazole 40 mg (study 1, 26.1%; study 2, 35.3%) and 20 mg (study 1, 25.2%; study 2, 35.7%) compared with placebo (study 1, 9.0%; study 2, 3.4%) (all, P ≤ 0.001). Beginning on day 1, the percentages of subjects who experienced sustained heartburn resolution was significantly greater in the groups treated with esomeprazole 40 mg (study 1, 19%; study 2, 19%; P < 0.0001) and 20 mg (study 1, 10%; study 2, 15%; P < 0.05) compared with the group that received placebo (study 1, 2%; study 2, 1%). Additionally, at week 2, the percentages of subjects experiencing heartburn relief were significantly greater with esomeprazole 40 mg (study 1, 35.3%; study 2, 40.5%) and 20 mg (study 1, 34.5%; study 2, 46.4%) compared with placebo (study 1, 16.5%; study 2, 8.6%) (all, P ≤ 0.001). ImplicationsThe results of this study demonstrate that once-daily treatment with esomeprazole 20 mg for 2 weeks effectively resolved subjects׳ heartburn compared with placebo, beginning on day 1. Studies precede FDA Act 801 clinical trial registration and results submission requirements.

Area under Curve Spectrophotometric Estimation of Esomeprazole Magnesium Tri-Hydrate in Bulk Drug and Pharmaceutical Dosage Form

A simple and precise UV-spectrophotometric method, area under curve [AUC], has been developed and validated for the estimation of esomeprazole magnesium tri-hydrate in bulk drug and its pharmaceutical formulation. Esomeprazole magnesium tri-hydrate was estimated by area under curve (AUC) method for the zero and first order spectrums in between 297 to 305nm and 286 nm to 296 nm respectively. Beer's law was obeyed in the concentration range of 1 to 40 μg/ml with coefficient of correlation value 0.9999. These methods were tested and validated for various parameters according to ICH guidelines. The precision expressed as relative standard deviation, which was within the range of 0.38947% to 0.94355% for the above methods. The proposed methods were successfully applied for the determination of esomeprazole magnesium tri-hydrate in pharmaceutical formulation. Results of the analysis were validated statistically and were found to be satisfactory. The proposed methods are simple, easy to apply, low-cost and require relatively inexpensive instruments.

FORMULATION, OPTIMIZATION, CHARACTERIZATION AND IN VIVO ANTI-ULCER ACTIVITY OF ESOMEPRAZOLE MAGNESIUM TRIHYDRATE GASTRORESISTANT MICROSPHERES

&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The objective of the present investigation was to prepare gastro-resistant microspheres of esomeprazole magnesium trihydrate (EMT) to prevent its degradation in the acidic environment of the stomach and enhance its bioavailability via intestinal absorption.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;EMT loaded gastro-resistant microspheres were prepared using hypromellose acetate succinate (HPMCAS) as the gastro-resistant polymer by ‘non-aqueous solvent evaporation’ technique. A 3-factor 3 level factorial design was used to optimise EMT: HPMCAS ratio, the concentration of Span 80 and stirring speed with respect to percent entrapment efficiency and particle size. Further characterization was carried out using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), &lt;em&gt;In vitro&lt;/em&gt; release study and &lt;em&gt;In vivo&lt;/em&gt; anti-ulcer activity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Fourier transform infrared &lt;strong&gt;(&lt;/strong&gt;FTIR) study indicated compatibility between drug and polymer. DSC study revealed that the drug was molecularly dispersed in the polymer. The optimised batch showed 49.63±1.23% drug entrapment and 170.12±3.36 μm particle size. SEM study showed that microspheres were spherical in shape&lt;strong&gt;. &lt;/strong&gt;&lt;em&gt;In vitro&lt;/em&gt; drug release study showed only 4.28±1.23% drug release in simulated gastric media in 2 hr and 93.46±1.20% release in simulated intestinal media after 1 hr from the optimised batch.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Results of &lt;em&gt;in vitro &lt;/em&gt;release studies indicated the gastro-resistant nature of the developed microspheres. &lt;em&gt;In vivo&lt;/em&gt; anti-ulcer activity demonstrated that EMT loaded microspheres were able to significantly reduce ethanol-induced ulcer formation in rats’ stomach as compared to the aqueous solution of EMT. So it can be concluded that the developed gastro-resistant microspheres of EMT prevented drug release in the stomach which would lead to a significant improvement in its bioavailability through enhanced intestinal absorption&lt;/p&gt;

Fabrication and in vitro evaluation of novel pH‐sensitive poly (2‐methoxyethyl methacrylate‐co‐itaconic acid) microgels

AbstractThe present work focused on the synthesis and evaluation of cross‐linked poly(2‐methoxyethyl methacrylate‐co‐itaconic acid) [p(MEMA‐co‐IA)] microgels for controlled and extended drug delivery, in an attempt to improve the bioavailability of the drugs and to get maximum therapeutic benefits. A series of p(MEMA‐co‐IA) microgels were prepared by modified free‐radical suspension polymerization using ethylene glycol dimethacrylate as cross‐linker. Characterization was performed through FTIR, TGA, DSC, XRD, DLS and SEM. pH responsiveness was evaluated by equilibrium swelling studies in phosphate buffer solutions of different pH values (pH 1.2, 4, 6.5, and 7.4) with constant ionic strength. To demonstrate the potential use of microgels for drug delivery, esomeprazole magnesium trihydrate (EMT) was loaded as model drug and in vitro dissolution studies were performed. FTIR and thermal analysis confirmed the formation of cross‐linked p(MEMA‐co‐IA) microgels. XRD indicated dispersion of drug into the network at molecular level. SEM illustrated smooth, round and uniformly distributed microspheres. A remarkably higher swelling at higher pH values (pH 6.5 and 7.4) compared to pH 1.2 demonstrated the pH‐responsive nature of the microgels. All the formulations showed pH‐dependent drug release following Higuchi with non‐fickian mechanism of drug diffusion. In light of the results obtained from this study, it was concluded that p(MEMA‐co‐IA) microgels have potential to release drug in controlled manner responsive to pH of the external environment.

Identifying Clinical Predictors of Heartburn Resolution With Over-the-Counter Esomeprazole

Introduction: Identifying factors associated with complete resolution of heartburn (HB) during treatment may help set appropriate expectations for the use of over-the-counter (OTC) proton-pump inhibitor therapy for frequent HB. These analyses were conducted to determine patient-level factors related to HB resolution during treatment with esomeprazole (ESO) at the approved OTC dose/duration. Methods: Data were pooled from the first 14 days in subjects with frequent HB randomly assigned to double-blind treatment with ESO 20 mg (n=921; administered as 22.3 mg esomeprazole magnesium trihydrate) or placebo (n=909) in 6 similarly designed studies conducted at US study centers. Subjects recorded HB episodes in daily diaries throughout the 14-day treatment period. Multivariate analyses were conducted to identify predictors of complete HB resolution, defined as no 24-hour HB for 7 consecutive days. The following clinical predictors were assessed using a stepwise logistic regression adjusted for study: treatment, study site, age (as a continuous variable), gender, race, pre-treatment HB frequency, and the occurrence of HB during treatment. Additional analyses explored alternate endpoints, including complete resolution of daytime and nighttime HB episodes for 7 consecutive days, and other predictive variables only available in subsets of the overall data set. Pre-treatment HB frequency was primarily ≥2 days/week; mean age was 45.5 years (range: 18-90 years). Results: Treatment with ESO (p < .0001), age (p=.0006), nighttime HB during treatment (p < .0001), and lower pre-treatment HB frequency (p < .0001) were significant predictors of complete resolution of 24-hour HB. Significant predictors of complete resolution of daytime HB (4 studies) were treatment with ESO, age, nighttime HB during treatment, and lower pre-treatment daytime HB frequency (p < .0001 for all). Treatment with ESO, age, frequency of pre-treatment nighttime HB, and daytime HB during treatment were predictors of complete resolution of nighttime HB (p < .0001 for all). Conclusion: Patient factors associated with complete resolution of HB with ESO 20 mg included increasing age, absence of nighttime HB during treatment, and less-frequent pre-treatment HB.

Rat pre- and postnatal development study with esomeprazole magnesium trihydrate: Lack of F1 bone effects

Rat pre- and postnatal development study with esomeprazole magnesium trihydrate: Lack of F1 bone effects

Rat pre- and postnatal development study with esomeprazole magnesium trihydrate: Lack of F1 bone effects

Rat pre- and postnatal development study with esomeprazole magnesium trihydrate: Lack of F1 bone effects