-
Spectrochimica Acta. Part A, Molecular... Dec 2023The aim of this study is to develop and validate two simple spectrophotometric methods for simultaneous determination of metoprolol succinate (MET) and olmesartan...
Area under the curve and ratio difference spectrophotometric methods with evaluation of the greenness for simultaneous determination of olmesartan medoxomil and metoprolol succinate.
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 spectrophotometricmethod. 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.
Topics: Olmesartan Medoxomil; Metoprolol; Spectrophotometry
PubMed: 37499475
DOI: 10.1016/j.saa.2023.123164 -
Luminescence : the Journal of... Dec 2023The present research has established a quick and highly sensitive second-derivative synchronous fluorometric technique for the simultaneous quantification of a binary...
A novel sustainable second-derivative synchronous spectrofluorimetric method for the simultaneous determination of olmesartan medoxomil and rosuvastatin calcium in bulk and formulations: Integrated greenness and whiteness evaluation.
The present research has established a quick and highly sensitive second-derivative synchronous fluorometric technique for the simultaneous quantification of a binary mixture of olmesartan medoxomil and rosuvastatin calcium. Simultaneously, the suggested approach was used to detect the synchronous fluorescence intensity of the cited drugs at Δ λ = 80 nm in ethanol to determine the concentrations of olmesartan medoxomil and rosuvastatin calcium at 265 and 240 nm, respectively. Various experimental conditions were tested, and each variable was analyzed and optimized. The calibration graphs were shown to be linear within ranges of 0.1-2.0 and 0.5-6.0 μg ml for each drug concentration, respectively. The newly developed Green Solvents Selecting Tool (GSST) was utilized to assess the solvent's sustainability. Furthermore, the proposed method was found to be environmentally friendly after being evaluated with three different tools [the Green Analytical Procedure Index (GAPI), the Analytical Greenness Metric (AGREE), and the Analytical Eco-Scale with Eco-score equal to 95]. The whiteness qualities were also studied using the Red-Green-Blue (RGB12) model, which was recently designed and showed a high score equal to 92.9. The proposed method's good findings, as well as its ongoing sustainability, simplicity, and economy, stimulate its application in QC laboratories.
PubMed: 38062646
DOI: 10.1002/bio.4641 -
Scientific Reports May 2023In recent years, the outbreak of infectious disease caused by Zika Virus (ZIKV) has posed a major threat to global public health, calling for the development of...
In recent years, the outbreak of infectious disease caused by Zika Virus (ZIKV) has posed a major threat to global public health, calling for the development of therapeutics to treat ZIKV disease. Several possible druggable targets involved in virus replication have been identified. In search of additional potential inhibitors, we screened 2895 FDA-approved compounds using Non-Structural Protein 5 (NS5) as a target utilizing virtual screening of in-silco methods. The top 28 compounds with the threshold of binding energy -7.2 kcal/mol value were selected and were cross-docked on the three-dimensional structure of NS5 using AutoDock Tools. Of the 2895 compounds screened, five compounds (Ceforanide, Squanavir, Amcinonide, Cefpiramide, and Olmesartan_Medoxomil) ranked highest based on filtering of having the least negative interactions with the NS5 and were selected for Molecular Dynamic Simulations (MDS) studies. Various parameters such as RMSD, RMSF, Rg, SASA, PCA and binding free energy were calculated to validate the binding of compounds to the target, ZIKV-NS5. The binding free energy was found to be -114.53, -182.01, -168.19, -91.16, -122.56, and -150.65 kJ mol for NS5-SFG, NS5-Ceforanide, NS5-Squanavir, NS5-Amcinonide, NS5-Cefpiramide, and NS5-Ol_Me complexes respectively. The binding energy calculations suggested Cefpiramide and Olmesartan_Medoxomil (Ol_Me) as the most stable compounds for binding to NS5, indicating a strong rationale for their use as lead compounds for development of ZIKV inhibitors. As these drugs have been evaluated on pharmacokinetics and pharmacodynamics parameters only, in vitro and in vivo testing and their impact on Zika viral cell culture may suggest their clinical trials on ZIKV patients.
Topics: Humans; Zika Virus; Zika Virus Infection; Protein Binding; Methyltransferases; Drug Repositioning; Viral Nonstructural Proteins; Antiviral Agents
PubMed: 37188743
DOI: 10.1038/s41598-023-33341-6 -
Journal of Clinical Hypertension... May 2021Angiotensin-receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin-receptor blockers may be more... (Meta-Analysis)
Meta-Analysis
Is the newest angiotensin-receptor blocker azilsartan medoxomil more efficacious in lowering blood pressure than the older ones? A systematic review and network meta-analysis.
Angiotensin-receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin-receptor blockers may be more effective than the older ones. A network meta-analysis was performed to compare the efficacy of various angiotensin-receptor blockers in reducing office and ambulatory blood pressure in hypertensive patients. Relevant literature was searched from English and Chinese databases for randomized controlled trials involving angiotensin-receptor blockers in hypertension. Efficacy variables included systolic and diastolic blood pressure either in the office or on ambulatory blood pressure monitoring. Absolute blood pressure reductions at 6-12 weeks of treatment and their credible intervals were reported. A total of 34 publications provided adequate data for analysis (n = 14 859). In 28 studies on office systolic blood pressure (n = 12 731), against the common comparator valsartan 80 mg, the differences in systolic blood pressure were in favor of azilsartan medoxomil (20-80 mg), irbesartan (300 mg), olmesartan (20-40 mg), telmisartan (80 mg), and valsartan (160-320 mg), but not candesartan (8-16 mg), losartan (50-100 mg), irbesartan (150 mg), olmesartan (10 mg), and telmisartan (40 mg). The ranking plot shows that azilsartan medoxomil 80 mg had a possibility of 99% being the best in the class. Similar results were observed for office diastolic blood pressure and from 13 studies for 24-hour ambulatory systolic and diastolic blood pressure. In conclusion, angiotensin-receptor blockers had different blood pressure lowering efficacy. The newest angiotensin-receptor blocker azilsartan medoxomil at the dose of 80 mg seemed to be most efficacious in reducing both systolic and diastolic blood pressure in the office and on ambulatory measurement.
Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensins; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Humans; Hypertension; Network Meta-Analysis; Olmesartan Medoxomil; Oxadiazoles; Tetrazoles
PubMed: 33609077
DOI: 10.1111/jch.14227 -
Turkish Journal of Pharmaceutical... Mar 2023Olmesartan medoxomil (OLM) and metoprolol succinate (MPS) in fixed-dose combination (FDC) tablet formulation prescribed extensively. Stability indicating (SI) method for...
OBJECTIVES
Olmesartan medoxomil (OLM) and metoprolol succinate (MPS) in fixed-dose combination (FDC) tablet formulation prescribed extensively. Stability indicating (SI) method for impurities and related substance (RS) test quantitates the amount of these analytes in formulation; the manuscript presents SI/RS-ultra-high performance liquid chromatography-photodiode array (UHPLC-PDA) method for OLM and MPS and their impurities.
MATERIALS AND METHODS
Well-resolved separation of all analytes was achieved with gradient elution on a Shimadzu on Shimpack GIST-C18 (100 mm x 2.1 mm, 2 µm) column maintained at 25°C. Mobile phase-A consist of 0.1% orthophosphoric acid in water and mobile phase-B was acetonitrile at a flow rate of 0.4 mL/min, data integrated at 225 nm and 16 min of short runtime for satisfactory elution of all peaks.
RESULTS
The proposed SI/RS-UHPLC-PDA method was developed and validated as International Conference on Harmonisation (ICH) of Technical Requirements guidelines. The system suitability test complied by all eluted peaks of the interest with acceptable linearity, recovery, and precision. Specificity, robustness, and method sensitivity parameters were determined; all the parameters were found to be within the limits. All the impurities and stress-degraded peaks were well resolved.
CONCLUSION
The proposed method was found to be simple, fast, linear, and accurate. Further, the method is precise, robust, and specific; suitable for routine IPQC during active pharmaceutical ingredient manufacturing, stability and impurity profiling studies of the titled bulk analytes. Furthermore, the method can be extended to assess the levels of impurities formed during life cycle of new FDCs of titled analytes.
PubMed: 36864594
DOI: 10.4274/tjps.galenos.2022.57384 -
Journal of AOAC International Mar 2022Few spectrophotometric methods have been developed for the simultaneous determination of atorvastatin calcium (ATO) and olmesartan medoxomil (OLM).
BACKGROUND
Few spectrophotometric methods have been developed for the simultaneous determination of atorvastatin calcium (ATO) and olmesartan medoxomil (OLM).
OBJECTIVE
This work aimed to develop and validate five simple spectrophotometric methods for the simultaneous estimation of ATO and OLM in their tablet form.
METHODS
Method I applied the area under curve (AUC) based on the measurement of areas between 241 and 261 nm for ATO, and 248 and 263 nm for OLM. Method II applied second derivative spectrophotometry where the analytical amplitudes at 246.5 and 235 nm were chosen for the estimation of ATO and OLM, respectively. Method III applied the ratio difference (RD) method based on the measurement of amplitude difference (ΔP) within ratio spectra; ΔP (240-260 nm) was directly related to ATO concentration, and ΔP (262-240 nm) was directly related to OLM concentration. Method IV depended on the absorbance ratio method in which the wavelength at the iso-absorptive point (λISP) and the maximum absorbance wavelength (λmax), 277 and 255.5 nm, respectively, were used to calculate OLM concentration, while ATO concentration was determined from the zero-order UV spectra at 300 nm. Method V utilized a dual wavelength (DW) technique where ΔA between 247.5 and 262 nm was directly related to ATO concentration, and ΔA between 216 and 238 nm was directly related to OLM concentration.
RESULTS
The results of the assays indicated good mean % recovery ± SD as well as good agreement with the reported method.
CONCLUSION
Five simple and rapid spectrophotometric methods were developed, validated, and successfully applied for simultaneous estimation of ATO and OLM tablets.
HIGHLIGHTS
None of the developed methods has previously been reported for simultaneous determination of ATO and OLM.
Topics: Atorvastatin; Drug Compounding; Olmesartan Medoxomil; Spectrophotometry; Tablets
PubMed: 34850012
DOI: 10.1093/jaoacint/qsab151 -
AAPS PharmSciTech Sep 2020Olmesartan medoxomil (OLM) an antihypertensive molecule with poor solubility and poor bioavailability (26% when taken orally) was selected as a model drug. Herein,...
Olmesartan medoxomil (OLM) an antihypertensive molecule with poor solubility and poor bioavailability (26% when taken orally) was selected as a model drug. Herein, rationale development of amorphous solid dispersion with hot-melt extrusion of poorly bioavailable OLM was carried out with the aid of quality by design (QbD), in-silico, in-vitro, and in-vivo evaluations. Polymer selection commenced with the selection of thermoplastic water-soluble polymers with the compatible processing temperature window as per the thermal behavior of OLM. Molecular dynamics (MD) simulations as well assisted in the selection of a carrier. Promising dissolution enhancement was observed with the help of Kollidon VA-64 (VA-64) as a carrier. Optimization of the formulation was executed using the QbD approach with design of experiment as a statistical optimization tool. Interactions between VA-64 and OLM on the atomic level were studied with the help of atomistic MD simulations. Characterization of the optimized extrudates were carried out with scanning electron microscopy, atomic force microscopy, differential scanning calorimetry, thermogravimetric analysis, Fourier transforms infrared spectroscopy, powder X-ray diffraction, in-vitro dissolution study, and in-vivo pharmacokinetic studies. Molecular-level mixing of OLM with VA-64 resulted into glass solution formation which rapidly dissolves (28 times in-vitro dissolution enhancement) in GI tract fluids and instantly gets absorbed into blood circulation. In-vivo pharmacokinetic studies performed in Sprague-Dawley rats reflected superior bioavailability (201.60%) with a significant increase in the C with short T through amorphization of OLM. The in-silico results were in agreement with the observed results of in-vitro dissolution studies and in-vivo pharmacokinetic study.
Topics: Administration, Oral; Animals; Antihypertensive Agents; Biological Availability; Calorimetry, Differential Scanning; Computer Simulation; Hot Melt Extrusion Technology; In Vitro Techniques; Olmesartan Medoxomil; Rats; Rats, Sprague-Dawley; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 32888102
DOI: 10.1208/s12249-020-01780-3 -
Computational and Mathematical Methods... 2021Ischemic stroke combined with hypertension can increase risks of stroke recurrence and death.
The Clinical Efficacy of Clopidogrel Bisulfate Tablets Combined with Olmesartan Medoxomil for Ischemic Stroke with Hypertension and the Effect of Angiotensin II Type 1 Receptor Level on Prognosis.
BACKGROUND
Ischemic stroke combined with hypertension can increase risks of stroke recurrence and death.
AIM
The aim of this study is to investigate the clinical efficacy of clopidogrel bisulfate tablets combined with olmesartan medoxomil in the treatment of ischemic stroke patients with hypertension and the effect of angiotensin II type 1 receptor (ATR) level on prognosis.
METHODS
Ninety ischemic stroke patients with hypertension were chosen for continuous treatment with clopidogrel bisulfate tablets and olmesartan medoxomil for 12 months. The Modified Edinburgh Scandinavian Stroke Scale (MESSS) score, Brunnstrom score, Barthel score, death, recurrence, and progression of cerebrovascular residual lesions were observed and recorded during the treatment period. According to the plasma ATR expression of the patients before treatment, the patients were divided into a high-ATR group and low-ATR group. Then, survival analysis was performed.
RESULTS
Compared with pretreatment, the MESSS scores of the patients at the first, second, third, sixth, ninth, and twelfth months after treatment were reduced ( < 0.01) while the Brunnstrom score and Barthel score were prominently boosted ( < 0.01). Compared with the low-ATR group, patients in the high-ATR group had higher rates of stroke recurrence and progression of residual cerebrovascular lesions ( < 0.05).
CONCLUSION
Clopidogrel bisulfate tablets combined with olmesartan medoxomil has prominent clinical effects in the treatment of ischemic stroke patients with hypertension, evidently improving the prognosis. In addition, the level of ATR may be a vital factor affecting the prognosis.
Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Clopidogrel; Computational Biology; Drug Therapy, Combination; Female; Humans; Hypertension; Ischemic Stroke; Male; Middle Aged; Olmesartan Medoxomil; Platelet Aggregation Inhibitors; Prognosis; Receptor, Angiotensin, Type 1; Treatment Outcome
PubMed: 34745325
DOI: 10.1155/2021/4487393 -
Pharmaceutical Development and... Jul 2022Hexadecane membrane-parallel artificial membrane permeability assay (HDM-PAMPA) is based on an artificial HDM that separates the two compartments (donor and acceptor...
Hexadecane membrane-parallel artificial membrane permeability assay (HDM-PAMPA) is based on an artificial HDM that separates the two compartments (donor and acceptor compartment). This model is used to predict the permeability of drugs in gastrointestinal tract and to simulate the passive absorption. behavior of the drugs can be estimated with these systems in drug development studies. In our study, we optimized HDM-PAMPA model to determine permeability of olmesartan medoxomil (OM) lipid based drug delivery system (OM-LBDDS). In order to prove that LBDDS formulation facilitates the weak permeability of OM, permeation rates were compared with the OM suspension formula (containing 0.25% carboxymethylcellulose). The experiment was performed on a 96-well MultiScreen® PAMPA filter plate (MAIPN4510). The permeability of olmesartan formulations from the donor to acceptor compartment separated by a HDM membrane were determined by the previous validated HPLC method. We created positive control series without coating HDM to present the LBDDS and suspension formulation permeability from uncoated plates. The effective permeability constant () was calculated by the formula and improvement of permeability of OM-LBDDS formulation from HDM was confirmed. On the contrary there was no permeation of OM-Suspension in the hexadecane coated plates. As a result, the intestinal permeability of OM-LBDDS was calculated to be at least 100 times more than the suspension. OM-Suspension permeation was only observed in the hexadecane uncoated positive control plates. This was also manifestation of HDM-PAMPA mimicking permeability of intestines because of its lipidic construction.
Topics: Alkanes; Carboxymethylcellulose Sodium; Lipids; Membranes, Artificial; Olmesartan Medoxomil; Permeability; Suspensions
PubMed: 35972198
DOI: 10.1080/10837450.2022.2114495 -
Circulation Reports Sep 2020Angiotensin II receptor blockers (ARBs) are widely used for the management of hypertension in Japan; however, comparative efficacy data within the ARB drug class remain...
Angiotensin II receptor blockers (ARBs) are widely used for the management of hypertension in Japan; however, comparative efficacy data within the ARB drug class remain limited. This systematic literature review identified randomized controlled trials (RCT) indexed in PubMed and Ichushi in Japanese patients with hypertension receiving ARB monotherapy (azilsartan, candesartan cilexetil, irbesartan, losartan potassium, olmesartan medoxomil, telmisartan, valsartan) in at least 1 arm. Of 763 RCTs identified, 77 met the eligibility criteria; of which, 37 reported mean change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline in the office setting and were used to construct the network. A fixed-effects model (FEM) showed the effect of each drug vs. the reference, azilsartan. Using the FEM, the mean (95% credible interval) change from baseline in SBP/DBP for candesartan cilexetil, irbesartan, losartan potassium, olmesartan medoxomil, telmisartan, and valsartan was 3.8 (2.9-4.8)/2.6 (2.0-3.1), 4.8 (2.0-7.5)/3.7 (1.8-5.6), 3.0 (0.8-5.1)/1.9 (0.5-3.3), 3.2 (1.2-5.1)/2.7 (1.3-4.1), 3.2 (0.8-5.6)/2.0 (0.3-3.6), and 3.1 (1.1-5.1)/2.4 (1.1-3.8) mmHg, respectively. The results of this meta-analysis provide evidence that azilsartan has a more favorable efficacy profile than the other ARBs in reducing SBP and DBP.
PubMed: 33693183
DOI: 10.1253/circrep.CR-20-0076