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Biomedical Chromatography : BMC Nov 2021The current work describes the development and validation of a stability-indicating UPLC method for the determination of olmesaratan medoxomil (OLM), amlodipine besylate...
Development and validation of a stability-indicating UPLC method for the determination of olmesartan medoxomil, amlodipine and hydrochlorothiazide degradation impurities in their triple-combination dosage form using factorial design of experiments.
The current work describes the development and validation of a stability-indicating UPLC method for the determination of olmesaratan medoxomil (OLM), amlodipine besylate (AMB), hydrochlorothiazide (HCT) and their degradation products in the triple-combination tablet dosage form. The separation was achieved using a Zorbax Eclipse plus C RRHD (100 mm × 3.0 mm), 1.8 μm column with gradient elution of mobile phase A containing 0.02 m of sodium phosphate buffer (pH 3.35) and mobile phase B as acetonitrile and water (90:10, v/v). The detector signal was monitored at UV 250 nm. Analytical performance of the optimized UPLC method was validated as per International Conference on Harmonization guidelines. The linearity ranges for OLM, AMB and HCT were 0.59-240, 0.30-60 and 0.37-150 μg/ml, respectively, with correlation coefficients >0.999. The dosage form was subjected to forced-degradation conditions of neutral, acidic and alkaline hydrolysis, oxidation and thermal and photodegradation. The method was proved to be stability indicating by demonstrating the specificity of the drugs from degradation products. The robustness of the method was evaluated through a two-level, three-factorial design with a multivariate approach. Statistical data analysis with best model fit P-value < 0.05 from an ANOVA test indicated that the influence of individual factors is relatively higher than the interaction effects. The method is useful for the analysis of drug products.
Topics: Amlodipine; Chromatography, High Pressure Liquid; Drug Contamination; Drug Stability; Hydrochlorothiazide; Limit of Detection; Linear Models; Olmesartan Medoxomil; Reproducibility of Results; Research Design; Tablets
PubMed: 34110035
DOI: 10.1002/bmc.5194 -
Drug Delivery and Translational Research Mar 2022Hypertension is a common disease for human with high morbidity and mortality, and olmesartan medoxomil (OM) is widely used in the therapy of hypertension. However, poor...
Hypertension is a common disease for human with high morbidity and mortality, and olmesartan medoxomil (OM) is widely used in the therapy of hypertension. However, poor water solubility and low bioavailability limit its widespread use. To improve the effect of OM, a ternary OM solid dispersion consisting of hydroxypropyl-β-cyclodextrin (HP-β-CD) and hydroxypropyl methylcellulose (HPMC) was prepared by mechanochemical method. The best preparation parameters were OM/HP-β-CD/HPMC-E5 with mass ratio of 1:2.6:1 and milling time of 4 h. Under the optimal preparation conditions, the solubility of the ternary solid dispersion could be increased by 12 times as compared with pure OM. Due to the addition of HPMC-E5, the solid dispersion had sustained release performance with prolonged release time of 12 h. Furthermore, in vivo study demonstrated that the prepared solid dispersion could afford significantly improved bioavailability of ~ 3-fold in comparison with pure drug. Hence, the prepared ternary solid dispersion of OM may be a promise delivery system for clinical application.
Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Oral; Biological Availability; Delayed-Action Preparations; Humans; Hypertension; Hypromellose Derivatives; Olmesartan Medoxomil; Particle Size; Solubility; Technology
PubMed: 33860449
DOI: 10.1007/s13346-021-00959-w -
High Blood Pressure & Cardiovascular... May 2021Essential hypertension is the most common cardiovascular (CV) risk factor, being primarily involved in the pathogenesis of CV disease and mortality worldwide. Given the... (Review)
Review
Essential hypertension is the most common cardiovascular (CV) risk factor, being primarily involved in the pathogenesis of CV disease and mortality worldwide. Given the high prevalence and growing incidence of this clinical condition in the general population in both high and low-income countries, antihypertensive drug therapies are frequently prescribed in different hypertension-related CV diseases and comorbidities. Among these conditions, evidence are available demonstrating the clinical benefits of lowering blood pressure (BP) levels, particularly in those hypertensive patients at high or very high CV risk profile. Preliminary studies, performed during the Sars-COVID-19 epidemic, raised some concerns on the potential implication of hypertension and antihypertensive medications in the susceptibility of having severe pneumonia, particularly with regard to the use of drugs inhibiting the renin-angiotensin system (RAS), including angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). These hypotheses were not confirmed by subsequent studies, which independently and systematically demonstrated no clinical harm of these drugs also in patients with Sars-COVID-19 infection. The aim of this narrative review is to critically discuss the available evidence supporting the use of antihypertensive therapies based RAS blocking agents in hypertensive patients with different CV risk profile and with additional clinical conditions or comorbidities, including Sars-COVID-19 infection, with a particular focus on single-pill combination therapies based on olmesartan medoxomil.
Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; COVID-19; Comorbidity; Humans; Hypertension; Olmesartan Medoxomil; Pandemics; Pneumonia, Viral; Renin-Angiotensin System; SARS-CoV-2
PubMed: 33710599
DOI: 10.1007/s40292-021-00443-z -
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 -
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 -
Hypertension Research : Official... Jun 2021Circadian fluctuation disorder of the intrarenal renin-angiotensin system (RAS) causes that of blood pressure (BP) and renal damage. In renal damage with an impaired...
Circadian rhythm of the intrarenal renin-angiotensin system is caused by glomerular filtration of liver-derived angiotensinogen depending on glomerular capillary pressure in adriamycin nephropathy rats.
Circadian fluctuation disorder of the intrarenal renin-angiotensin system (RAS) causes that of blood pressure (BP) and renal damage. In renal damage with an impaired glomerular filtration barrier, liver-derived angiotensinogen (AGT) filtered through damaged glomeruli regulates intrarenal RAS activity. Furthermore, glomerular permeability is more strongly affected by glomerular hypertension than by systemic hypertension. Thus, we aimed to clarify whether the circadian rhythm of intrarenal RAS activity is influenced by AGT filtered through damaged glomeruli due to glomerular capillary pressure. Rats with adriamycin nephropathy and an impaired glomerular filtration barrier were compared with control rats. In adriamycin nephropathy rats, olmesartan medoxomil (an angiotensin II type 1 receptor blocker) or hydralazine (a vasodilator) was administered, and the levels of intrarenal RAS components in the active and rest phases were evaluated. Moreover, the diameter ratio of afferent to efferent arterioles (A/E ratio), an indicator of glomerular capillary pressure, and the glomerular sieving coefficient (GSC) based on multiphoton microscopy in vivo imaging, which reflects glomerular permeability, were determined. Mild renal dysfunction was induced, and the systemic BP increased, resulting in increased A/E ratios in the adriamycin nephropathy rats compared with the control rats. Fluctuations in intrarenal RAS activity occurred in parallel with circadian fluctuations in glomerular capillary pressure, which disappeared with olmesartan treatment and were maintained with hydralazine treatment. Furthermore, the GSCs for AGT also showed similar changes. In conclusion, intrarenal RAS activity is influenced by the filtration of liver-derived AGT from damaged glomeruli due to circadian fluctuation disorder of the glomerular capillary pressure.
Topics: Angiotensinogen; Animals; Circadian Rhythm; Doxorubicin; Glomerular Filtration Rate; Hydralazine; Hypertension; Kidney Diseases; Liver; Rats; Renin-Angiotensin System
PubMed: 33558668
DOI: 10.1038/s41440-021-00620-6 -
Drug Metabolism and Pharmacokinetics Feb 2021In the present study, the biodistribution of self-microemulsifying drug delivery system of hydrophobic olmesartan medoxomil (OM-SMEDDS) was determined by labeling with a...
In the present study, the biodistribution of self-microemulsifying drug delivery system of hydrophobic olmesartan medoxomil (OM-SMEDDS) was determined by labeling with a fluorescent dye VivoTag®680 XL and Xenolight® DiR. Labeled OM-SMEDDS and control dye solution administered orally to mice; real-time dynamic biodistributions over 7 h were determined by 2D-fluorescent imaging to verify their anatomic location. Fluorescent Emissions by Vivotag 680® XL and Xenolight® DiR labeled OM-SMEDDS emitted 2 to 24 times stronger emission than control dye administered group. To further confirm the results, organs were removed and examined using the same technique at the end of 7 h. VivoTag®680XL and Xenolight® DiR emitted 4 and 1.7 times stronger emission respectively than control dye administered mice in ex-vivo organ imaging studies. This study showed that OM-SMEDDS can be succesfully labeled with fluorescent dye and tracked with optical imaging method for the visualisation of biodistribution of drugs and is also useful for enhanced bioavailability.
Topics: Administration, Oral; Animals; Drug Delivery Systems; Emulsifying Agents; Fluorescent Dyes; Male; Mice; Olmesartan Medoxomil; Optical Imaging; Solubility; Tissue Distribution
PubMed: 33191089
DOI: 10.1016/j.dmpk.2020.10.004 -
Drug Development and Industrial Pharmacy Dec 2020The solubility and solution thermodynamic properties of a weakly water-soluble compound olmesartan medoxomil (OLM) in binary 'polyethylene glycol (PEG-400) + water'...
The solubility and solution thermodynamic properties of a weakly water-soluble compound olmesartan medoxomil (OLM) in binary 'polyethylene glycol (PEG-400) + water' cosolvent compositions were determined. The 'mole fraction solubility ( )' of OLM in binary 'PEG-400 + water' cosolvent compositions and pure solvents (PEG-400 and water) was determined at ' = 295.15-330.15 K' and ' = 0.1 MPa'. The Hansen solubility parameter (HSP) of OLM, pure PEG-400, pure water, and binary 'PEG-400 + water' cosolvent compositions free of OLM were also predicted. The obtained values of OLM were correlated using 'van't Hoff, modified Apelblat, Yalkowsky-Roseman, Jouyban-Acree and Jouyban-Acree-van't Hoff' computational models with the error values of <4.0%. The maximum and minimum value of OLM was predicted in neat PEG-400 (1.15 × 10 at = 330.15 K) and neat water (1.90 × 10 at = 295.15 K), respectively. The OLM HSP was predicted to be more close with that of neat PEG-400. The value of OLM was found increased significantly with increase in temperature and PEG-400 mass fraction in all 'PEG-400 + water' cosolvent compositions including neat PEG-400 and neat water. An 'apparent thermodynamic analysis' studies presented an 'endothermic and entropy-driven dissolution' of OLM in all 'PEG-400 + water' cosolvent compositions including pure PEG-400 and pure water.
Topics: Olmesartan Medoxomil; Polyethylene Glycols; Solubility; Solvents; Thermodynamics; Water
PubMed: 33151111
DOI: 10.1080/03639045.2020.1847136 -
Spectrochimica Acta. Part A, Molecular... Feb 2021Versatile, extraction-free univariate spectrophotometric methods have been modified to get effective spectral resolution of mixtures in accordance with their feature...
Versatile, extraction-free univariate spectrophotometric methods have been modified to get effective spectral resolution of mixtures in accordance with their feature challenges. The proposed methods have been applied and validated for analyzing some antihypertensive medicines in their co-formulated medicinal products. Two mixtures have been used: the first one [Mix I ] is composed of Olmesartan medoxomil (OLM) and Amlodipine besylate (ADB) with partly-overlapped spectra while the second [Mix II ] is made up Telmisartan (TEL) and Hydrochlorothiazide (HCT) with total-overlapped spectra. Induced dual wavelength, absorbance correction and ratio subtraction coupled with constant multiplication methods were applied to Mix I , while dual wavelength, advanced absorbance subtraction and constant center coupled with spectrum subtraction methods were applied to Mix II Calibration graphs were established with good correlation coefficients. The methods exhibit significant advantages as simplicity, sensitivity, minimal data manipulation besides optimum robustness. Selectivity was inspected using lab-mixtures with diverse ratios. Accuracy, precision and repeatability were found to be within the acceptable limits. The proposed methods are good enough to be used for co-assay of analytes in combined forms without any interfering from excipients. Moreover, all results were estimated in accordance with ICH criteria and successfully compared with those of the reported methods applying t-test and F-test at 95% confidence level. Generally, these methods can be used efficiently for routine quality control testing.
Topics: Amlodipine; Antihypertensive Agents; Spectrophotometry; Tablets
PubMed: 33126135
DOI: 10.1016/j.saa.2020.119080 -
Journal of Pharmaceutical and... Jan 2021Determination of azide as an impurity in medicinal products was performed for the following sartans with tetrazole functional group (synthesized with the use of azide...
A novel simple and precise method for the determination of azide impurity in sartans using headspace gas chromatography with two dissimilar capillary columns and two flame ionization detectors (HS-GC-FID/FID).
Determination of azide as an impurity in medicinal products was performed for the following sartans with tetrazole functional group (synthesized with the use of azide ion): candesartan, losartan, irbesartan, olmesartan medoxomil, and valsartan. This was achieved using headspace gas chromatography using a dual column/dual flame ionization detector (HS-GC-FID/FID). The method was linear in range, from 5.0-30.0 μg/g, with a coefficient of determination of >0.998 (R). The limit of quantification was 5.0 μg/g and the detection limit was 1.9 μg/g. The sample preparation procedure is fast and simple. The validation procedure was performed in accordance with International Conference on Harmonization (ICH) and Pharmacopeia guidelines. Moreover, besides the content of azide ions, trace quantities of residual solvents (methanol, ethanol, acetone, isopropanol) were found in the majority of sartan tablets.
Topics: Angiotensin II Type 1 Receptor Blockers; Azides; Chromatography, Gas; Flame Ionization; Methanol
PubMed: 33099116
DOI: 10.1016/j.jpba.2020.113671