A Review of Olmesartan-based Therapy in Targeting Effective Blood Pressure Control and Achieving Blood Pressure Goals.

For >3 decades now, angiotensin receptor blockers (ARB) have been used in the management of hypertension (HTN) and HTN-related cardiovascular (CV) diseases. Olmesartan medoxomil (OLM) is an angiotensin II type 1 (AT1) receptor antagonist (or blocker) that binds tightly to the AT1 receptor with long-lasting efficacy over the 24-hour period and safety demonstrated in several trials. It is well tolerated and effective in reducing blood pressure (BP) in mono and combination therapy with thiazide diuretics or calcium channel blockers across a wide range of patient subgroups. The effectiveness and safety of OLM-based combination therapies have good and tolerable profiles with high adherence in the fixed single-pill formulation. Consistent antihypertensive efficacy and good tolerability when used as monotherapy or as a combined therapy make OLM a valuable treatment option for adults with HTN. In this review, we discuss the important clinical implications of OLM as an optimal choice as monotherapy and combination therapy in managing patients with HTN.

An immunochromatographic strip sensor for rapid and sensitive detection of candesartan, olmesartan medoxomil, and irbesartan in herbal beverages.

Sartans, as a class of antihypertensive drugs, pose a threat to human health when illegally added to herbal beverages. It is crucial to detect sartans in herbal beverages. We have developed a highly sensitive monoclonal antibody against candesartan (CAN), olmesartan medoxomil (OLM), and irbesartan (IRB), with 50% inhibitory concentrations (IC50) that were obtained via indirect enzyme-linked immunosorbent assay (ic-ELISA) as 0.178 ng mL-1, 0.185 ng mL-1, and 0.262 ng mL-1 against CAN, OLM, and IRB, respectively. Based on this monoclonal antibody, we developed a rapid screening method for CAN, OLM, and IRB in herbal beverage samples using an immunochromatographic assay (ICA) strip. Test for 15 minutes after simple and rapid sample pre-treatment and the results of this method can be obtained through naked eye observation. The detection limits (LODs) of the ICA strip for CAN, OLM, and IRB in herbal beverage samples are lower than 0.15 ng mL-1, and the results of the ICA strip and ic-ELISA are consistent in spiked samples and recovery experiments. Therefore, this method can quickly, efficiently, and reliably achieve high-throughput on-site rapid detection of illegally added CAN, OLM, and IRB in herbal beverages.

Acute quadruple extremity compartment syndrome due to angio-oedema after polypharmacy overdose including olmesartan medoxomil, telmisartan and vildagliptin.

This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman who consumed an overdose of multiple medications: nifedipine, azelnidipine, amlodipine besylate, olmesartan medoxomil, telmisartan, esaxerenone and vildagliptin. She presented with haemodynamic instability, necessitating intubation. Despite stabilising haemodynamic parameters within 24 hours, she manifested escalating extremity oedema. At 52 hours after ingestion, mottled skin was observed, along with necrotic alterations in the swollen hands and compartment pressures exceeding 30 mm Hg in all extremities. ACS was diagnosed, leading to fasciotomies. The aetiology is postulated to be drug-induced angio-oedema, possibly intensified by the concurrent overdose of olmesartan medoxomil, telmisartan and vildagliptin, each of which has a risk of angio-oedema even at standard dosages. This scenario is a very rare case caused by drug-induced angio-oedema, which underscores the importance of vigilant monitoring to detect ACS in patients with progressing limb oedema.

Efficacy and safety of olmesartan medoxomil-amlodipine besylate tablet in Chinese patients with essential hypertension: A prospective, single-arm, multi-center, real-world study.

There lacks real-world study with a large sample size assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM-AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM-AML (20/5 mg) tablet were analyzed in the current prospective, single-arm, multi-center, real-world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was -10.8 ± 0.4/-6.6 ± 0.3 mmHg at W4 and -12.7 ± 0.5/-7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home-measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients' and physicians' satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug-related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM-AML tablet is one of the best antihypertensive agents in patients with essential hypertension.

Real-World Effectiveness and Safety of a Single-Pill Combination of Olmesartan/Amlodipine/Hydrochlorothiazide in Korean Patients with Hypertension and Cardiovascular Risk Factors.

INTRODUCTION: Patients with hypertension and additional cardiovascular risk factors pose a challenge by requiring more intensive blood pressure (BP) control. Single-pill combination (SPC) therapy can benefit these patients by improving medication adherence. METHODS: This prospective, multicenter observational study assessed the real-world safety and effectiveness of an SPC containing olmesartan, amlodipine, and hydrochlorothiazide (O/A/H) in South Korean patients with hypertension and cardiovascular risk factors. BP control rates, defined as the percentage of patients achieving systolic BP (SBP) < 130 mmHg and diastolic BP (DBP) < 80 mmHg for intensive BP control, and < 140 mmHg and < 90 mmHg, respectively, for standard BP control, were investigated across various cardiovascular risk groups, along with changes in SBP and DBP from baseline to week 24. RESULTS: The most prevalent cardiovascular risk factor was age (≥ 45 years in men, ≥ 55 years in women, 86.1%), followed by cardiovascular diseases (64.4%), dyslipidemia (53.7%), body mass index ≥ 25 kg/m2 (53.5%), and diabetes mellitus (DM) (46.3%). Switching to O/A/H showed significant BP reduction, with a mean change of - 17.8 mmHg/- 9.3 mmHg in SBP/DBP within 4 weeks. The intensive BP control rate was 41.4% (95% confidence interval [CI] 39.5, 43.4), and the standard BP control rate was 73.3% (95% CI 71.5, 75.1), with better control rates in the risk age group (43.1% and 74.1%, respectively) and cardiovascular disease group (42.0% and 73.8%, respectively). The DM group had relatively lower control rates (37.5% for intensive control and 69.4% for standard control). Common adverse drug reactions included dizziness (2.91%), hypotension (1.51%), and headaches (0.70%). CONCLUSION: The SPC therapy of O/A/H caused a rapid and sustained reduction in SBP/DBP in patients' hypertension and additional cardiovascular risk factors. The therapy was safe and well tolerated. STUDY REGISTRATION NUMBER: KCT0003401 ( https://cris.nih.go.kr/cris/search/detailSearch.do/20795 ).

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.

A novel nano-formulation of olmesartan medoxomil with improved delivery and efficacy in the treatment of indomethacin-induced duodenitis in rats.

There are few studies addressing duodenal inflammation. This study was designed to investigate the effects of a recently developed biotechnological product, a nano-formulation of olmesartan medoxomil (OM) - olmesartan medoxomil zeinmersomes (OMZ) - for the treatment of indomethacin-induced duodenitis in rats. Adult male Wistar rats were given indomethacin (10 mg/kg/day) for four weeks. They were divided into a positive control group (PC, untreated) and two groups treated orally with 3 mg/kg per day of OM or OMZ for the last two weeks of the 4-week indomethacin-treatment. At end of the four weeks, blood and duodenum were collected. Duodenal homogenate was used for measurement of levels of myeloperoxidase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde, reduced glutathione (GSH), and cleaved caspase-3. Duodenal sections were stained with H&E. Gene expressions of nuclear factor kappa B (NF-κB p65), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) by RT-PCR, and protein expression of survivin by western blot were assessed. Plasma and duodenal olmesartan concentrations were measured by high performance liquid chromatography mass spectrometry. The duodenitis rats showed significantly higher duodenal levels of myeloperoxidase, TNF-α, IL-6, malondialdehyde, and cleaved caspase-3, a significantly lower GSH level, and histopathological alterations. Moreover, they showed upregulated gene expressions of NF-κB p65 and Bax, downregulated gene expression of Bcl-2, decreased Bcl-2/Bax ratio, and lower protein expression of survivin. OMZ was more effective in protecting the duodenum from indomethacin-induced injuries compared to OM due to improved delivery, higher bioavailability, and better anti-inflammatory, antioxidant, and antiapoptotic effects. OMZ could be a better choice for hypertensive patients with non-steroidal anti-inflammatory drugs-induced duodenitis.

Coupling of synchronous fluorescence spectroscopy with derivative amplitude outcomes for simultaneous determination of metoprolol succinate and olmesartan medoxomil in combined pharmaceutical preparation: Application in spiked human plasma.

For the first time a spectrofluorimetric method had been achieved for the concurrent analysis of metoprolol succinate (MET) and olmesartan medoxomil (OLM). The approach depended on assessing the first order derivative (1D) of the synchronous fluorescence intensity of the two drugs in aqueous solution at Δλ of 100 nm. The amplitudes of 1D at 300 nm and 347 nm were measured for MET and OLM, respectively. The linearity ranges were 100-1000 ng/mL and 100-5000 ng/mL for OLM and MET, respectively. This approach is uncomplicated, repetitive, quick, and affordable. The results of analysis had been statistically verified. The validation assessments were carried out following the recommendations of The International Council for Harmonization (ICH). This technique could be employed to assess marketed formulation. The method was sensitive with limits of detection (LOD) of 32 ng/ml and 14 ng/mL for MET and OLM, respectively. Limits of quantitation (LOQ) were 99 ng/ml for MET and 44 ng/mL for OLM. So it can be applied to determine both drugs in spiked human plasma within the linearity ranges of 100-1000 ng/mL for OLM and 100-1500 ng/mL for MET.

Single-Pill Combination with Three Antihypertensive Agents to Improve Blood Pressure Control in Hypertension: Focus on Olmesartan-Based Combinations.

Blood pressure control remains an unmet clinical need. Only about half of patients achieve their blood pressure (BP) targets and of these, the majority require combination and double or triple therapies. International guidelines recommend the association of drugs with complementary mechanisms of action and, in particular, the combination of renin-angiotensin system (RAS) inhibitors, calcium channel blockers (CCBs), and diuretics. Among the various angiotensin receptor blockers, olmesartan (OM) is available as a monotherapy and in dual and triple single-pill combinations (SPCs) with amlodipine (AML) and/or hydrochlorothiazide (HCTZ). Several phase III and IV studies, together with real-world studies, have demonstrated the additional benefits of combining OM either with AML or with HCTZ in terms of BP control and target BP achievements both in the general population and in special subgroups of hypertensive patients, such as the elderly, diabetic, chronic kidney disease or obese patients. Ambulatory BP monitoring studies assessing 24h BP have also demonstrated that dual, as well as triple, OM-based SPCs induce a more sustained and smoother BP reduction than placebo and monotherapy. Furthermore, triple OM-based SPC has been shown to improve therapeutic adherence in hypertensive patients compared to free combinations. The availability of OM combined with HCTZ, AML or both at different dosages makes it a valuable option to customize therapy based on the levels of BP and the clinical characteristics of hypertensive patients.

Chitosan nanoparticles for intranasal delivery of olmesartan medoxomil: Pharmacokinetic and pharmacodynamic perspectives.

Nasal drug delivery has the potential to improve the systemic bioavailability of drugs with low oral bioavailability. Olmesartan medoxomil (OLM) is one of the most popular drugs for the treatment of hypertension with poor oral bioavailability of approximately 26 %. In this context, the goal of this work was to synthesize chitosan nanoparticles (CS NPs) loaded with OLM using the ionotropic gelation method to enhance the bioavailability and decrease oral side effects through nasal route. The particle size (PS), zeta potential (ZP), entrapment efficiency (%EE), and ex-vivo transmucosal permeation study of CS NPs were all evaluated. The pharmacokinetic and pharmacodynamic studies of selected formula compared to oral and nasal OLM suspensions were conducted. Successful formation of spherically shaped OLM CS NPS in the nano-range (240.02-344.45 nm) favorable for the intranasal absorption with high %EE (75.2-83.51 %) was achieved. The ability of OLM CS NPs to permeate efficiently across the nasal mucosa was proven in an ex vivo permeation experiment. Pharmacokinetic study demonstrated that the intranasal administration of OLM CS NPs exhibited improved bioavailability by 11.3-folds relative to oral OLM suspension as indicated by higher AUC value. The superior effect of intranasal OLM CS NPs was also accentuated in l-NAME induced hypertensive rats compared to intranasal and oral OLM suspension by reducing the high blood pressure (BP) and improving the heart rate (HR) of the induced group. Histological examinations revealed no damage occurred to nasal mucosa. In conclusion, OLM CS NPs had the ability to significantly improve the bioavailability of OLM and decrease BP and HR, suggesting the potential application of CS NPs as a promising carrier for the systemic delivery of OLM via intranasal route.

Development of a Sensitive Screening Method for Simultaneous Determination of Nine Genotoxic Nitrosamines in Active Pharmaceutical Ingredients by GC-MS.

A worldwide crisis with nitrosamine contamination in medical products began in 2018. Therefore, trace-level analysis of nitrosamines is becoming an emerging topic of interest in the field of quality control. A novel GC-MS method with electron ionization and microextraction was developed and validated for simultaneous determination of nine carcinogenic nitrosamines (NDMA, NMEA, NDEA, NDBA, NMOR, NPYR, NPIP, NDPA, and N-methyl-npz) in active pharmaceutical ingredients (APIs): cilostazol, sunitinib malate, and olmesartan medoxomil. The method was validated according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, demonstrating good linearity in the range of LOQ up to 21.6 ng/mL (120% of specification limit). The limits of detection for the nine nitrosamines were determined to be in the range 0.15-1.00 ng/mL. The developed trace level GC-MS method turned out to be specific, accurate, and precise. The accuracy of all the tested APIs ranged from 94.09% to 111.22% and the precision evaluated by repeatability, intermediate precision, and system precision was RSD ≤ 7.65%. Nitrosamines were not detected in cilostazol and sunitinib, whereas in olmesartan medoxomil NDEA was detected at the level of LOQ. The novel protocol was successfully applied for nitrosamines determination in selected APIs and can be used for the routine quality control of APIs under Good Manufacturing Practices rules, ensuring the safety and effectiveness of pharmaceutical products.

Permeability of olmesartan medoxomil from lipid based and suspension formulations using an optimized HDM-PAMPA model.

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. In vivo 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% v/w 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 (Pe) 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.

Olmesartan Ameliorates Organ Injury and Mortality in Rats With Peritonitis-Induced Sepsis.

INTRODUCTION: Sepsis and related complications lead to high morbidity and mortality in humans and animals. Olmesartan medoxomil (OLM), a nonpeptide angiotensin II type 1 receptor blocker, has antiinflammatory and antioxidative effects in various experimental animal models. The present study aimed to investigate whether OLM protects against sepsis in a clinically relevant model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). METHODS: Sepsis was induced by CLP in anesthetized rats. OLM was administered intraperitoneally 3 h after CLP onset. Hemodynamic, biochemical, and inflammatory parameters were analyzed. RESULTS: The administration of OLM in CLP rats significantly improved their survival rate. Moreover, OLM mitigated CLP-induced hypotension and organ injury (indicated by biochemical parameters), but not tachycardia. OLM significantly reduced the plasma levels of interleukin-6 and nitric oxide. CONCLUSIONS: OLM markedly attenuated CLP-induced hypotension and organ injury, and hence improved survival by inhibiting the inflammatory response and nitrosative stress in this clinically relevant model of sepsis.

Olmesartan medoxomil self-microemulsifying drug delivery system reverses apoptosis and improves cell adhesion in trinitrobenzene sulfonic acid-induced colitis in rats.

Olmesartan medoxomil (OM) is an angiotensin receptor blocker. This study aimed to investigate the effects of OM self-microemulsifying drug delivery system (OMS) in trinitrobenzene sulfonic acid (TNBS)-induced acute colitis in rats. Besides two control groups, five TNBS-colitic-treated groups (n = 8) were given orally sulfasalazine (100 mg/kg/day), low and high doses of OM (3.0 and 10.0 mg/kg/day) (OML and OMH) and of OMS (OMSL and OMSH) for seven days. A colitis activity score was calculated. The colon was examined macroscopically. Colonic levels of myeloperoxidase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde, and reduced glutathione were measured. Plasma and colonic olmesartan levels were measured. Colonic sections were subjected to hematoxylin and eosin staining and immunohistochemical staining for E-cadherin, caspase-3, and matrix metalloproteinase-9 (MMP-9). Protein expression of E-cadherin, Bcl-2 associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2), and cleaved caspase-3 by Western blot was done. TNBS-colitic rats showed increased colonic myeloperoxidase, TNF-α, IL-6, and malondialdehyde, decreased colonic glutathione, histopathological, immunohistochemical, and protein expression alterations. OMS, compared with OM, dose-dependently achieved higher colonic free olmesartan concentration, showed better anti-inflammatory, antioxidant, and anti-apoptotic effects, improved intestinal barrier, and decreased mucolytic activity. OMS more effectively up-regulated the reduced Bcl-2, Bcl-2/Bax ratio, and E-cadherin expression, and down-regulated the overexpressed Bax, cleaved caspase-3, and MMP-9. OMSL exerted effects comparable to OMH. Sulfasalazine exerted maximal colonic protective effects and almost completely reversed colonic damage, and OMSH showed nearly similar effects with non-significant differences in-between or compared with the normal control group. In conclusion, OMS could be a potential additive treatment for Crohn's disease colitis.

Effects of α lipoic acid combined with olmesartan medoxomil on blood glucose and oxidation indicators in patients with diabetic nephropathy: A protocol for a parallel, randomized, double-blind, controlled clinical trial.

BACKGROUND: Diabetic nephropathy (DN) is a common microvascular complication of diabetes, which poses a serious threat to the health and life of patients. There is evidence that both α lipoic acid and olmesartan medoxomil have positive effects in the treatment of DN, but whether the 2 have synergistic effects and the effects on blood glucose and oxidation indicators are controversial. METHODS: This is a prospective parallel, randomized, double-blind, placebo-controlled trial to study the effects of α lipoic acid in combination with olmesartan medoxomil on blood glucose and oxidation indicators in patients with DN. Participants will be randomly assigned to a treatment group, which will receive α lipoic acid dispersive tablets combined with olmesartan medoxomil tablets, or a control group, which will receive olmesartan medoxomil tablets combined with placebo for 4 weeks, followed up for 12 weeks. Observation indicators include: glycemic indicators [fasting blood glucose, 2 hours postprandial blood glucose and glycosylated hemoglobin], the oxidation indicators [serum glutathione, superoxide dismutase, malondialdehyde, 8-hydroxydeox-yguanosine], and adverse reactions. Finally, SPASS 22.0 software will be used for statistical analysis of the data. DISCUSSION: This study will evaluate the effects of α lipoic acid combined with olmesartan medoxomil on blood glucose and oxidation indicators in patients with DN. The results of this study will provide a reference for the clinical use of α lipoic acid combined with olmesartan medoxomil in the treatment of DN. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/VJWXS.

Pharmacokinetics and Bioequivalence Evaluation of 2 Olmesartan Medoxomil and Amlodipine Besylate Fixed-Dose Combination Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

Combined antihypertensive drugs have become the basic method of treating hypertension. Olmesartan and amlodipine, as representative drugs of angiotensin receptor blockers and calcium channel blockers, were developed as a compound formulation for antihypertensive treatment. The purpose of this study was to evaluate the bioequivalence of olmesartan medoxomil/amlodipine besylate tablet (20 mg/5 mg) under fasting and fed conditions in healthy Chinese volunteers. A phase 1 randomized, open-label, 2-period, single-dose crossover study (n = 56) was designed, with subjects under fasting (n = 28) or fed (n = 28) conditions. Of the 56 enrolled participants, 55 healthy volunteers completed the study. Blood samples for pharmacokinetic analysis were collected from 1.5 hours before dosing to 168 hours after dosing. The 90%CIs for the geometric mean ratios of maximum plasma drug concentration, area under the plasma concentration-time curve (AUC) from time 0 to the last measurable concentration and AUC from time 0 to infinity of the test/reference were all within the acceptance range for bioequivalence (80%-125%). The data showed that the absorption of amlodipine is not affected by food, but the exposure of olmesartan (both AUC from time 0 to the last measurable concentration and AUC from time 0 to infinity were P < .05) reduced significantly after consuming a high-fat meal, which indicates that the effects of food on olmesartan exposure in healthy Chinese were clinically relevant. During the study, there were no suspected serious adverse reactions or serious adverse events. All adverse events were determined to be mild after Common Terminology Criteria for Adverse Events 5.0 evaluation. These results indicated that both the test and reference formulations were bioequivalent with similar safety profiles.

"Ghost peaks" of olmesartan medoxomil: Two solution degradation products of olmesartan medoxomil via oxidation mediated by metal ions.

Two unknown solution degradants were found during the dissolution testing in 0.1-M HCl for olmesartan medoxomil (OLM) tablets. The structure of the degradants was identified and characterized by liquid chromatography-ultraviolet (LC-UV), liquid chromatography with tandem mass spectrometry (LC-MS/MS), and nuclear magnetic resonance (NMR) and demonstrated to be cyclization of tetrazole and benzene in the olmesartan (OL) and OLM structures. A series of studies including stress studies, simulation studies, and mechanism-based studies were performed to reveal the potential mechanisms that lead to the formation of the unknown degradants. The study results demonstrated that the degradation was catalyzed with radicals that originated from the metal ions leached from the inner surface of high-performance liquid chromatography (HPLC) glass vials with dissolved oxygen under acidic condition. Prerinsing the glass vials with acidic solution dissolved with EDTA can effectively avoid the generation of such oxidative impurities. The present work provides new insights into the understanding of degradation pathways of OLM, which might support the development of OLM tablets.

Four chemometric spectrophotometric methods for simultaneous estimation of amlodipine besylate and olmesartan medoxomil in their combined dosage form.

For determination of amlodipine besylate (AML) and olmesartan medoxomil (OLM) at the same time, four UV chemometric spectrophotometric techniques were created and tested in accordance with ICH standards. Method (I) was absorption subtraction method (ASM) using two wavelengths, one of which was of AML at 365 nm and the other was the isoabsorptive point of both drugs at 237 nm. Method (II) was ratio subtraction method (RSM) for determination of OLM at λmax = 254 nm by taking the ratio spectrum and subtracting the constant values using 10 µg/mL of AML as a divisor in combination with extended ratio subtraction method (ERSM) to determine AML at λmax = 239 nm using 10 µg/mL OLM as a divisor. Method (III) was dual wavelength method; the wavelengths used to determine OLM were 221 nm and 235 nm, while those used to determine AML were 246 nm and 259 nm. Method (IV) was the second order derivative (2D) spectrophotometric method at 219 nm for OLM and 227 nm for AML. The proposed approaches were used to achieve linearity in the concentration range of 2-25 µg/mL for both drugs. The approaches were found to be uncomplicated, reproducible, efficient, and cost-effective as well as they were successfully used to determine the cited drugs in both laboratory samples and commercial pharmaceutical formulations.

Preparation of olmesartan medoxomil solid dispersion with sustained release performance by mechanochemical technology.

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-ß-cyclodextrin (HP-ß-CD) and hydroxypropyl methylcellulose (HPMC) was prepared by mechanochemical method. The best preparation parameters were OM/HP-ß-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.

Validated Spectrophotometric Methods for Simultaneous Determination of Atorvastatin Calcium and Olmesartan Medoxomil in Their Pharmaceutical Formulation.

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.