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Pharmaceutics Feb 2022A drug-drug and drug-excipient interactions and compatibilities study was conducted for two fixed-dose combination (FDC) products containing olmesartan medoxomil...
A drug-drug and drug-excipient interactions and compatibilities study was conducted for two fixed-dose combination (FDC) products containing olmesartan medoxomil (OLM)/hydrochlorothiazide (HCT) 20/12.5 mg and OLM/HCT 40/12.5 mg during their development including storage. The study consisted of the evaluation of samples retrieved during all stages of a real manufacturing process. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transform infrared spectroscopy (FT-IR), and contact angle techniques were applied to the samples to determine interactions and incompatibilities. Dissolution tests and long-term stability studies were conducted to evaluate dosage form performance. Results showed weak solid-state interactions able to obtain a eutectic mixture of OLM and HCT while microcrystalline cellulose (MC) impacted the thermal stability of both drugs. Reliable dissolution and long-term stability tests confirmed that the interactions observed were not considered incompatibilities because they were not influenced by the performance of the final products.
PubMed: 35214156
DOI: 10.3390/pharmaceutics14020424 -
The Journal of Pharmacy Technology :... Feb 2022Olmesartan medoxomil (OLM) is only available in the United States as tablets. The United States Pharmacopoeia (USP) has placed OLM on its priority list of preparations...
Olmesartan medoxomil (OLM) is only available in the United States as tablets. The United States Pharmacopoeia (USP) has placed OLM on its priority list of preparations that require stability data to support practitioner compounding. The purpose of the study was to develop a stability-indicating assay and then determine the beyond-use date (BUD) for an extemporaneous OLM suspension. A reverse-phase high-performance liquid chromatography (HPLC) assay was developed and validated according to guidelines for USP official compounded monographs. OLM 2 mg/mL suspensions were compounded with Ora-Sweet and Ora-Plus and stored at room temperature or in a refrigerator. Suspensions were assayed periodically over 90 days for OLM concentration and observed for physical stability. The pH was measured at the beginning and end of the study. The OLM concentration remained above 97% of the starting concentration for 90 days when stored in the refrigerator and above 94% of the starting concentration for 90 days when stored at room temperature. The suspension pH did not change and indicators of physical stability were unchanged for 90 days. OLM 2 mg/mL suspensions were chemically and physically stable at room temperature and in the refrigerator for 90 days. The BUD may be set at 90 days under either storage condition.
PubMed: 35141721
DOI: 10.1177/87551225211051756 -
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 -
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 -
Spectrochimica Acta. Part A, Molecular... Feb 2022For determination of amlodipine besylate (AML) and olmesartan medoxomil (OLM) at the same time, four UV chemometric spectrophotometric techniques were created and tested...
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 λ = 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 λ = 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 (D) 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.
Topics: Amlodipine; Olmesartan Medoxomil; Spectrophotometry; Tablets
PubMed: 34624815
DOI: 10.1016/j.saa.2021.120455 -
Polymers Jul 2021Olmesartan medoxomil (OLM) is one of the prominent antihypertensive drug that suffers from low aqueous solubility and dissolution rate leading to its low...
Olmesartan medoxomil (OLM) is one of the prominent antihypertensive drug that suffers from low aqueous solubility and dissolution rate leading to its low bioavailability. To improve the oral bioavailability of OLM, a delivery system based on ethylcellulose (EC, a biobased polymer) nanosponges (NSs) was developed and evaluated for cytotoxicity against the A549 lung cell lines and antihypertensive potential in a rat model. Four OLM-loaded NSs (ONS1-ONS4) were prepared and fully evaluated in terms of physicochemical properties. Among these formulations, ONS4 was regarded as the optimized formulation with particle size (487 nm), PDI (0.386), zeta potential (ζP = -18.1 mV), entrapment efficiency (EE = 91.2%) and drug loading (DL = 0.88%). In addition, a nanosized porous morphology was detected for this optimized system with NS surface area of about 63.512 m/g, pore volume and pore radius Dv(r) of 0.149 cc/g and 15.274 Å, respectively, measured by nitrogen adsorption/desorption analysis. The observed morphology plus sustained release rate of OLM caused that the optimized formulation showed higher cytotoxicity against A549 lung cell lines in comparison to the pure OLM. Finally, this system (ONS4) reduced the systolic blood pressure (SBP) significantly ( < 0.01) as compared to control and pure OLM drug in spontaneously hypertensive rats. Overall, this study provides a scientific basis for future studies on the encapsulation efficiency of NSs as promising drug carriers for overcoming pharmacokinetic limitations.
PubMed: 34301030
DOI: 10.3390/polym13142272 -
Current Drug Delivery 2021Olmesartan Medoxomil (OM) is an angiotensin receptor blocker and has the adverse effect of celiac like enteropathy which was accepted by the FDA in 2013. This disease is...
INTRODUCTION
Olmesartan Medoxomil (OM) is an angiotensin receptor blocker and has the adverse effect of celiac like enteropathy which was accepted by the FDA in 2013. This disease is characterized by severe diarrhea, weight loss and enteropathy. Although there are many case reports associated with olmesartan-related enteropathy in humans, it has not been described in a long-term animal model study so far.
AIM
We developed a self-microemulsifying drug delivery system (OM-SMEDDS) in our previous study to reduce this side effect of the drug and to enhance bioavailability.
METHODS
In this study, an artificial hypertension model was established with a dose of 185 μmol /kg L-NAME (N ω-nitro-L-arginine methyl ester) twice in a day intraperitoneally in Wistar albino rats. To determine and compare side effects, the OM-Suspension and OM-SMEDDS were administered at 1.3 mg/kg therapeutic dose during one-month period to the rats.
RESULTS
Tension of rats was recorded by measuring from their tails with non invasive blood pressure system. We observed celiac like enteropathy findings like villous atrophy and intraepithelial lymphocytosis and clinical changes like weight loss and severe diarrhea after the treatment with OM-Suspension during one-month experiment. It was also observed that the antihypertensive efficacy of the OM-SMEDDS formulation was higher than the suspension during the experiment, which did not cause enteropathy, diarrhea and weight loss by reducing intestinal exposure.
CONCLUSION
Hereby, we evaluated the side effects of two different pharmaceutical forms by designing a sustainable and reproducible celiac rat model that can be induced with olmesartan medoxomil.
Topics: Animals; Antihypertensive Agents; Imidazoles; Olmesartan Medoxomil; Rats; Rats, Wistar; Tetrazoles
PubMed: 34225629
DOI: 10.2174/1567201818666210322144631 -
Digestive and Liver Disease : Official... Nov 2021
Topics: Angiotensin II Type 1 Receptor Blockers; Collagenous Sprue; Endoscopy, Digestive System; Female; Humans; Olmesartan Medoxomil
PubMed: 34219045
DOI: 10.1016/j.dld.2021.06.010 -
The Journal of Antimicrobial... Aug 2021The SmeVWX efflux pump of Stenotrophomonas maltophilia contributes to menadione (MD) tolerance and resistance to chloramphenicol, quinolones and tetracycline. The...
BACKGROUND
The SmeVWX efflux pump of Stenotrophomonas maltophilia contributes to menadione (MD) tolerance and resistance to chloramphenicol, quinolones and tetracycline. The components of the SmeVWX efflux pump are encoded by a five-gene operon, smeU1VWU2X. We have previously demonstrated that the smeU1VWU2X operon is intrinsically unexpressed and inducibly expressed by MD via a SoxR- and SmeRv-involved regulatory circuit in S. maltophilia KJ. We also inferred that there should be other regulator(s) involved in MD-mediated smeU1VWU2X expression in addition to SoxR and SmeRv.
OBJECTIVES
To identify novel regulator(s) involved in the regulation of MD-mediated smeU1VWU2X expression and elucidate the regulatory circuit.
METHODS
A possible regulator candidate involved in the regulation of MD-mediated smeU1VWU2X expression was identified by a homologue search using the helix-turn-helix domain of SmeRv as a query. Gene expression was assessed using the promoter-xylE transcriptional fusion assay and quantitative RT-PCR. The impact of the regulator on SmeVWX pump-mediated functions was investigated via mutant construction and functional tests (antibiotic susceptibility and MD tolerance).
RESULTS
AzoR (Smlt3089), a LysR-type transcriptional regulator, was investigated. In unstressed logarithmically grown cells, AzoR was abundantly expressed and functioned as a repressor, inhibiting the expression of the smeU1VWU2X operon. MD challenge attenuated azoR expression, thus derepressing the expression of the smeU1VWU2X operon in S. maltophilia KJ. AzoR down-regulation-mediated smeU1VWU2X expression was observed in quinolone-resistant and SmeVWX-overexpressing S. maltophilia clinical isolates.
CONCLUSIONS
AzoR negatively regulates the expression of the smeU1VWU2X operon and SmeVWX pump-mediated antibiotic resistance in S. maltophilia.
Topics: Amlodipine Besylate, Olmesartan Medoxomil Drug Combination; Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Multiple, Bacterial; Membrane Transport Proteins; Microbial Sensitivity Tests; Stenotrophomonas maltophilia
PubMed: 34151959
DOI: 10.1093/jac/dkab203 -
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