Losartan Tablets Research Articles

Water as a green solvent for sustainable sample preparation: single drop microextraction of N-nitrosamines from losartan tablets.

Water, renowned for its sustainability and minimal toxicity, is an ideal candidate for environmentally friendly solvent-based microextraction. However, its potential as an extractant solvent in miniaturized sample preparation remains largely unexplored. This paper pioneers using water as the extraction solvent in headspace single-drop microextraction (HS-SDME) for N-nitrosamines from losartan tablets. Autonomous HS-SDME is executed by an Arduino-controlled, lab-made Cartesian robot, using water for the online preconcentration of enriched extracts through direct injection into a column-switching system. Critical experimental parameters influencing HS-SDME performance are systematically explored through univariate and multivariate experiments. While most previously reported methods for determining N-nitrosamines in pharmaceutical formulations rely on highly selective mass spectrometry detection techniques to handle the strong matrix effects typical of pharmaceutical samples, the water-based HS-SDME method efficiently eliminates the interfering effects of a large amount of the pharmaceutical active ingredient and tablet excipients, allowing straightforward analysis using high-performance liquid chromatography with ultraviolet detection (HPLC-UV-Vis). Under optimized conditions, the developed method exhibits linear responses from 100 to 2400ngg-1, demonstrating appropriate detectability, precision, and accuracy for the proposed application. Additionally, the environmental sustainability of the method is assessed using the AGREEprep methodology, positioning it as an outstanding green alternative for determining hazardous contaminants in pharmaceutical products.

Targeted and untargeted screening for impurities in losartan tablets marketed in Germany by means of liquid chromatography/high resolution mass spectrometry

Technical advances in the field of quality analysis allow an increasingly deeper look into the impurity profile of drugs. The ability to detect unexpected impurities in addition to known impurities ensures the supply of high-quality drugs and can prevent recalls due to the detection of harmful unexpected impurities, as has happened recently with the N-nitrosamine and azido impurities in losartan (LOS) drug products. In the present study, the LC-MS/HRMS approach described by Backer et al. was applied to an even more complex system, being the investigation of 35 LOS drug products and combination preparations purchased in 2018 and 2022 in German pharmacies. The film-coated tablets were analysed by means of four LC-MS/HRMS method variants. For the separation a Zorbax RR StableBond C18 column (3.0 ×100 mm, particle size of 3.5 µm, pore size of 80 Å), a gradient elution and for mass spectrometric detection a qTOF mass spectrometer with electrospray ionization in positive and negative mode was used. An information-dependent acquisition method was applied for the acquisition of high-resolution mass spectrometry data. The combination of an untargeted and a targeted screening approach revealed the finding of eight impurities in total. Beside the five LOS related compounds, LOS impurity F, J, K, L, M, and related compound D from amlodipine besilate, LOS azide and an unknown derivative thereof were detected. Identification and structure elucidation, respectively, were successfully performed using in silico fragmentation. Differences in the impurity profiles of drug products from 2018 and 2022 could be observed. This study shows that broad screening approaches like this are applicable to the analysis of drug products and can be an important enhancement of the quality assurance of medicinal products.

Determining the Influence of Breadfruit Mucilage on the Disintegration and Dissolution of Losartan Fast-Dissolving Tablets

organoleptic characteristics, hydration, swelling capacity, and pasting temperature of breadfruit starch were determined. It was found that breadfruit starch exhibited partial solubility in warm water, a pH of 5.8, and good hydration and swelling capacities. Furthermore, a compatibility test using differential scanning calorimetry confirmed the compatibility of losartan and breadfruit starch. It was determined that the formulated losartan tablets were satisfactory in terms of flow properties as well as consistent drug content both before and after compression. Dissolution studies in-vitro showed improved drug release profiles than those of losartan tablets marketed on the market. According to stability studies, the physical appearance and color of the drug did not change over 3 months, but there was a slight decrease in the amount of the drug and the rate of drug release during that period. Overall, breadfruit starch showed promise as an excipient for losartan tablets, offering potential benefits in terms of enhanced drug release characteristics. Further investigations are necessary to optimize the formulation and evaluate its clinical efficacy and safety.

Microextraction by packed sorbent of N-nitrosamines from Losartan tablets using a high-throughput robot platform followed by liquid chromatography-tandem mass spectrometry.

The development of a fast, cost-effective, and efficient microextraction by packed sorbent setup was achieved by combining affordable laboratory-repackable devices of microextraction with a high-throughput cartesian robot. This setup was evaluated for the development of an analytical method to determine N-nitrosamines in losartan tablets. N-nitrosamines pose a significant concern in the pharmaceutical market due to their carcinogenic risk, necessitating their control and quantification in pharmaceutical products. The parameters influencing the performance of this sample preparation for N-nitrosamines were investigated through both univariate and multivariate experiments. Microextractions were performed using just 5.0mg of carboxylic acid-modified polystyrene divinylbenzene copolymer as the extraction phase. Under the optimized conditions, the automated setup enabled the simultaneous treatment of six samples in less than 20 min, providing reliable analytical confidence for the proposed application. The analytical performance of the automated high-throughput microextraction by the packed sorbent method was evaluated using a matrix-matching calibration. Quantification was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry with chemical ionization at atmospheric pressure. The method exhibited limits of detection as low as 50ng/g, good linearity, and satisfactory intra-day (1.38-18.76) and inter-day (2.66-20.08) precision. Additionally, the method showed accuracy ranging from 80% to 136% for these impurities in pharmaceutical formulations.

Randomized two way crossover open label study to compare the bioequivalence of LOSARDIL 100 TM (Drug International Ltd, Bangladesh) and COZAAR TM (Merck Sharp & Dhome Ltd, UK) in Bangladeshi normal male volunteers

Objectives: A crossover-randomized bioequivalence study of two oral formulations of losartan (100 mg) tablets was carried out in 16 healthy male Bangladeshi volunteers. The test and reference formulations were LOSARDIL 100™ (Drug International Ltd, Bangladesh) and COZAAR™ (Merck Sharp & Dohme Ltd, UK), respectively.
 Methods: Each tablet was administered with 150 mL of water to subjects after whole night fasting condition on two therapy days distinct by 1 week washout period. After administration, blood samples were accumulated periodically for 24 hours. The plasma concentrations of losartan were evaluated using a validated HPLC method. The pharmacokinetic parameters Cmax, Tmax, AUC0→24h, t1/2, and Kel were determined.
 Results: The mean (± SD) AUC0→24h for losartan of test drug LOSARDIL 100TM for 16 volunteers was 3310 ± 1165 ng.hr/mL whereas it was 3545 ± 1251 ng.hr/mL for losartan of COZAARTM . The relative bioavailability (LOSARDIL 100TM/COZAARTM ratio) was 93%. The Cmax, tmax, half-life of elimination (t1/2) and the rate of elimination (Kel) of losartan of test drug were 1855 ± 675 ng/mL, 0.77 ± 0.39 hours, 4.69 ± 1.17 hour and 0.15 ± 0.04 respectively. The Cmax, tmax, half-life of elimination (t1/2) and the rate of elimination (Kel) of losartan of reference drug were 2254 ± 944 ng/mL, 0.87 ± 0.29 hours, 4.13 ± 1.41 hour and 0.20 ± 0.04 respectively. 
 Conclusion: Depend on the statistical interpretation the 90% CI for the test and reference drugs were observed within the acceptance range of 80-125%. In conjecture, LOSARDIL 100™ is bioequivalent to COZAAR ™ in terms of absorption.

Thymol-Based Hydrophobic Deep Eutectic Solvents as a Green Approach for Screening Polar Nitrosamines in Sartans Pharmaceutical Products by Ultrasound-Assisted Dispersive Liquid-Liquid Microextraction Combined with HPLC-DAD

Nitrosamines are carcinogens substances firstly detected in sartans drugs in 2018, leading to new regulations and monitoring programmes that raised the costs and challenges to the pharmaceutical industry. Therefore, reliable and cost-effective methods for screening nitrosamines in medicines are highly desirable. Hydrophobic deep eutectic solvents (HDES), a novel “eco-friendly” alternative to solvents commonly used in microextraction techniques, can meet these requirements. In this study, a simple and rapid method of ultrasound-assisted dispersive liquid-liquid microextraction using thymol-based HDES followed by HPLC-DAD detection was developed for the determination of n-nitrosodimethylamine (NDMA) and n-nitroso-n-methylamino butyric acid (NMBA) from candesartan, irbesartan, losartan, olmesartan, telmisartan and valsartan drug substances, and from losartan tablets. Various influencing factors (such as HDES type, HDES:sample ratio, salt addition and sample pH) were investigated. Best extraction efficiencies were achieved with thymol:benzyl alcohol HDES. Under optimal conditions, the linearities ranged from 15 to 1000 ng mL−1 for both NDMA and NMBA (R² > 0.99), with recoveries between 81.8–104.2% and precision from 0.2 to 14.6%. The limits of detection were 17.3 – 220.0 ng g−1 and 16.3 – 290.0 ng g−1 for NDMA and NMBA, consecutively. Finally, the proposed method was successfully applied in spiked sartans drug substances and in losartan potassium tablets collected in the market.

More US recalls of Torrent Pharmaceuticals' losartan tablets

More US recalls of Torrent Pharmaceuticals' losartan tablets

The Effectivity of Losartan Tablet for Decreasing Fibrotic Tissue Formation in Gastrocnemius Muscle Injury Grade I of Rabbits

Muscle injuries among athletes require a complete recovery to be able to function optimally as before. However, in spite of implementing the management with PRICE (Protection, Rest, Immobilization, Compression and Elevation), during the recovery processes, fibrotic tissue will be formed, which is an unwanted non-functional muscle. Losartan is a blood pressure-lowering drug which has the inhibitory effect of inhibitory effect of TGF-? cytokines (fibrotic tissue regulators). TGF-? is the key to fibrotic formation and differentiation. Losartan has an effect on decreasing the TGF-? production and it may affect the fibrotic tissue. This research is conducted by an experimental comparative method on the rabbit as study objects. Based on Federer formula sampling, twenty samples totally occurred. The random sampling method is adopted for comparing fibrotic tissue in two different groups (control group and losartan group). Losartan is administered orally. There were significant differences in the proportion of fibrotic tissue between the sample groups. The losartan group showed that the level of fibrotic intensity, distribution, and H-score was decreased compared to the control group. Moreover, the result of Mann Whitney statistic test, for determining the H-score for both groups, showed that p is less than 0.05 (p<0.05), which implies that this research is statistically significant. This research proves that giving Losartan tablets brings a significant impact in reducing the formation of muscle fibrosis in muscle injury grade 1 in gastrocnemius rabbits.

Singapore's HSA recalls contaminated losartan tablets

Singapore's HSA recalls contaminated losartan tablets

New nitrosamine impurity detected in losartan tablets

New nitrosamine impurity detected in losartan tablets

Insertion of Dual Drugs of Hypertension in Gelatin Pockets for Chrono pharmacotherapy and its Evaluation by in-vitro and ex- vivo Studies

Abstract: Objective: The project was aimed to fabricate and evaluate a pulsatile capsule to program the release of dual antihypertensive drugs to mimic the circadian pattern of Blood Pressure. The formulation was optimized to repeatedly release the drug in pulses during the vulnerable period of 4 a.m. to noon upon administration during bed time. Methods: Formulation was prepared by means of Pulsincap technology. It consisted of an insoluble capsule body housing a layer of swellable polymer, a Losartan tablet sealed by an erodible polymer tablet. The system was capsulated in non-biodegradable body capped with water soluble cap containing fast releasing Amlodipine-sorbitol granules. The developed formulation was studied for physical characteristics, lag time determination, in vitro and ex vivo release. Results: The capsule cap dissolved in acidic pH released 99.29% of the amlodipine within 3h. The swellable polymer layer at the base of capsule pushed the plug along with losartan tablet out after a lag time of 6-7 h with 85.93% drug being released at the end of 12 h providing a time controlled need based release. Pulsincap formulated with Amlodipine-Sorbitol granules of G3 formulation, Losartan core tablet of C4 formulation and Erodible tablet of Guar gum with E4 formulation showed highest drug release over the period of 12 h and release was found to be followed Higuchi model kinetics. The present research study results have confirmed that the modified pulsincap of dual drugs is a suitable device for the time dependent and site specific delivery. Conclusion: This approach can be useful for the timed release of a combination antihypertensive medication and may provide effective 24 h control of Blood Pressure in hypertensive patients. The formulation was successfully designed to achieve enhanced bioavailability and dual pulsatile release. Bedtime dosing will more efficiently control the circadian spikes of hypertension in the morning. Key words: Pulsatile capsule, Erodible polymer tablet, Hypertension, Swellable polymer, Losartan Potassium, Amlodipine besylate.

Medication Errors in Patients with Enteral Feeding Tubes in the Intensive Care Unit.

Objective:Most patients admitted to Intensive Care Units (ICU) have problems in using oral medication or ingesting solid forms of drugs. Selecting the most suitable dosage form in such patients is a challenge. The current study was conducted to assess the frequency and types of errors of oral medication administration in patients with enteral feeding tubes or suffering swallowing problems.Methods:A cross-sectional study was performed in the ICU of Shahid Sadoughi Hospital, Yazd, Iran. Patients were assessed for the incidence and types of medication errors occurring in the process of preparation and administration of oral medicines.Findings:Ninety-four patients were involved in this study and 10,250 administrations were observed. Totally, 4753 errors occurred among the studied patients. The most commonly used drugs were pantoprazole tablet, piracetam syrup, and losartan tablet. A total of 128 different types of drugs and nine different oral pharmaceutical preparations were prescribed for the patients. Forty-one (35.34%) out of 116 different solid drugs (except effervescent tablets and powders) could be substituted by liquid or injectable forms. The most common error was the wrong time of administration. Errors of wrong dose preparation and administration accounted for 24.04% and 25.31% of all errors, respectively.Conclusion:In this study, at least three-fourth of the patients experienced medication errors. The occurrence of these errors can greatly impair the quality of the patients’ pharmacotherapy, and more attention should be paid to this issue.

No association between losartan use and acute pancreatitis in hypertensive patients

Background and objectiveClinical evidence is scarce about the relationship between losartan use and acute pancreatitis. We therefore conducted a population-based case–control study using the database from the Taiwan National Health...

Bioequivalence of Losartan/Amlodipine Fixed Dose Combination Tablets (Losanet AM) Compared with Concomitant Administration of Single Components of Losartan and Amlodipine Tablets in Healthy Human Volunteers

A fixed dose combination of losartan, an angiotensin receptor blocker and amlodipine, a calcium channel blocker, can potentially provide complementary mechanism of action to improve blood pressure control and clinical outcomes. The current study was conducted to compare the pharmacokinetics of a new combination product of losartan potassium and amlodipine besylate with separate co-administration of losartan potassium and amlodipine besylate tablets in 40 healthy human volunteers after a single oral dose in a randomized three-period crossover study. The study protocol was prepared in accordance to the requirements set in the EMA guidance for conducting bioequivalence studies. Reference (Cozaar 100 mg, Merck Sharp & Dohme Ltd, UK and Norvasc 10 mg, Pfizer, Canada) and test (Losanet AM, Pharmaline, Lebanon) drugs were administered to fasted volunteers and blood samples were collected up to 168 hours and assayed for losartan, carboxylic acid losartan metabolite and amlodipine using a validated LC-MS/MS method. The pharmacokinetic parameters AUC0-t, AUC0- ∞,Cmax, Tmax, T1/2, MRTinf, residual area (%) and elimination rate constant were determined from plasma concentration-time profile by non-compartmental analysis method using WinNonlin V5.3. The analysis of variance did not show any significant difference between the two formulations and 90% confidence intervals fell within the acceptable range for bioequivalence (80-125%). The resulting data demonstrated that when administered as fixed dose combination or individual tablets, the pharmacokinetics of losartan and amlodipine were bioequivalent and were well-tolerated.

Bioequivalence study of two Losartan tablet formulations with special emphasis on cardiac safety

To study the bioequivalence of Losartan Potassium Tablets 50 mg manufactured by Micro Labs Ltd. India to Cozaar® Tablets 50 mg, manufactured by Merck Sharp and Dohme Ltd., UK in normal healthy adult subjects under fasting condition along with the comparative safety evaluation of both treatments. The in vitro dissolution studies were carried out on 12 units each of test and reference products using the paddle method and dissolution media like water, 0.1 N hydrochloric acid with pH 1.2, pH 4.5 acetate buffer and pH 6.8 phosphate buffer. An open label, randomized, two-treatment, two-period, two-sequence, crossover bioequivalence study with a washout period of 7 days was conducted in 60 healthy Indian male subjects. Serial blood samples were collected after drug administration in each study period. Plasma concentrations of losartan and losartan acid were determined using a validated LC-MS-MS method. The pharmacokinetic parameters of losartan and losartan acid were determined using a non compartmental model. Occurrence of adverse events, change in systolic blood pressure, diastolic blood pressure, heart rate and QT interval from the baseline to 3.50 h post dose were studied and compared between the two treatments as safety parameters. The in vitro study proved the essential similarity of both the formulations as evident from the similarity factor of > 50% in all the dissolution media. The ratios for geometric least square means and 90% confidence intervals were within the acceptance criteria of 80% to 125% for log transformed C(max), AUC(0-t) and AUC(0-∞) for losartan. No statistically significant difference between the two treatments was observed for either of the safety parameters. The test product Losartan Potassium tablets 50 mg manufactured by Micro Labs Limited, India was bioequivalent to Cozaar® tablets 50 mg, manufactured by Merck Sharp and Dohme Ltd., UK in terms of rate and extent of absorption. Both treatments were well tolerated and had similar non significant effect on the safety parameters.

Pharmacokinetics of Hydrochlorothiazide, Losartan and E3174 after Oral Doses of Losartan and Losartan/Hydrochlorothiazide in Healthy Chinese Male Volunteers

Aims: A simple and highly sensitive LC-MS method was used to determine the concentrations of losartan, its major active metabolite E3174 and hydrochlorothiazide in human plasma and pharmacokinetic characteristics and metabolism phenotype observation after administration of losartan tablets and losartan/hydrochlorothiazide combination tablets. Methods: An open, randomized cross-over single-dose study was designed in forty healthy male volunteers, A single-dose of 50 mg losartan tablets or 50 mg losartan/12.5 mg hydrochlorothiazide combination tablets was orally given and blood samples were collected at scheduled time. A LC-MS method was established and evaluated for determining the plasma concentrations of losartan, E3174 and hydrochlorothiazide. The pharmacokinetic parameters and characteristic of metabolism phenotypes were calculated and compared via this test. Results: The elimination rate of E3174 (t1/2) was significantly shorter (P 0–t was lower (P 1/2, AUC0–t and AUC0–inf of E3174.

Combination of Losartan and Hydrochlorothiazide: In vivo Bioequivalence

Two trials were performed in different groups of volunteers with the aim to compare the bioavailability of 50 mg losartan tablets (Sarvas as test and an originator product as reference formulation; study 1) and losartan/hydrochlorothiazide (50 mg/12.5 mg) (CAS 124750-99-8/CAS 58-93-5) combined formulations (Sarvastan as test and an originator product as reference formulation; study 2), respectively. Each study was conducted according to an open, randomized, single-dose, two-period cross-over design in 24 healthy volunteers with a wash-out period from 7 to 14 days. Blood samples were taken up to 36 h in the first study and up to 48 h in the second study. Concentrations of losartan and its principal active metabolite, i.e. E3174, as well as hydrochlorothiazide were determined by HPLC or LC-MS-MS, respectively. In the first study, the 90% confidence interval for intra-individual ratios of AUC0-t and Cmax of losartan were between 0.91 and 1.03 (AUC0-t) as well as between 0.87 and 1.19 (Cmax), and thus within the acceptance ranges. The 90% confidence interval for intra-individual ratios of AUC0-t, and Cmax of E3174 were between 0.90 and 1.13 for AUC0-t, and between 0.97 and 1.14 for Cmax. In the second study, i.e. after administration of combined losartan/hydrochlorothiazide formulations, the 90% confidence interval for intra-individual ratios of AUC0-t and Cmax of losartan were between 0.90 and 1.04 (AUC0-t) as well as between 0.86 and 1.20 (Cmax). Similarly to the parent compound, no significant differences of bioavailability parameters of E3174 between the two studied formulations were found. The 90% confidence interval for intra-individual ratios of AUC0-t and Cmax of hydrochlorothiazide were between 0.89 and 0.98 (AUC0-t) as well as between 0.82 and 1.00 (Cmax). In the light of the present studies it can be concluded that the losartan as well as losartan/hydrochlorothiazide test formulations are bioequivalent to the respective reference formulations.

코자 정(로자탄 칼륨 50 mg)에 대한 로자르탄 정의 생물학적동등성

The purpose of the present study was to evaluate the bioequivalence of two losartan tablets, tablet (MSD Korea. Co., Ltd., Seoul, Korea, reference drug) and tablet (DaeWon Pharm. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received two tablets at the losartan kalium dose of 100 mg in a crossover study. There was a one-week washout period between the doses. Plasma concentrations of losartan were monitored by an LC-MS/MS for over a period of 12 hr after the administration. (the area under the plasma concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. (maximum plasma drug concentration) and (time to reach ) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed and . No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the ratio and the ratio for were , respectively. These values were within the acceptable bioequivalence intervals of . Taken together, our study demonstrated the bioequivalence of and with respect to the rate and extent of absorption.

Lercanidipine and Losartan Effects on Blood Pressure and Fibrinolytic Parameters

Antihypertensive agents may modulate fibrinolysis in addition to reducing blood pressure. We conducted a randomized trial to assess the effects of lercanidipine and losartan on blood pressure (BP) lowering and three fibrinolytic parameters: plasminogen activator inhibitor-1 (PAI-1), D-dimer, and fibrinogen. All patients enrolled had essential hypertension and underwent a placebo run-in period of 2 weeks before randomization to either lercanidipine tablets 10-20 mg once daily or losartan tablets 50-100 mg once daily. Twenty-six patients completed this study. After 8 weeks of treatment, both groups of patients had significantly reduced systolic (SBP) and diastolic BP (DBP) (SBP, p = 0.034 and 0.050, respectively; DBP, p = 0.018 and 0.034 for lercanidipine and losartan, respectively). Both drugs were well tolerated. Only in the group treated with lercanidipine was PAI-1 concentration significantly reduced (57.1 +/- 4.7 to 43.1 +/- 4.8 ng/mL, p = 0.047). No difference was found with D-dimer and fibrinogen in either group. This study shows that both lercanidipine and losartan are effective antihypertensive drugs in patients with essential hypertension. Lercanidipine may provide additional benefit in fibrinolysis.

Identification of losartan degradates in stressed tablets by LC-MS and LC-MS/MS

Three unknown peaks were observed in the severely stressed losartan tablets (at 40°C and 75% relative humidity for 3 years) analyzed by a stability indicating HPLC method. The sample solutions were subjected to liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis to obtain the chemical identities of these potential degradates. High accuracy and sensitivity of losartan and its degradates were obtained by using atmospheric pressure chemical ionization (APCI) technique in the LC-MS/MS analysis. Three trace level degradates (≤0.1%) were found to be the aldehyde and dimeric derivatives of losartan. The structural assignment was further confirmed by comparing the tandem mass spectra of the unknowns with those of the authentic materials of each corresponding degradate. Finally, the mechanistic pathways for the formation of the dimers are discussed.