Simultaneous determination of 6 kinds of N-nitrosamines genotoxic impurities in losartan potassium raw material and its formulations by GC-MS/MS / 中国药房

OBJECTIVE To establish a method for simultaneous determination of the contents of 6 kinds of N-nitrosamines genotoxic impurities in losartan potassium raw material and its formulations. METHODS GC-MS/MS was adopted to determine 6 kinds of N-nitrosamines genotoxic impurities in losartan potassium raw material， Losartan potassium tablet， Losartan potassium capsule and Losartan potassium hydrochlorothiazide tablets， such as N-nitrosodimethylamine （NDMA）， N-nitrosodiethylamine （NDEA）， N-ethyl-N-nitroso-2-propanamine （NEiPA）， N-nitrosodiisopropylamine （NDiPA）， N-nitrosodipropylamine （NDPA） and N-nitrosodibutylamine （NDBA）. The separation was performed on SHIMADZU SH-L-17Sil MS capillary column by temperature- programmed GC， with injector temperature of 250 ℃ ， sample size of 1 μL， carrier gas of helium， and carrier flow rate of 1 mL/min. Electron ionization and multiple reaction monitoring （MRM） data acquisition mode were used， with an ion source temperature of 250 ℃ and solvent delay time of 3.1 min. RESULTS The separation among NDMA， NDEA， NEiPA， NDiPA， NDPA， NDBA and adjacent chromatographic peaks was good， and the separation rate was higher than 3.8； the linear ranges of them were 4.9-486.0， 4.9-488.5， 4.5-451.5， 6.8-683.5， 5.2-525.0 and 5.2-520.0 ng/mL（all r≥0.999 8）. The limits of quantitation were 4.86， 4.88， 4.52， 6.84， 5.25 and 5.20 ng/mL； the limits of detection were 0.97， 0.98， 0.90， 1.37， 1.05 and 1.04 ng/mL. RSDs of repeatability tests were 2.2%-5.6%（n＝6）， those of precision tests were 0.5%-1.4%（n＝6）， and those of stability tests were 1.5%-3.4%（n＝5）， respectively. Average recoveries of low-， medium- and high-concentration solution were 83.4%-103.0% （RSDs were 1.2%-6.3%， n＝3）， respectively. No one among the 6 kinds of N-nitrosamines genotoxic impurities was detected in both losartan potassium raw material and formulations. CONCLUSIONS The method is good in separation effect， highly accurate， sensitive and simple. It can be used in the determination of the 6 kinds of N-nitrosamines genotoxic impurities.

Sustained release matrix tablet of 100 mg losartan potassium: Formulation development and in vitro characterization

Abstract Sustained release matrix tablets of 100 mg losartan potassium HCl were fabricated with two release retarding polymers namely HPMC K100 M and affinisol by direct compression method. Nine trial formulations were prepared by varying content of these polymers, each from 50 mg to 100 mg; keeping the total weight of the tablet 310 mg. The best formulation was selected based on in vitro drug release profile for 12 hours conducted in Type II dissolution apparatus at 50 rpm and water as dissolution medium. Pre-compression parameters such as bulk density, tap density, Carr's index and Hausner ratio were evaluated for the selected tablet. The tablets were subjected to thickness, weight variation test, drug content, hardness and friability. Drug release kinetics, surface morphology and accelerated stability study were investigated for that selected formulation. Formulation F4 with the composition of 75 mg HPMC K100M and 100 mg affinisol was selected as the best formulation that extended the drug release up to 12 hours. Pre-compression parameters and other tableting properties were within the Pharmacopoeia limit. Release kinetics analysis proved non-fickian zero-order drug release and that was further confirmed by surface morphology of the tablets before and after dissolution study visualized by SEM. The developed formulation was found to be stable for one month stored at 60 ○C.

Effect of Haikunshenxi capsule combined with losartan potassium tablets on renal function and inflammatory factors in patients with chronic kidney disease / 中国医师进修杂志

Objective:To investigate the curative effect of Haikunshenxi capsule combined with losartan potassium tablets on chronic kidney disease (CKD) and its effect on renal function and inflammatory factors.Methods:One hundred patients with chronic kidney disease in Shaoxing Central Hospital from January 2018 to December 2019 were selected and randomly divided into observation group (50 cases) and control group (50 cases). The control group was treated with losartan potassium tablets based on conventional therapy, and the observation group was treated with Haikunshenxi capsulebase on control group. The treatment course of the two groups was 12 weeks. The curative effect, renal function, inflammatory factors, 24h urinary protein (24 h Upro) and glomerular filtration rate (GFR) were compared between the two groups before and after treatment.Results:The total effective rate in the observation group was higher than that in the control group: 90.0%(45/50) vs. 72.0%(36/50), χ2 = 5.26, P<0.05. After treatment, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in the two groups were decreased and the levels of Scr and BUN in the observation group were lower than those in the control group: (63.27 ± 2.89) μmol/L vs. (67.89 ± 2.35) μmol/L, (5.23 ± 0.19) mmol/L vs. (5.56 ± 0.16) mmol/L, the differences were statistically significant ( P<0.05). After treatment, the levels of serum C-reactive protein (CRP) , interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the two groups were decreased and the levels of CRP, IL-6 and TNF-α in the observation group were lower than those in the control group: (2.97 ± 0.34) mg/L vs. (3.58 ± 0.42) mg/L, (3.64 ± 0.68) ng/L vs. (4.97 ± 0.96) ng/L, (14.32 ± 2.17) ng/L vs. (17.86 ± 2.06) ng/L, the differences were statistically significant ( P<0.05). After treatment, the level of 24 h Upro in two groups was decreased, while the level of GFR was increased, and the level of 24 h Upro in the observation group was lower than that in the control group: (0.87 ± 0.09) g vs. (1.15 ± 0.13) g , but the level of GFR in the observation group was higher than that in the control group: (101.73 ± 3.12) ml/(min·m 2) vs. (96.75 ± 2.35) ml/(min·m 2), the differences were statistically significant ( P<0.05). Conclusions:Haikunshenxi capsule combined with losartan potassium tablets has obvious curative effect on patients with chronic kidney disease, and can improve renal function and micro inflammation.

Comparación de los perfiles de disolución de los comprimidos de Losartán potásico 100mg nacionales e importados vs precio, Paraguay (2019)

RESUMEN La hipertensión arterial es el principal factor de riesgo cardiovascular, y su prevalencia en Paraguay es la mayor de América Latina. El objetivo del presente trabajo fue comparar productos de losartán de 100 mg comprimidos de producción nacional e importada a través de los perfiles de disolución versus su precio. Se tomaron 8 marcas de losartán potásico comercializadas durante el 2017, realizándose los controles de calidad de acuerdo a lo establecido en la Farmacopea Americana (USP 38). Se determinó el porcentaje de principio activo liberado en el medio de disolución establecido por la USP 38, por medio de los perfiles de disolución. Las determinaciones se realizaron por HPLC y espectrofotometría UV/V. Los controles realizados cumplieron con las especificaciones establecidas por la USP 38. No se encontraron diferencias significativas en el análisis estadístico de los perfiles de disolución de las diferentes marcas analizadas. Los resultados demostraron que los precios de las marcas analizadas no afectaban la calidad de los productos, pero sí en el costo del tratamiento de la población de escasos recursos, debido al mayor costo de los productos importados con respecto a los de producción nacional.

ABSTRACT Hypertension is the main cardiovascular risk factor, and its prevalence in Paraguay is the highest in Latin America. The objective of the present work was to compare products of 100 mg losartan tablets made in Paraguay and imported products, through dissolution profiles versus price. Eight brands of potassic losartan commercialized during 2017 were subjected to quality controls in accordance with the provisions of the American Pharmacopoeia (USP 38). The percentage of active principle released in the dissolution medium established by USP 38 was determined by means of dissolution profiles. The determinations were made by HPLC and UV/V spectrophotometry. The controls carried out complied with the specifications established by USP 38. No significant differences were found in the statistical analysis of the dissolution profiles of the different brands analyzed. The results showed that the prices of the brands analyzed did not affect the quality of the products, but they affected the cost of treatment of the low-income population due to the higher cost of imported products compared to those of national production.

Effect of Modified Fuyuanwan Combined with Auricular Acupressure Bean on Stage Ⅱ， Ⅲ Diabetic Nephropathy and Its Effect on Serum JAK/STAT Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the therapeutic effect of modified Fuyuanwan combined with auricular acupressure bean on stage Ⅱ， Ⅲ diabetic nephropathy and its effect on serum janus kinase （JAK）/ signal transducer and activator of tranions （STAT） signaling pathway. Method:A total of 180 cases were randomly divided into control group and observation group， 90 cases in each group. Losartan potassium， modified Fuyuanwan combined with auricular acupressure bean were given respectively for 12 weeks. Renal function indexes ［blood urea nitrogen （BUN）， serum creatinine （SCr）， urinary albumin excretion rate （UAER）， 24 h urinary protein quantitative （24 h Upor）］， relative abundance of intestinal flora （verruca microflora， scleriobacteriae， deferribacter， proteobacteria）， oxidative stress indicators ［advanced oxidation protein products （AOPPs）， reactive oxygen species （ROS）， glutathione peroxidase （GSH-Px）， total superoxide dismutase （TSOD）］， renal blood flow index ［end-diastolic blood flow velocity （EDV）， peak systolic value （PSV）， pulse index （PI）， blood flow resistance index （RI）］， JAK/STAT signaling pathway ［JAK， phosphorylated JAK （p-JAK）， STAT， phosphorylated STAT （p-STAT） were observed before and after treatment. The safety indexes of two groups were evaluated after treatment. The efficacy was observed after treatment and followed up for 1 years and 2 years. Result:After treatment and follow-up for 1， 2 years， the total effective rates of patients in observation group were 97.8% （87/89）， 81.6% （71/87）， 59.8% （49/82）， respectively， observation group which were significantly higher than those in control group of 79.3%（69/87），57.8%（48/83），37.2%（29/78） （<italic>χ</italic>²=4.016， <italic>χ</italic>²=4.503， <italic>χ</italic>²=4.769， <italic>P</italic><0.05）. Compared with control group after treatment， UAER， BUN， SCr， 24 h Upor， firmicutes， actinobacillus， proteobacteria， AOPPs， ROS， PI， RI， p-JAK， p-STAT3 in observation group were significantly decreased （<italic>P</italic><0.05，<italic>P</italic><0.01）， microflora verruca， GSH-PX， TSOD， JAK， STAT3 were significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）， EDV and PSV were significantly accelerated （<italic>P</italic><0.05，<italic>P</italic><0.01）. The incidence of adverse reactions was 1.1% （1/89） in observation group， lower than 13.8% （12/87） in control group （<italic>χ</italic>²=5.127， <italic>P</italic><0.05）. Conclusion:Modified Fuyuanwan combined with auricular acupressure bean can significantly improve the curative effect of stage Ⅱ， Ⅲ diabetic nephropathy， and its mechanism of action may be related to the serum JAK/STAT signaling pathway.

Determination of N-Nitroso-N-Methyl-4-Aminobutyric Acid in Losartan Potassium Using High Performance Liquid Chromatography Triple Quadrupole Mass Spectrometry / 中国药学杂志

OBJECTIVE: To establish a method to determine the genotoxic impurity, N-nitroso-N-methyl-4-aminobytyric acid, in losartan potassium using high performance liquid chromatography triple quadrupole mass spectrometry (HPLC-MS/MS). METHODS: The method was developed by using Shimadzu Shim-pack XR-ODS II column (2.0 mm×150 mm, 2.2 μm). Time program was conducted with mobile phase consisting of water (0.1% formic acid, A) and methanol (B). The flow rate was 0.3 mL•min-1, and the column oven temperature was maintained at 40 ℃. The samples were ionized by electrospray ionization (ESI) with multi reaction monitoring (MRM) data acquisition mode. The collision energies were -11, -13, and -13 V, CID gas was argon with pressure of 270 kPa.3 pairs of precursor, and product ions (m/z) of NMBA were 147.15→117.10, 147.15→87.10, and 147.15→44.10, respectively. RESULTS: The genotoxic impurity NMBA showed linearity between 1 and 100 ng•mL-1 with correlation coefficient of 0.999 9. The intra-day and inter-day repeatability was examined by relative standard deviations (RSDs) of retention time and peak area (RSD<1.10%, n=6 for intra-day repeatability and n=18 for inter-day repeatability). The accuracy was examined by percent recovery at three concentration levels, and the average percent recovery was between 94.40% and 98.04%. CONCLUSION: The established LC-MS/MS method is efficient for limit test and quantitation of NMBA in losartan potassium bulk drug.

Development and evaluation of liquid oral controlled release systems for Losartan potassium

Losartan potassium is a water soluble antihypertensive agent with short half-life. Controlling its release will improvepatient compliance. The benefit will be extended for geriatric patients if the developed system was liquid. The objectiveof this work was to develop controlled release oral liquid losartan potassium. This employed a combination of in situgelation and coating drug particles with pH-dependent polymer (Eudragit® L100). Solid dispersion (SD) prepared at1:1, 1:1.5, and 1:2 drug : polymer ratios, respectively. Sodium alginate solution was loaded with either pure drug orSD, in presence and absence of 1% w/v chitosan. These systems were evaluated for the drug release using continuouspH variation study. Alginate formulation with pure drug underwent in situ gelation in the gastric conditions but lost thegelling strength in the intestinal phase with burst drug release. Loading the formulation with SD resulted in controlleddrug release both in the gastric and intestinal phases. Increasing eudragit concentration in SD decreased the drugreleased with total release efficiency of 62.1%, 53.0%, and 41.7%. Incorporation of chitosan at reduced further drugrelease rate reaching 21% at the higher eudragit concentration. The study provided the formulator with a range of oralliquid formulations for controlled release of losartan potassium.

Clinical Observation of Yishen Huashi Granules Combined with Losartan Potassium Tablets in the Treat-ment of Chronic Glomerulonephritis / 中国药房

OBJECTIVE:To observe the effects of Yishen huashi granules combined with Losartan potassium tablets on renal function indexes and inflammatory factors of patients with chronic glomerulonephritis. METHODS:A total of 107 patients with chronic glomerulonephritis in our hospital during Jan. 2015-Aug. 2016 were divided into observation group(53 cases)and control group(54 cases)according to therapy plan. Besides basic therapy,control group was given Losartan potassium tablets 50 mg,po, qd;observation group was additionally given Yishen huashi granules 10 g,po,tid,on the basis of control group. Both groups were treated for consecutive 2 mouths. Clinical efficacies,renal function indexes(Scr,BUN,24 h urine protein quantification,urine red blood cell)and inflammatory factors(IL-13,CRP,TNF-α)levels were all observed in 2 groups,and the occurrence of ADR was recorded. RESULTS:Clinical total response rate of observation group(86.79%)was significantly higher than that of control group(66.67%),with statistical significance(P<0.05). Before treatment,there was no statistical significance in renal function in-dexes or inflammatory factors levels between 2 groups(P>0.05).After treatment,renal function indexes and inflammatory factors levels of 2 groups were significantly decreased;and observation group was significantly lower than control group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups during treatment. CONCLUSIONS:Yishen huashi granules com-bined with Losartan potassium tablets in the treatment of chronic glomerulonephritis can improve renal function and reduce inflam-mation factor level with good safety.

Similarity Evaluation of the Dissolution Curves of Generic and Original Preparation of Losartan Potassium Tablets / 中国药房

OBJECTIVE:To evaluate the dissolution curves similarity of generic and original preparation of Losartan potassium tablets,and to provide reference for improving quality evaluation of the preparation.METHODS:Using hydrochloric acid solution (pH 3.0),phosphate buffer solution(pH 4.5),phosphate buffer solution (pH 6.8) and water as medium,paddle method was adopted for dissolution test with dissolution medium volume of 900 mL and rotation speed of 50 r/min.UV-visible spectrophotometry was adopted to determine accumulative dissolution of generic and original preparation of Losartan potassium tablets with the detection wavelength of 256 um.The similarity of dissolution curves were evaluated by calculating similarity factor(f2).RESULTS:The linear range of losartan potassium was 12.11-35.96 μg/mL (r≥0.999 7).RSDs of precision,stability and reproducibility tests were all lower than 5.0％.The recoveries of 4 dissolution media were 98.66％-100.84％ (RSD=0.77％,n=9),98.91％-100.59％ (RSD=0.49％,n=9),98.33％-101.39％ (RSD=0.85％,n=9),99.46％-101.32％ (RSD=0.55％,n=9).In 4 dissolution media,f2 of the dissolution curves of 3 batches of generic and original preparation of Losartan potassium tablets were all higher than 70.CONCLUSIONS:The dissolution curves of self-made and original preparation of Losartan potassium tablets show good similarity.

Curative effects of alfacalcidol combined with losartan potassium tablets in the treatment of early diabetic ;nephropathy / 中国基层医药

Objective To discuss the curative effects of alfacalcidol combined with losartan potassium tablets in the treatment of early diabetic nephropathy (EDN).Methods 90 EDN patients in our hospital were chosen and randomly divided into the observation group and control group (45 cases in each group).The control group was given losartan potassium tablets treatment,while the observation group was given alfacalcidol combiend with telmisartan treatment.All the two groups were treated for 3 months.Before and after treatment,the fasting blood glucose (FBG), 24h urine trace albumin quantitative (UAER),24h urine protein (24h pro),serum creatinine (SCr),25 -hydroxyl vitamin D [2 5 (OH )D ],blood calcium (Ca2+),potassium (K+),glycosylated hemoglobin (HbA 1 C )and serum inflammatory factors[C-reactive protein (CRP),tumor necrosis factor alpha (TNF-α),interleukin-6 (IL-6 )] were observed,and the correlation between 25 (OH)D and UAER,24h pro was analyzed.At the same time,the clinical curative effects and adverse reactions during treatment were evaluated.Results In the observation group,the total effective rate was 93.3%,which was significantly higher than 71.1% in the control group (χ2 =7.601,P0.05).After treatment,Scr,24h pro and UAER in the two groups were all significantly reduced compared with before treatment (P0.331).After treatment,25(OH)D in the observation group decreased significantly compared with before treatment (t=12.000,P0.436).Pearson correlation analysis showed that 25 (OH)D level was negatively correlated with 24h pro and UAER (r=0.483,0.778,all P0.151 ).Conclusion Alfacalcidol combined with losartan potassium tablets can significantly reduce the proteinuria levels of EDN patients and inflammation,which has better clinical curative effects and higher safety.

Clinical Observation of Yishen Huashi Granules Combined with Losartan Potassium Tablets in the Treat-ment of Chronic Glomerulonephritis / 中国药房

OBJECTIVE:To observe the effects of Yishen huashi granules combined with Losartan potassium tablets on renal function indexes and inflammatory factors of patients with chronic glomerulonephritis. METHODS:A total of 107 patients with chronic glomerulonephritis in our hospital during Jan. 2015-Aug. 2016 were divided into observation group(53 cases)and control group(54 cases)according to therapy plan. Besides basic therapy,control group was given Losartan potassium tablets 50 mg,po, qd;observation group was additionally given Yishen huashi granules 10 g,po,tid,on the basis of control group. Both groups were treated for consecutive 2 mouths. Clinical efficacies,renal function indexes(Scr,BUN,24 h urine protein quantification,urine red blood cell)and inflammatory factors(IL-13,CRP,TNF-α)levels were all observed in 2 groups,and the occurrence of ADR was recorded. RESULTS:Clinical total response rate of observation group(86.79%)was significantly higher than that of control group(66.67%),with statistical significance(P<0.05). Before treatment,there was no statistical significance in renal function in-dexes or inflammatory factors levels between 2 groups(P>0.05).After treatment,renal function indexes and inflammatory factors levels of 2 groups were significantly decreased;and observation group was significantly lower than control group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups during treatment. CONCLUSIONS:Yishen huashi granules com-bined with Losartan potassium tablets in the treatment of chronic glomerulonephritis can improve renal function and reduce inflam-mation factor level with good safety.

Protective effects of losartan potassium on 5/6 nephrectomy-induced chronic heart failure in rats / 中国药科大学学报

@#The purpose of this research is to investigate the therapeutic effects of losartan potassium on 5/6 nephrectomy rats with chronic heart failure(CHF)and to explore the mechanism. 24 Rats were randomly divided into three groups namely sham group(Sham), pathology group(Nx)and losartan potassium group(Lst), respectively. CHF model in rats were induced by 5/6 nephrectomy. At the 7th week, rats of Lst group were given losartan potassium(50 mg/L)for consecutive 2 weeks. Then all rats were measured for hemodynamic parameters, cardiac index, creatinine, urea nitrogen in serum, and expressions of CD133, VEGFR2, Sox2, cleaved Caspase-3 and Bcl-2 in heart. Compared with Nx group, rats of Lst group improved cardiac and renal functions: decreased LVDP, LVEDP, cardiac index, creatinine, urea nitrogen and increased LVSP. Furthermore, losartan potassium up-regulated gene expression of CD133, VEGFR2, Sox2 and protein level of Bcl-2, and down-regulated cleaved Caspase-3 protein expression. Results suggest that losartan potassium can improve cardiac function of rats with CHF which may be correlated with mobilizing bone marrow stem cells, increasing endothelial progenitor cells(EPCs)level in heart, repairing endothelial function, and inhibiting myocardial apoptosis.

Clinical observation on combined treatment of chronic nephritis proteinuria,a report of 22 cases / 中国基层医药

Objective To observe the curative effect of Zhengqingfengtongning release tablets and lumbroki-nase enteric -coated capsules and losartan potassium tablets joint for the treatment of chronic nephritis proteinuria, and explore its mechanism.Methods 42 patients with chronic nephritis were randomly divided into two groups. 20 cases in the control group were given losartan potassium tablets,50mg,1 ~2 times a day.22 cases in the treatment group received Zhengqingfengtongning release tablets 120mg,2 times a day,lumbrokinase enteric -coated capsules 600 000u,3 times a day on the basis of the control group.The 24h urine protein,liver and kidney function before and after the treatment were observed.Results 20 days after treatment,24h urinary protein in the treatment group decreased 57.08%,which in the control group decreased 41.59%,the difference was statistically significant (t =2.39,P <0.05).30 days after treatment,24h urinary protein in the treatment group decreased 81.28%,which in the control group decreased 52.34%,the difference was statistically significant (t =3.65,P <0.01 ).Renal function change had no significant difference between the two groups.Conclusion Zhengqingfengtongning release tablets and lumbrokinase enteric -coated capsules combined with losartan potassium tablets in the treatment of chronic nephritis proteinuria work fast,and has good curative effect,less side effects,and is worth to recommend.

Clinical Observation of Lisinopril Combined with Losartan Potassium in the Treatment of Chronic Heart Fail-ure / 中国药房

OBJECTIVE:To observe the efficacy and safety of lisinopril combined with losartan potassium in the treatment of chronic heart failure (CHF). METHODS:72 patients with CHF were randomly divided into observation group and control group. All patients were given salt restriction,diuretics and other conventional treatment. Based on the treatment,control group was orally treated with lisinopril tablets 10 mg,once a day,the dose was increased to 2 times after 1-2 weeks until the maximum dose of 40 mg,orally,once a day. Based on the treatment of control group,observation group was additionally treated with losartan potassi-um tablets 50 mg,orally,once a day. The efficacy was evaluated,and cardiothoracic ratio,LVEDD,LVESD,LVEF,HR,SBP,DBP and incidence of adverse reactions were observed after 2 months treatment. RESULTS:The total effective rate in observation group was significantly higher than control group(P0.05). CONCLUSIONS:Based on the coventional treatment,lisinopril com-bined with losartan potassium has better efficacy than lisinopril in the treatment of CHF,with good safety.

The effects of losartan potassium and simvastatin combination therapy on oxidative stress indicators in diabetic patients on peritoneal dialysis / 天津医药

Objective To explore the effects of losartan potassium and simvastatin combination therapy on oxidative stress indicators in diabetic patients on peritoneal dialysis through 12 weeks observation. Methods Diabetic patients with end-stage nephropathy (n=80) who were treated with continuous ambulatory peritoneal dialysis were randomly divided into two groups:control group who received routine treatment (n=40), treatment group who were given losartan potassium 50 mg, once per day and simvastatin 20 mg, once every night (n=40). HbA1C, Insulin dosage, Oxidative stress indicators(SOD, GSH-PX, MDA and Hcy)were compared between two groups before and after peritoneal dialysis. Results There was no significant difference of HbA1C between the 2 groups before and after treatment(P>0.05). The insulin doses increased be?fore dialysis in both groups after CAPD treatment. It is lower in the treatment group than that in the control group ( P<0.05). The expression levels of GSH-PX and SOD in treatment group were higher while the expressions of Hcy and MDA were lower after treatment. The expressions of GSH-PX and SOD were higher while the expressions of Hcy and MDA were lower in treat?ment group than those in control group when comparing the same time point(P<0.05). GSH-PX expression level was lower while the expressions of MDA and Hcy were higher after dialysis than those before dialysis in control group ( P<0.05). Con?clusion Losartan potassium combined with simvastatin treatment can improve curative effect and oxidative stress indicators in diabetic patients on peritoneal dialysis.

Simple Controlled Release Delivery System for an Anti-hypertensive Drug via Buccal Route.

Objective: This study aims to develop controlled release buccal tablets of losartan potassium based on bioadhesion using direct compression technique. Materials and Methods: The bioadhesive buccal tablets of losartan potassium were prepared after preliminary drug-excipients compatibility studies and micromeretics study for powder blends. The tablets were prepared by direct compression utilizing carbopol 934LR as a primary bioadhesive polymer either with or without chitosan or hydroxypropyl methylcellulose E15LV as secondary polymers. Other excipients included PVP K30 as a binder, magnesium stearate as a lubricant and mannitol as a diluent. The tablets were evaluated for weight variation, thickness and diameter, hardness, friability, drug content, surface pH, Ex-vivo residence time and bioadhesion force, In-vitro swelling and drug release study. The analysis of the release profiles in the light of distinct kinetic models (zero order, first order, Higuchi, Hixson-Crowell and Korsmeyer–Peppas) was carried out. Results and Discussion: The formula containing 40% w/w bioadhesive polymers of carbopol 934LR and chitosan (1:2) was selected as the optimum one based on a ranking methodology and then, it was subjected to Ex-vivo permeation and physical stability study in human saliva. Swelling index was 78.32±1.84% after 7h and tablets showed a neutral surface pH. Ex-vivo residence time was long enough for more than 10h. Ex-vivo bioadhesion force was 0.38±0.01N. Drug release was 57.64±3.43% after 8h following zero order kinetics with a steady state permeation flux of 0.959mg/cm2h. Tablets were physically stable in human saliva. Conclusion: These formulae improved, controlled and prolonged the release of losartan potassium from a buccal bioadhesive system for at least 8h in a simple way which can achieve a high patient compliance.

Simultaneous HPLC-MS/MS determination of losartan potassium and its metabolite E-3174 in human plasma and its application to pharmacokinetic study / 中国药学杂志

OBJECTIVE: To develop a sensitive and rapid HPLC-MS/MS method for the determination of losartan potassium and E-3174 in human plasma. METHODS: The plasma samples were extracted with methyl tert-butyl ether (MTBE) after addition of internal standard and acetic acid, and then analyzed with API 3000 LC-MS/MS system. The analytical column was SHISEIDO, CAP-CELL PAK C18 MG II (2.0 mm × 50 mm, 5 μm) and the column temperature was room temperature. The mobile phase was composed of 0.1% formic acid in water (containing 5 mmol·L-1 ammonium acetate) -0.1% formic acid in acetonitrile (20:80) and the flow rate was 0.85 mL·min-1. Detection was performed with multiple reactions monitoring (MRM) using positive electrospray ionization (ESI). RESULTS: The calibration curves were linear over the concentration ranges of 10.10-2525 ng·mL-1 for losartan potassium and 9.820-2455 ng·mL-1 for E-3174, respectively. The lower-limit-of-quantifications were 10.10 ng·mL-1 for losartan potassium and 9.820 ng·mL-1 for E-3174, respectively. Inter-and intra-day precisions were less than 9.22% and accuracy was within 93.56%-102.88%. Extraction recoveries were around 70% and the analytes were proved to be stable. Total run time of an analyte was only 2.5 min. The relative bioavailabilities of the two preparations were 96.5% for losartan potassium and 110.0% for E-3174. These two losartan potassium preparations were bioequivalent. CONCLUSION: This method is rapid, sensitive, specific and applicable to the pharmacokinetic study in human and bioequivalence study of losartan potassium.

Interaction of Losartan potassium with the micelles of Triton X 100.

This study is an investigation of the physicochemical interaction of Losartan potassium (LST K), an angiotensin-II receptor (type AT1) antagonist, with micelles of triton X, a nonionic surfactant. The effect of micelles on the spectral properties of LSTK was monitored on at pH 7.4 and at room temperature. The spectrum of LST K showed gradual and progressive bathochromic and hypochromic shift in presence of increasing concentrations of triton X 100. The binding constant Kb of LST K to triton X 100 micelles was calculated using the differential absorbance at λ = 225 nm& was found to be 4.13 ± 0.35 ×105 mol-1 L. By using pseudo-phase model, the partition coefficient between the bulk water and Triton X 100 micelles, Kx, was calculated from both differential absorbance Δ A225, Kx = 2.26 ±0.12 x105 mol-1 L. The binding of LST K to Triton X 100 micelles implied a shift in drug acidity constant (Δ pKa = 0.8).

Development and evaluation of sustained release losartan potassium matrix tablet using kollidon SR as release retardant

The present study was undertaken to develop sustained release (SR) matrix tablets of losartan potassium, an angiotensin-II antagonist for the treatment of hypertension. The tablets were prepared by direct compression method, along with Kollidon SR as release retardant polymer. The amount of losartan potassium remains fixed (100 mg) for all the three formulations whereas the amounts of Kollidon SR were 250 mg, 225 mg, and 200 mg for F-1, F-2, and F-3 respectively. The evaluation involves three stages: the micromeritic properties evaluation of granules, physical property studies of tablets, and in-vitro release kinetics studies. The USP apparatus type II was selected to perform the dissolution test, and the dissolution medium was 900 mL phosphate buffer pH 6.8. The test was carried out at 75 rpm, and the temperature was maintained at 37 ºC ± 0.5 ºC. The release kinetics was analyzed using several kinetics models. Higher polymeric content in the matrix decreased the release rate of drug. At lower polymeric level, the rate and extent of drug release were enhanced. All the formulations followed Higuchi release kinetics where the Regression co-efficient (R²) values are 0.958, 0.944, and 0.920 for F-1, F-2, and F-3 respectively, and they exhibited diffusion dominated drug release. Statistically significant (P<0.05) differences were found among the drug release profile from different level of polymeric matrices. The release mechanism changed from non-fickian (n=0.489 for F-1) to fickian (n=0.439 and 0.429 for F-2, and F-3 respectively) as a function of decreasing the polymer concentration. The Mean Dissolution Time (MDT) values were increased with the increase in polymer concentration.

O presente estudo foi realizado para desenvolver (SR) matriz de comprimidos de liberação sustentada de losartana, um antagonista da angiotensina II, para o tratamento da hipertensão arterial. Os comprimidos foram preparados pelo método de compressão direta com Kollidon SR como polímero de liberação lenta. A quantidade de losartana potássica permanece fixa (100 mg) para todas as três formulações enquanto que as quantidades de Kollidon SR foram de 250 mg, 225 mg e 200 mg para F-1, F-2 e F-3, respectivamente. A avaliação envolve três etapas- propriedades micromeríticas dos grânulos, estudo das propriedades físicas dos comprimidos e estudos de cinética de liberação in vitro.. Selecionoou-se o aparelho USP tipo II para realizar o teste de dissolução em meio com 900 mL de tampão fosfato pH 6,8 . O teste foi realizado em 75 rpm e a temperatura foi mantida a 37 ºC ± 0.5 ºC. Analisou-se a cinética de liberação utilizando-se vários modelos cinéticos. Conteúdo mais alto de polímero na matriz reduziu a taxa de liberação do fármaco. Em níveis mais baixos de polímero, a taxa e a extensão de liberação do fármaco foram aumentados. Todas as formulações seguiram a cinética de liberação de Higuchi, em que os valores do coeficiente de regressão (R2) foram 0,958 , 0,944 e 0,920 para F-1, F-2 e F-3, respectivamente, e elas apresentaram liberação do fármaco dominada pela difusão. Encontraram-se diferenças estatisticamente significativas (P<0,05) entre os perfis de liberação do fármaco com diferentes níveis de matrizes poliméricas. O mecanismo de liberação mudou de não-fickiano(n=0,489 para F-1) para fickiano(n=0,439 e 0,429 para F-2 e F-3, respectivamente) em função da diminuição da concentração de polímero. Os valores do Tempo de Dissolução Média (TDM) aumentaram com o aumento da concentração polímero.

Studies on effect of variables by response surface methodology for losartan microspheres.

Microspheres of Losartan potassium were formulated using combination of Ethyl cellulose and Acycoat L30D polymer by solvent evaporation method. A 32 factorial design was used to elucidate the effect of variables viz. the amount of drug and the amount of polymer. Discrete spherical microspheres in the range of 40-50 μm were produced with the encapsulation efficiency of more than 80 %. Polynomial equations and response surface plots were generated for all dependent variables. It was observed that both the factors had significant influence on all dependent variables studied. It was observed that as the amount of polymer increases, the rate of release decreases. So t50 increases and the amount of drug released in 2 h (X120) decreases. Drug polymer interaction study was absent as evidenced by HPLC and FT-IR studies.