Male patients with normal blood sugar levels, patients with only cardiovascular disease without any prior drug therapy. Twenty six healthy volunteers having no history of smoking, alcoholism, any type of diseases were considered as controls. The subjects having age less than 20 years and above 70 years, secondary diabetic patients and patients suffering from renal disease were excluded from the study. The patients were treated with either atorvastatin 40 mg or metoprolol 100mg for at least 10 days.
This method was accurate, specific, linear, precise, and suitable for the analysis of metoprolol and atorvastatin by RP-HPLC method. The HPLC instrument comprised a Waters HPLC with autosampler and UV detector. The Inertsil ODS-3 (4.6×150 mm, 5 µm) column is used. The ratio of mobile phase used is phosphate buffer 4.8 pH: acetonitrile (35:65v/v). Mode of separation is isocratic and its temperature of the column is ambient. The optimized chromatographic conditions are mentioned in Table 1 and chromatograms are shown in Figs. 4-7. Assay
Authors are thankful to Ctx Lifesciences Pvt.Ltd,Valsad,Gujarat and Torrent Pharmaceuticals for gratis sample of Metoprolol succinate and Atorvastatin calcium respectively as well as Sophisticated Instrumentation Center for Applied Research & Testing (SICART), Vallabh Vidyanagar for providing facilities to complete this work successfully.
Calcium is a member of the drug class known as statins, used for lowering blood cholesterol. It also stabilizes plaque and prevents strokes through anti-inflammatory and other mechanisms. Metoprolol Tartarate is an antihypertensive drug, It is a selective β1 receptor blocker used in the treatment of several diseases of the cardiovascular system, especially hypertension. Literature survey revealed that assay for Atorvastatin Calcium as bulk and its dosage form are official in Indian Pharmacopoeia 2007  and for
Three simple, accurate and precise UV-Spectrophotometric methods has been developed and validated for quantitative determination of Atorvastatin calcium (ATS) and Metoprolol succinate (MET) in capsules. First method is based on simultaneous equations and the wavelengths selected for analysis were 246.5 nm (λmax of Atorvastatin calcium) and 276.5 nm (λmax of Metoprolol succinate). Second method involves multicomponent mode of analysis and the wavelengths selected for analysis were same as used in first method. Third method is based on area under curve and the wavelength ranges selected for analysis were 251.5-241.5 nm for Atorvastatin calcium and 281.5-271.5 nm for Metoprolol succinate. Linearity was obtained in the concentration range of 4-24 µg/ml and 10-60 µg/ml for Atorvastatin calcium and Metoprolol succinate, respectively. The results of analysis have been validated statistically and by recovery studies. The utility of the developed methods has been demonstrated by analysis of commercial formulation containing these drugs.
(50–70 mg per tablet). Kollidon SR showed excellent controlled drug release in this range. Formulation MS06 showed optimum drug release of 94.31% at 24 h with f2 value of 74 when compared to marketed formulation (Metpure XL) and complying with USP requirements for release as given in Table 7. Eudragit RS plays a significant role as to control the burst release that occurs in the initial hour. It was observed that formulations MS01, MS02, and MS03 with Kollidon SR polymer and devoid of Eudragit RS, showed a significant burst release effect in the initial 1–2 h of release as compared to the rest of the formulations. The release for formulations MS01, MS02 and MS03 at end of 1 hour was 31.23%, 25.22% and 22.02% respectively which is not in the desired limit of not more than 25% as per USP requirements (Table 7). Kollidon SR, is a polymer containing 80% insoluble PVA and 20% soluble PVP. When in contact of the dissolution media the water soluble PVP dissolves forming pores for release of the dug. The sudden burst effect has been attributed due to this phenomenon. Inclusion of Eudragit RS into the formulation controls the burst release and aids kollidon SR in controlling the drug release over a 24 hour period. For formulations MS05, MS06, MS08 and MS09 containing 10-20mg of Eudragit RS per tablet the release at the end of 1 hour was 22.44%, 16.82%, 21.45% and 10.55% respectively. This clearly envisages the role of Eudragit RS in controlling the burst release which was observed with Kollidon SR alone. The release profile of the optimum batch MS06 of bilayer tablet is depicted in Fig. 4. The Immediate release atorvastatin component releases 100.87% the drug in 45 min whereas the release of metoprolol succinate component is sustained upto 24 h0urr.
A simple, precise and accurate first order derivative spectrophotometric method was developed and validated for the simultaneous estimation of Atorvastatin Calcium, Aspirin, Ramipril and Metoprolol Tartrate in bulk and in combined dosage form. The drugs were identified by the melting point and IR spectrum, the IR spectrum of Atorvastatin Calcium, Ramipril, Metoprolol Tartrate and Aspirin were given in figures 1, 2, 3 and 4, respectively. The solubility of drugs in various polar and non polar solvents checked as per I.P guidelines. All the drugs were exhibited different solubility characters. From the solubility data, the common solvents were found to be methanol, acetonitrile, acetone, dichloromethane and alkaline borate buffer (pH 9). The solvents such as acetonitrile, acetone, dichloromethane and alkaline borate buffer (pH 9) were not selected because the cut off wavelength of these solutions were above 240 nm and the solvent interference should be expected during the analysis. Hence, methanol was selected as the common solvent and it was used for the preparation of stock solution. Further dilutions were made with distilled water. The solubility profile of Atorvastatin Calcium, Aspirin, Ramipril and Metoprolol Tartrate were given in tables 1, 2, 3, and 4, respectively.
Pure Samples of Aspirin (ASP) Atorvastatin (ATV), Ramipril (RMP) and Metoprolol Succinate (MTP) with purity more than 99.5% were kindly supplied by USP India (P) limited, Hyderabad, India (Figure 1). Zycad Polypill kits were purchased from the Market. HPLC grade Acetonitrile, Perchloric acid and triethylamine was purchased from Merck Germany. Milli-Q water prepared by using Millipore purification system.
Perform analysis. Results: Age groups 51-60years (38.66%) were found to be more likely to IHD. In this study, we finds that. (Aspirin and Clopidogrel) antiplatelet,(nitrglycerine as antiangina,(metoprolol) as (beta blocker antihypertensive), atorvastatin as lipid lowering agent and enoxaparin as anticoagulant agent were mostly prescribed in this hospital. Conclusions: Aspirin , Clopidogrel (antiplateleta), nitrglycerine as antiangina, metoprolol as beta blocker (antihypertensive) and atorvastatin as lipid lowering agent and enoxaparin as antcoagulant agent were frequently prescribed in this hospital and data were analyzed based on different focused updates of ACC/AHA guidelines for the management of patients with stable ischemic heart disease.
Pharmaceuticals in wastewater have clearly raised concern and a broad range of analytical methods has been used to assess the risk as accurately as possible. The aim of our study was to measure and compare the concentrations of atorvastatin, bisoprolol, carbamazepine, ciprofloxacin, clofibric acid, diclofenac, fluoxetine, metoprolol, and sertraline in wastewater samples taken from one municipal and one hospital wastewater treatment plant in Slovenia and to predict the potential environmental burden using the risk quotient. In both effluents only clofibric acid and fluoxetine were not detected. The measured concentrations of the remaining seven pharmaceuticals varied between the ng L -1 and the µg L -1 range. Hospital
parameters like Molar absorptivity, Sandell’s sensitivity, Correlation coefficient, Slope, Intercept, LOD and LOQ were calculated. The correlation coefficient for all the four drugs was found to be above 0.999. Hence all the drugs obey Beer’s law and the concentrations were found to be linear. The calibration graph for Atorvastatin Calcium at 291.5 nm. The calibration curves for Atorvastatin Calcium and Aspirin at 247 nm, respectively. The calibration curves for Atorvastatin Calcium, Aspirin and Ramipril at 242.5 nm, respectively. At 229.5 nm, the calibration curves for Atorvastatin Calcium, Aspirin, Ramipril and Metoprolol Tartrate are shown in figure 6 respectively. The optical characteristics of the drugs at their selected wavelengths are shown in table 1 respectively. The developed method was applied and validated for the analysis of synthetic mixture the amount of Atorvastatin Calcium, Aspirin, Ramipril and Metoprolol Tartrate were found to be in the range of 98.00 - 100.87%, 98.16 - 100.36%, 99.22 - 100.84% and 100.23 – 101.21%, respectively. The results are listed in table 2. The amount found was good agreement with the expected concentration. Hence it was planned to apply for the analysis of formulation. The percentage purity of the drugs in the formulation was found to be 102.76 ± 1.4487, 99.00 ± 1.5795, 99.95 ± 1.7250 and 98.66 ± 0.8496 for Atorvastatin Calcium, Aspirin, Ramipril, and Metoprolol Tartrate, respectively. The results are listed in table 3.The confidence interval for drugs was found to be in the range of 101.23 – 104.28, 97.34 – 100.65, 98.13 – 101.76 and 97.76 – 99.55 for Atorvastatin Calcium, Aspirin, Ramipril, and Metoprolol Tartrate, respectively.
CoA) reductase, which contributes to biosynthesizing cholesterol, is inhibited by these medicines. More than 90% of atorvastatin is attached to plasma proteins. Around 70% of the whole plasma HMG-CoA action is ascribed to atorvastatin active metabolites, even if the concentration of the metabolites is too low. Pharmacokinetic researches and those of the mechanisms of the drug to drug interaction have been attracted by data of real plasma concentration of atorvastatin [1-4]. The chromatographic method is the initial option for determining ATR residues in biological fluids (e.g., blood serum or plasma, & urine) [5-7]. Disadvantages of the chromatographic test are that it is expensive, time-consuming, requires qualified operators, sample pre-treatment (e.g., pre-concentration) for low amounts of drugs, and so forth. Other analytical procedures were suggested, including potentiometry, voltammetry, and spectrometry [8-13].
Since oral bioavailability of atenolol and metoprolol tartrate is poor, different matrix –type transdermal patches incorporating atenolol and metoprolol tartrate were formulated with an objective to study the effect of polymers on transdermal release of the drugs. The polymers selected were polyvinylpyrrolidone, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate and ethyl cellulose. The patches were formulated using combination of polymers and propylene glycol and 1,8-cineole as plasticizer and penetration enhancer, respectively. The physico- chemical evaluation of the polymer matrices was performed for suitability. The interaction among various components of the matrices was studied by performing Differential Scanning Calorimetry and Scanning Electron Micrography of the formulated patches. In vitro permeation studies were performed using rat abdominal skin as the permeating membrane in Keshary-Chien cell. The results indicated that maximum release was obtained at 48 h (85% and 44% of atenolol and metoprolol tartrate, respectively). The drug permeation studies across cadaver skin showed about 27% of reduction in the amount of drug release as that compared to rat abdominal skin was used.
discounted price with the same efficacy will ensure that the hypertensive patients do not go without medications due to lack of insurance. The rising cost of prescription drugs presents a significant challenge to individual con- sumers. Finding affordable treatment options has become a very important need to reduce financial burden on both patients and payers. Future research should be carried out to produce more evidence towards economic comparison of different dosage forms of widely prescribed drugs such as metoprolol using diverse patient populations to generate potential cost savings without compromising health outcomes.
A simple, economical and robust analytical high-performance liquid chromatography-ultraviolet method was developed and validated for simultaneous chromatographic elution of two cardiovascular drugs viz. amlodipine and atorvastatin in biological fluid for the first time. Only two liquid chromatography–mass spectrometry/mass spectrometry methods are available in literature for quantitation of selected pair of analytes. The bioanalytical method was developed in rat plasma by using Thermo beta-basic C 18 (100×4.6 mm, 5 μm) and mobile phase was composed of dibasic phosphate buffer (pH 3.0):acetonitrile in the ratio of 55:45 at a flow rate of 1 ml/min with ultraviolet detection monitored at 240 nm. The selected chromatographic conditions were found to effectively separate amlodipine (5.1 min) and atorvastatin (12.1 min). The parametric statistics, i.e. correlation coefficient of 0.999, was assessed for both the drugs having linearity over the tested concentration range (0.05 to 10.0 μg/ml) in rat plasma using an unweighted calibration curve. The mean recovery (%) was more than 92.8% for both the drugs using protein precipitation method. The accuracy of samples for six replicate measurements at lower limit of quantitation level was within limit. The method was validated and was successfully applied to the nonclinical pharmacokinetic study of combination tablets containing amlodipine and atorvastatin in six Sprague Dawley rats. Key words: Amlodipine, atorvastatin, cardiovascular drugs, simultaneous, high-performance liquid chromatography-ultraviolet, rat plasma, pharmacokinetic
As could be expected in thermal degrada- tion, temperature has the biggest impact (Fig. 2C). This kind of effect was expected because it is known that kinetic constants have exponential de- pendency with reaction temperature (Arrhenius law) and this has also been reported by other au- thors . Therefore, in this case, further investi- gations were not performed. The obtained results imply confirmation of the well-known behavior of atorvastatin at elevated temperatures.
An estimated 5 million people in the USA have HF and more than 550 000 people are diagnosed with this condi- tion each year. 33 34 During the past two decades, based on impressive RCT data, BBs have become one of the most important pharmacological treatments for improv- ing the CV prognosis for patients with systolic HF. It has been shown that the most frequently prescribed BBs in patients with HF in the USA and in Europe are metopro- lol and atenolol. 35 36 Among 11 326 adults who survived a hospitalisation for HF, pharmacy records revealed that the most commonly prescribed BBs in descending order were metoprolol tartrate (43.2%), atenolol (38.5%), car- vedilol (11.6%) and other BBs (6.7%). 36 A recent national prescription audit of BBs dispensed in the USA in 2011 indicated that the most commonly prescribed BBs in descending order are metoprolol tartrate/succin- ate (71.9 million), atenolol (36.3 million), carvedilol (24 million), nebivolol (15 million) and bisoprolol (9 million; ﬁ gure 1). Disturbingly, these BB choices in the patients with HF are not evidence-based.
Glipizide, Gliclazide and Atorvastatin were procured from Matrix laboratories as a gift sample. Streptozotocin (STZ) was purchased from Sigma Chemical Co. The glucose estimation (GOD- POD) kit (excel diagnostic, Hyderabad) was procured from drug store. All HPLC grade solvents (methanol and water) were procured from drug store. All other chemicals including potassium dihydrogen ortho phosphate, sodium citrate, sodium carboxy methyl cellulose, phosphoric acid, DMSO, glucose, concentrated hydrochloric acid, magnesium sulphate, potassium hydroxide, calcium chloride, diethyl ether were procured from finar chemicals Ltd., Ahmadabad. All chemicals used were analytical grade.
I, DR.M.VIJAYALAKSHMI solemnly declare that the dissertation titled A PROSPECTIVE COMPARATIVE CLINICAL STUDY OF ATORVASTATIN AND ATORVASTATIN WITH VITAMIN D3 ON LIPID PROFILE IN VARIOUS PATIENT POPULATION has been prepared by me under the able guidance and supervision of DR.R.PARAMESWARI M.D, Director and Professor, Institute of Pharmacology, Madurai Medical College, Madurai , in partial fulfillment of the regulation for the award of M.D Pharmacology degree examination of the Tamilnadu Dr.MGR Medical University, Chennai to be held in April 2015. This work has not formed the basis for the award of any degree or diploma to me, previously from any other university to anyone.
The effect of combination of statin plus clopidogrel on platelet activity have aroused people’s concern. Lau et al. first reported the negative interference of atorvastatin with the antiplatelet effect of clopidogrel . And some other trials also drove the same result [22, 34, 35]. In contrast, Serebruany et al. showed no difference in platelet inhibi- tory effects of clopidogrel in patients undergoing coronary stent placement taking statins . And other studies [8, 12, 33, 37, 41–43], in accordance with our results, also showed neutral effects of statin on platelet inhibition by clopidogrel. Even more, the main finding of ACHIDO (Atorvastatin and Clopidogrel High DOse in stable pa- tients with residual high platelet activity) study was that high-dose statin improved the pharmacodynamic effects of 150 mg clopidogrel . Possible explanations for this discrepancy could be attributed to the small sample size, lack of strict inclusion criteria, indirect methods for as- sessment of platelet function and different responses to clopidogrel among patients. Patients with diabetes were often low responders to clopidogrel [21, 45, 46].