Formulation and in vitro evaluation of directly compressed controlled release tablets designed from the Co-precipitates

Controlled release dosage forms provide sustained therapeutics effects for prolonged period of time and improve patient compliance. In present study, controlled release co-precipitates of Metoprolol Tartrate and Losartan Potassium were prepared by solvent evaporation method using polymers such as Eudragit RL 100 and Carbopol 974PNF and controlled release tablets were directly compressed into tablets. In-vitro dissolution of controlled release coprecipitates were performed by USP Method-II [paddle method] and tablets were evaluated by USP Method-I [rotating basket method] in phosphate buffer [PH 6.8] using pharma test dissolution apparatus. The temperature was maintained constant at 37 +/- 1.0 0 C and the rotation speed of paddle and basket was kept constant at 100rpm. Drug release mechanisms were determined by applying Power Law kinetic model. The difference and similarity of dissolution profiles test formulations with reference standards were also determined by applying difference factor [f1] and similarity factor [f2]. The results showed that the controlled release co-precipitates with polymer Eudragit RL 100 of both the drug extended the drug release rates for 10 hours and those having polymer Carbopol 974P NF extended the drug release rates for 12 hours. The controlled release tablets prepared from controlled release co-precipitates extended the drugs release up to 24 hours with both the polymers. The drug was released by all tests anomalous non fickian mechanism except F1 and F5 do not follow Power Law. The f1 and f2 values obtained were not in acceptable limits except F15 whose values were in acceptable limits. It is concluded from the present study that polymers [Eudragit RL 100 and Carbopol 974P NF] can be efficiently used in development of controlled release dosage forms having predictable kinetics

Interaction of palladium inorganic salt and organic complex with glutathione content of liver homogenate

Glutathione is an essential antioxidant of living organism that provides a primary protection against metals toxicity. A significant amount of glutathione is present in blood erythrocytes, plasma and liver hepatocytes to protect them from oxidative damage from both external and internal oxidants. Metalo-element palladium has numerous pharmacological, clinical and toxicological compensations, like palladium is used as anti-viral, anti-bacterial, neuroprotective and anti-tumor agent. However studies have also indicated some mild to serious toxic effects of palladium metallo-elements. In the presence study the interaction of palladium inorganic salt and organic complex with glutathione [GSH] content of liver homogenate was examined spectro-photometrically. 20% [w/v] liver homogenate was prepared of the collected liver of rabbit in 5% TCA [tri-chloro-acetic acid] solution and 1mm EDTA, using a potter-eveljhem homogenizer with motor driven Teflon pestle. The GSH content quantification was carried out by Elman's method. Our finding showed that there was a depletion of GSH content by both palladium inorganic salts and organic complexes, concentrations wise as well as with time elapse as level of GSH content decrease from [43.6% to 72.62%] with Palladium Nitrate and from [24.09 to 59.5%] with Bis-benzonitrile Palladium II Chloride as compared to control, and further dropped with time incubation from 0-90 minutes from [49.7 to 87.1%], with Palladium Nitrate and from [29.3% to 67.6%] respectively. The result showed that the effect of both inorganic salt of palladium was more enhanced as compare to its organic complex. It was suggested from our finding that the depletion in the glutathione content of liver homogenate may be due to oxidation of glutathione or due to glutathione metal abduct formation by both inorganic salt and organic complex of palladium. This study in situ is a model of in vivo

Development of a rapid resolution HPLC method for the quantitative determination of sitagliptin in human plasma

A new high performance liquid chromatography [HPLC] method for the quantitative determination of sitagliptin in human plasma was developed and validated for pharmacokinetics study. The plasma was spiked with the internal standard [Salbutamol, IS], extracted with trichloro acetic acid. The extracted analyte was injected into a Symmetry ODS C18 column [250mm×4.5mm, 5m] and the flourometric detector was operated at 267 nm for excitation and 575 nm for emission. The mobile phase consisting of Potassium dihydrogen phosphate buffer pH [4.9]- Acetonitrile Methanol [30:50:20 v/v] at flow rate of 1.0mL/min. The method showed high specificity. Calibration curves of the peak area ratio of each analyte/IS versus sitagliptin concentration were linear in the range of 0.122-31.25 micro g/mL [r>0.989] for plasma and 0.012-25 ug/ml for QC solution[r>0.995]. The lower limit of quantification [LLOQ] was 0.122microg/mL in plasma and 0.012 in QC solution. The intraday and interday coefficient of variation was lower than 10%. The accuracy [relative recovery] at three levels was 100.95%, 101.03% and 97.79% respectively. The extraction recovery was 97.6%, 92.2% and 91.96% at the concentrations of 6.25, 25 and 100microg/mL, respectively. Short term and long term, freeze thaw stability of standard solutions and plasma samples were satisfactory. The optimized HPLC method was validated and proved to be specific, robust and accurate for determination of Sitagliptin in human plasma

Synthesis, characterization and antihypertensive activity of 2-phenyl substituted benzimidazoles

Hypertension is one of cardiovascular disease that is not sufficiently prevented and controlled at both hospital and community levels. Hypertension resulted in significant morbidity and mortality. The benz-imidazole ring is very important pharmacophore in modern drug discovery. The substituted benzimidazoles are the important for medicinal research. Researchers have reported that substituted Benzimidazoles are the structural isosteres of nucleotides, and easily allow them to interact with the different biopolymers, possess pharmacological activity especially antihypertensive activity. Angiotensin II Receptor Antagonists/Blockers [ARBs] compete with angiotensin II at the receptor site and block the contractile effect of angiotensin II in all vascular smooth muscles. Among all Angiotensin II Receptor Antagonists/Blockers [ARBs], Telmisartan, Milfasartan and many others have benzimidazole ring in their structure. In this study Angiotensin II Receptor Antagonists/Blockers [ARBs] have been prepared. Synthesized compounds were characterized by physical data and FTIR spectroscopic technique. Synthesized compounds studied were finally screened for their antihypertensive activity by tail cuff method of measurement of blood pressure by NIBP apparatus [None Invasive Blood Pressure] using Chart 5.0 software. The compounds synthesized were 2-[3-nitrophenyl]-1Hbenzimidazole [1a], 3-[1H benzimidazol-2-yl]aniline [1b] and 5-[1H-benzimidazol-2-yl]-2-methoxyphenol [1c]. The synthesized compounds have shown antihypertensive activity by taking Losartan as lead compound

Spectrophotometric investigation of Glutathione modulation by Thallium chloride in aqueous medium

Thallium has been shown to significantly influence various tissues of living organisms; Exposure to Thallium can disturb mitochondrial function, degenerate neurons, and interfere with the function of critical metabolic enzymes and co-enzymes. Glutathione [GSH] an essential biomarker is considered a key factor in harnessing the thallium toxicity. In the present study the interaction of Thallium [Thallium Chloride] and glutathione was investigated spectro- photometrically in aqueous media. The renowned Elman's experimental protocol was followed at a wavelength of 412nm for Glutathione quantification in each sample. The pH of each sample was maintained at 7.6 using Phosphate buffer during the entire course of the experiment. A concentration as well as time dependent depletion of glutathione after exposure to various concentration of Thallium metal was observed, revealing chemical interaction between the metal and glutathione. The exact mechanism of interaction of Thallium and glutathione is still to be investigated. However, this piece of research suggests that a decrease in the concentration of Glutathione may be due to Thallium-GSH abduct or oxidize glutathione [GSSG] formation. This study was performed in-vitro as a model of in vivo

role of Glutathione, Cysteine and D-Penicillamine in exchanging Palladium and Vanadium metals from albumin metal complex

Thiol groups are extensively present across biological systems being found in range of small molecules [e.g. Glutathione, Homo-cysteine] and proteins [e.g. albumin, haemo-globin]. Albumin is considered to be a major thiol containing protein present in circulating Plasma. Albumin contains a single thiolate group located at cysteine-34[cys-34] at its active site. Albumin also binds a wide variety of metals and metals complexes at various sites around the protein. Usually heavy metals are preferentially attached with the thiol group of albumin. The binding of heavy metals at cys-34 provides a mechanism by which the residence time of potentially toxic species in the body can be increased. In this research we have assessed the oxidative modification of and metal binding capacity of cys-34 with heavy metals Palladium and Vanadium to investigate the ease with which it is possible to effect disulfide-thiol exchange at this sites/or remove a metal bound at this position. Both the metals were treated with albumin and then the albumin metals [Pd and V] complexes were treated with small thoil molecules like Glutathione, Cysteine and D-Penicillamine. Our finding showed that the albumin thiol group retained the metals with itself by forming some strong bonding with the Thiols group, it is concluded from this finding that if by chance both the metals enter the living system; strongly disturb the chemistry and physiological function of this bio-molecule