Stability Indicating Liquid Chromatographic Method for Simultaneous Determination of Aspirin and Omeprazole.

BACKGROUND: Aspirin combination is prescribed for its thrombolytic activity where gastric ulceration is the major side effect of aspirin which can be prevented by combining it with proton pump inhibitor omeprazole. Present study describes development of analytical method for the estimation of aspirin and omeprazole in combination. OBJECTIVE: The aim of the present study was to develop and validate chromatographic method for simultaneous analysis of aspirin and omeprazole. METHODS: Isocratic, reversed phase stability indicating liquid chromatographic method was developed for the simultaneous determination of Aspirin and Omeprazole in combination. The separation was achieved on a Thermo Scientific Hypersil ODS (250 x 4.6 mm, 5 µm) column, kept at ambient temperature, using acetonitrile: methanol: 0.05 M phosphate buffer (40:5:55; pH 4 adjusted with 0.1% tri ethyl amine) as a mobile phase at a flow rate of 1 mL/min and UV detection was performed at 225 nm. RESULTS: The retention time was found to be 3.9 min for aspirin and 5.3 min for omeprazole. The method was observed to be linear in the range of 2 - 80 µg/mL for aspirin and 1 - 40 µg/mL for omeprazole, respectively. The proposed method was validated as per ICH guidelines Q2 (R1). The developed RP- HPLC method was successfully applied for the simultaneous estimation of aspirin and omeprazole in the presence of degradation products of both the drugs. CONCLUSION: The present study describes liquid chromatographic method for the estimation of aspirin and omeprzole in combination. The method can be used for the analysis of stability samples and routine quality control samples.

Possible anti-depressant effect of efavirenz and pro-depressive-like effect of voriconazole in specified doses in various experimental models of depression in mice.

BACKGROUND: Reports from experimental and clinical studies have indicated the possible relation between cholesterol and depression. Efavirenz (EFV) and Voriconazole (VRC) have been reported to affect cholesterol-24S-hydroxylase enzyme. The objective of the present study was to evaluate the effect of EFV and VRC in experimental models of depression in mice. METHODS: There was a measurement of immobility time in forced swim test and tail suspension test in which mice were previously subjected to the treatment of EFV (0.09mg/kg, orally (po)) and VRC (75mg/kg, intraperitoneally (ip)) separately for 14days. Sucrose intake was measured during stress schedule of 21days in chronic mild stress model in which mice were subjected to above mentioned drug treatment for last 14days. There was an estimation of serum total cholesterol and brain serotonin levels on day 21. RESULTS: The results indicated that mice treated with EFV showed a significant decrease in the immobility time and increase in sucrose intake with decrease in serum total cholesterol. Mice treated with VRC showed a significant increase in the immobility time and decrease in the sucrose intake with increase in serum total cholesterol. There was a significant increase and decrease in brain serotonin levels in mice treated with EFV and VRC respectively. CONCLUSION: The results of the present study indicates the possible anti-depressant effect of EFV and pro-depressive-like effect of VRC in specified doses in mice, raising the possibility that stimulation but not inhibition of cholesterol-24S-hydroxylase may be important in the treatment of depression.

Effects of piperine, cinnamic acid and gallic acid on rosuvastatin pharmacokinetics in rats.

The purpose of this study was to investigate the potential pharmacokinetic interactions with natural products (such as piperine (PIP), gallic acid (GA) and cinnamic acid (CA)) and rosuvastatin (RSV) (a specific breast cancer resistance protein, BCRP substrate) in rats. In Caco2 cells, the polarized transport of RSV was effectively inhibited by PIP, CA and GA at concentration of 50 µM. After per oral (p.o.) coadministration of PIP, CA and GA (10 mg/kg) significantly increased intravenous exposure (AUC(last)) of RSV (1 mg/kg) by 73.5%, 62.9% and 53.3% (p < 0.05), respectively than alone group (control). Compared with the control (alone) group, p.o. coadministration of PIP, CA and GA (10 mg/kg) significantly increased the oral exposure (AUC(last)) of RSV (5 mg/kg) by 2.0-fold, 1.83-fold (p < 0.05) and 2.34 -fold (p < 0.05), respectively. Moreover, the cumulative biliary excretion of RSV (5 mg/kg, p.o.) was significantly decreased by 53.3, 33.4 and 39.2% at the end of 8 h after p.o. co-administration of PIP, CA and GA (10 mg/kg), respectively. Taken together, these results indicate that the natural products such as PIP, CA and GA significantly inhibit RSV transport in to bile and increased the plasma exposure (AUC(last)) of RSV.

Split calibration curve: an approach to avoid repeat analysis of the samples exceeding ULOQ.

BACKGROUND: The current practice of using calibration curves with narrow concentration ranges during bioanalysis of new chemical entities has some limitations and is time consuming. In the present study we describe a split calibration curve approach, where sample dilution and repeat analysis can be avoided without compromising the quality and integrity of the data obtained. RESULTS: A split calibration curve approach is employed to determine the drug concentration in plasma samples with accuracy and precision over a wide dynamic range of approximately 0.6 to 15,000 ng/ml for dapsone and approximately 1 to 25,000 ng/ml for cyclophosphamide and glipizide. A wide dynamic range of concentrations for these three compounds was used in the current study to construct split calibration curves and was successfully validated for sample analysis in a single run. CONCLUSION: Using this method, repeat analysis of samples can be avoided. This is useful for the bioanalysis of toxicokinetic studies with wide dose ranges and studies where the sample volume is limited.

Formulation, evaluation and optimization of sustained release matrix tablets of captopril.

Sustained release matrix tablet is a delivery system by which the drug can be delivered at a controlled rate for long period of time. The present study aims at formulation, evaluation and optimization of captopril matrix tablets. A 3(2) full factorial design was adopted and all 9 batches were prepared by wet granulation method. Prepared granules and tablets were evaluated for precompression and postcompression characteristics respectively. Check point analysis was applied to the observations and the formula of the tablet was optimized. Optimized formula, F6 showed zero order drug release kinetics for the time period of 24 hours i.e. 17.55% release at the end of 2 hours, 53.4% release at the end of 12 hours and 100.24% release at the end of 24 hours. The results revealed that concentration of matrix forming agent and solution of granulating agent significantly affected in vitro drug release profile.