BIOEQUIVALENCE STUDIES OF MARKETED CLOZAPINE TABLETS BY USING OPTIMIZED VALIDATED LIQUID CHROMATOGRAPHIC METHOD

Objective: A simple, selective, precise and accurate method was developed for the estimation of Clozapine by RP-HPLC technique.Methods: Chromatographic conditions used are stationary phase, Phenomenex BDS (150 mm x 4.6 mm, 5µ), Mobile phase was methanol and water in (80:20) ratio and flow rate was maintained at 1.0 ml/min, column temperature was set at 25 °C, detection wavelength was 240 nm, and diluent was mobile phase. These conditions were finalized for the optimized method.Results: Linearity study was carried out between 10-60 µg/ml, the R2 value was found to be as 0.995. Precision was found to be as follows for system precision 1.052, method precision 1.662, and intraday precision 1.02 and for interday precision 0.93. The % Recovery was found to be 98.60%. LOD and LOQ were found to be 2.7 µg/ml and 8.4 µg/ml respectively. By using the above method assay of the marketed formulation was carried out and the % purity was found to be 99.28 %. Stability studies of Clozapine were done, in all conditions degradation was found to be within the acceptable range.Conclusion: The current validated method was finally applied in bioequivalence studies of four different brands of Clozapine by using dissolution apparatus and percentage drug release was found to be 99.48%, it was within the acceptable limit (NLT 85 %) as per USP

PROTEIN BINDING STUDY OF FELODIPINE USING VALIDATED LIQUID CHROMATOGRAPHIC METHOD

Objective: The aim of present study was to develop and validate a new simple, easy, selective, precise, accurate reverse phase high-performance liquid chromatography for the estimation of felodipine in bulk and pharmaceutical dosage form.Methods: The separation was carried on HPLC system consisting C18 column (150 mm ×4.6 nm, 5 µm) at room temperature coupled with a phenomenixcolumn silica with flow rate 1 ml/min. The mobile phase used was methanol: acetonitrile in the ratio of 50: 50. The drug was detected using UV-visible detector at the wavelength of 230 nm and run time was 10 min.Results: The retention time was 3.138 min. Linearity was observed in the concentration range of 5-25μg/ml. The accuracy of the method was assessed by percentage recovery studies at three different levels at 80%, 100% and 120% of its working concentration. The percentage recovery of felodipine in the developed method was found to be in the ranges of from 99.81-100.00% that indicates the good accuracy of the method. The percentage % RSD of precision was found to be less than 2%. The method was validated as per ICH guidelines. The developed method was employed in in vitro protein binding studies using semi permeable membrane and performed by plotting calibration curve (peak area vs concentration) the % drug release of felodipine was calculated.Conclusion: The proposed method was found to be simple, precise, accurate and consistent. The validated parameters are statistically validated for linearity, precision and limit of detection, limit of quantification, robustness, ruggedness were concluded.Â

REVIEW OF LANGALI (GLORIOSA SUPERBA LINN) – AGADA TANTRA PERSPECTIVE

Agadatantra is a branch of Ayurveda which deals with the symptoms and treatment of various animal, plant, artificial and latent poisons. The drug Langali (Gloriosa superb Linn) is being categorized under Moolavisha (poisonous roots) and is also one among the nine Upavishas (semi poisonous drugs) by different Ayurvedic pharmacopoeias. Even though it is poisonous it has got Shothahara (anti-inflammatory), Vranahara (wound healing), Krimigna (wormicidal), Shalyaharana (removal of foreign substances), Garbapaatana (abortificant) properties etc. It is being used by the Ayurvedic physicians in treatment of various ailments after proper purification. But its purificatory methods are not mentioned in Samhitas (treatises). It is mentioned in Ayurveda prakasha and traditional Agadatantra text books of Kerala. Here in this article an attempt is made to collect the information regarding Langali in Agadatantra perspective.The article includes both modern and Ayurvedic concepts in regards to its symptoms during poisoning and its treatment. Details regarding its purificatory methods and its therapeutic use in compound formulations as an antidote which has been mentioned in the traditional Agadatantra books which are available in Kerala have also been included

Concentration dependent diffusivities of model solvents in heavy oil

The rates of dissolution of heavy crude oil in liquid solvents and rates of desorption of solvents from oil have been measured. The crude oil used is a non-volatile heavy oil of 4253 mPa.s viscosity at room temperature. The solvents used are hexane, heptane and toluene. When the oil (black) is contacted with a solvent (transparent) an interface is seen which moves with time and takes a very long time to become fuzzy. The rate of movementof the front is measured. The dissolution experiments give very consistent results, but there are two parameters involved, Do, the diffusivity at infinite dilution and alpha which determines the concentration dependence. As a result it is necessary to do desorption experiments to be able to calculate both constants from the rate of movement of the front data. However, desorption experiments could not be performed under conditions of low concentrations suitable for the present case because of the very viscous nature of the oil. As a result, although the desorption experiments also showed good results, they could not be used to obtain good values of the parameters. When Stokes-Einstein equation was used to calculate Do, excellent results were obtained with alpha ~ 10 for the dissolution experiments and good deal smaller for the desorption experiments. That result is used to conclude that the above form for concentration dependent diffusivity is correct and concentration dependence is very high at low solvent concentrations explaining the sharp interfaces during dissolution.Other evidences have also been offered

Hexaaqua­zinc(II) dipicrate

In the title compound, [Zn(H2O)6](C6H2N3O7)2, the ZnII ion is located on an inversion center and is coordinated by six water mol­ecules in an octa­hedral geometry. The picrate anions have no coordination inter­actions with the ZnII atom. The three nitro groups are twisted away from the attached benzene ring by19.8 (3), 6.5 (4) and 28.6 (3)°. There are numerous O—H⋯O hydrogen bonds in the crystal structure

Environmental Reservoirs of Vibrio cholerae: Challenges and Opportunities for Ocean-Color Remote Sensing

The World Health Organization has estimated the burden of the on-going pandemic of cholera at 1.3 to 4 million cases per year worldwide in 2016, and a doubling of case-fatality-rate to 1.8% in 2016 from 0.8% in 2015. The disease cholera is caused by the bacterium Vibrio cholerae that can be found in environmental reservoirs, living either in free planktonic form or in association with host organisms, non-living particulate matter or in the sediment, and participating in various biogeochemical cycles. An increasing number of epidemiological studies are using land- and water-based remote-sensing observations for monitoring, surveillance, or risk mapping of Vibrio pathogens and cholera outbreaks. Although the Vibrio pathogens cannot be sensed directly by satellite sensors, remotely-sensed data can be used to infer their presence. Here, we review the use of ocean-color remote-sensing data, in conjunction with information on the ecology of the pathogen, to map its distribution and forecast risk of disease occurrence. Finally, we assess how satellite-based information on cholera may help support the Sustainable Development Goals and targets on Health (Goal 3), Water Quality (Goal 6), Climate (Goal 13), and Life Below Water (Goal 14)

Young elephants in a large herd maintain high levels of elephant endotheliotropic herpesvirus-specific antibodies and do not succumb to fatal haemorrhagic disease

Elephant endotheliotropic herpesviruses (EEHVs) have co-existed with elephants for millions of years, yet may cause fatal haemorrhagic disease (EEHV-HD), typically in elephants between 1 and 10 years of age. EEHV is omnipresent in (sub)adult elephants, and young elephants with low EEHV-specific antibody levels are at risk for EEHV-HD, suggesting that fatal disease may occur due to an insufficiently controlled primary infection. To further address this hypothesis, sera of three large elephant cohorts were subjected to a multiple EEHV species ELISA: (I) 96 Asian elephants between 0 and 57 years, including 13 EEHV-HD fatalities, from European zoo herds typically sized five to six elephants, (II) a herd of 64 orphaned elephants aged 0–15 years at the Elephant Transit Home in Sri Lanka and (III) 31 elephants aged 8–63 years, part of a large herd of 93 elephants at Pinnawala Elephant Orphanage, Sri Lanka. All Sri Lankan elephants showed high EEHV-specific antibody levels regardless of their age. While antibody levels of most European zoo elephants were comparable to those of Sri Lankan elephants, the average antibody level of the European juveniles (1–5 years of age) was significantly lower than those of age-matched Sri Lankan individuals. Moreover, the European juveniles showed a gradual decrease between 1 and 4 years of age, to be attributed to waning maternal antibodies. Maintenance of high levels of antibodies in spite of waning maternal antibodies in young Sri Lankan elephants is likely due to the larger herd size that increases the likelihood of contact with EEHV-shedding elephants. Together with the observation that low levels of EEHV-specific antibodies correlate with increased numbers of EEHV-HD fatalities, these results suggest that infection in presence of high maternal antibody levels may protect calves from developing EEHV-HD, while at the same time activating an immune response protective in future encounters with this virus

Young elephants in a large herd maintain high levels of elephant endotheliotropic herpesvirus-specific antibodies and do not succumb to fatal haemorrhagic disease

Elephant endotheliotropic herpesviruses (EEHVs) have co-existed with elephants for millions of years, yet may cause fatal haemorrhagic disease (EEHV-HD), typically in elephants between 1 and 10 years of age. EEHV is omnipresent in (sub)adult elephants, and young elephants with low EEHV-specific antibody levels are at risk for EEHV-HD, suggesting that fatal disease may occur due to an insufficiently controlled primary infection. To further address this hypothesis, sera of three large elephant cohorts were subjected to a multiple EEHV species ELISA: (I) 96 Asian elephants between 0 and 57 years, including 13 EEHV-HD fatalities, from European zoo herds typically sized five to six elephants, (II) a herd of 64 orphaned elephants aged 0–15 years at the Elephant Transit Home in Sri Lanka and (III) 31 elephants aged 8–63 years, part of a large herd of 93 elephants at Pinnawala Elephant Orphanage, Sri Lanka. All Sri Lankan elephants showed high EEHV-specific antibody levels regardless of their age. While antibody levels of most European zoo elephants were comparable to those of Sri Lankan elephants, the average antibody level of the European juveniles (1–5 years of age) was significantly lower than those of age-matched Sri Lankan individuals. Moreover, the European juveniles showed a gradual decrease between 1 and 4 years of age, to be attributed to waning maternal antibodies. Maintenance of high levels of antibodies in spite of waning maternal antibodies in young Sri Lankan elephants is likely due to the larger herd size that increases the likelihood of contact with EEHV-shedding elephants. Together with the observation that low levels of EEHV-specific antibodies correlate with increased numbers of EEHV-HD fatalities, these results suggest that infection in presence of high maternal antibody levels may protect calves from developing EEHV-HD, while at the same time activating an immune response protective in future encounters with this virus.http://wileyonlinelibrary.com/journal/tbedhj2022Veterinary Tropical Disease

Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production

BACKGROUND: As critical mediators of local and systemic inflammatory responses, cytokines are produced in the brain following ischaemic stroke. Some have been detected in the circulation of stroke patients, but their role and source is unclear. Focusing primarily on interleukin(IL)-1-related mechanisms, we serially measured plasma inflammatory markers, and the production of cytokines by whole blood, from 36 patients recruited within 12 h and followed up to 1 year after acute ischaemic stroke (AIS). RESULTS: Admission plasma IL-1 receptor antagonist (IL-1ra) concentration was elevated, relative to age-, sex-, and atherosclerosis-matched controls. IL-1β, soluble IL-1 receptor type II, tumour necrosis factor (TNF)-α, TNF-RII, IL-10 and leptin concentrations did not significantly differ from controls, but peak soluble TNF receptor type I (sTNF-RI) in the first week correlated strongly with computed tomography infarct volume at 5–7 days, mRS and BI at 3 and 12 months. Neopterin was raised in patients at 5–7 d, relative to controls, and in subjects with significant atherosclerosis. Spontaneous IL-1β, TNF-α and IL-6 gene and protein expression by blood cells was minimal, and induction of these cytokines by lipopolysaccharide (LPS) was significantly lower in patients than in controls during the first week. Minimum LPS-induced cytokine production correlated strongly with mRS and BI, and also with plasma cortisol. CONCLUSION: Absence of spontaneous whole blood gene activation or cytokine production suggests that peripheral blood cells are not the source of cytokines measured in plasma after AIS. Increased plasma IL-1ra within 12 h of AIS onset, the relationship between sTNF-RI and stroke severity, and suppressed cytokine induction suggests early activation of endogenous immunosuppressive mechanisms after AIS