RESUMEN

Correction for 'Identification, isolation, structural characterisation, synthesis and in silico toxicity prediction of the alkaline hydrolytic degradation product of brivaracetam by using LC-PDA, preparative HPLC, LC/HESI/LTQ, FTIR, and 1H NMR' by Pankaj Bhamare et al., Anal. Methods, 2020, 12, 1868-1881, https://doi.org/10.1039/C9AY02582K.

RESUMEN

Sulfasalazine needs frequent daily dosing and the administration of numerous tablets per day pose challenges to patient compliance, contributing to increased adverse effects and difficulties in disease control. These inconveniences result in less effective treatment for arthritis associated with inflammatory bowel disease i.e. ulcerative colitis etc. To improve drug bioavailability, a delayed-release mechanism that releases the drug at the colon is necessary. To develop and optimize colon-targeted controlled release bilayer tablets coated with pH-dependent polymers. The bilayer tablets containing the immediate release part and sustained release part were developed. The tablets were coated with enteric-coated with Eudragit® S-100 and l-100 to achieve release in the colon. Granule properties and tablets were evaluated. The physicochemical parameters of the tablets were evaluated including, stability study, and drug release in 0.1 N HCl (pH 1.2), pH 6.8 phosphate buffer, pH 7.4 phosphate buffer for 2, 1, and up to 24 h respectively. Radiographic imaging and in vivo pharmacokinetic studies were also done in Rabbits. The bilayer tablets containing immediate and sustained release were successfully developed for the colon targeting. The granule properties were found within the acceptable range indicating good flow properties. The physicochemical properties of the tablets were also found acceptable. The tablets did not show release in 0.1 N HCl and 6.8 phosphate buffer but drug release was found under control in the 7.4 pH buffer. Sulfasalazine coated bilayer tablets were found stable and no significant changes were observed in the stability studies. Based on the X-ray studies, the formulated tablet remained discernible in the stomach, small intestine, and colon for a duration of up to 24 h. Finally, by the 32nd hour, the tablet was no longer visible in the X-ray examination, leading to the conclusion of complete drug release. The drug concentration in plasma remained within the therapeutic range for up to 24 h in vivo. These novel formulations present substantial advantages, providing prolonged targeted drug release and reducing systemic adverse effects. The results suggest promising potential for treating arthritis in Inflammatory bowel disease (IBD) patients, offering a solution to current delivery systems.

Asunto(s)

Preparaciones de Acción Retardada , Liberación de Fármacos , Sulfasalazina , Sulfasalazina/farmacocinética , Sulfasalazina/administración & dosificación , Sulfasalazina/química , Animales , Conejos , Preparaciones de Acción Retardada/farmacocinética , Comprimidos , Artritis/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Disponibilidad Biológica , Comprimidos Recubiertos , Ácidos Polimetacrílicos/química , Masculino , Colon/metabolismo , Colon/efectos de los fármacos , Química Farmacéutica/métodos , Concentración de Iones de Hidrógeno , Antiinflamatorios no Esteroideos/farmacocinética , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/química , Composición de Medicamentos/métodos , Estabilidad de Medicamentos

RESUMEN

Collective cell migration (CCM), in which cell-cell integrity remains preserved during movement, plays an important role in the progression of cancer. However, studies describing CCM in cancer progression are majorly focused on the effects of extracellular tissue components on moving cell plasticity. The molecular and cellular mechanisms of CCM during cancer progression remain poorly explored. Here, we report that proteolipid protein 2 (PLP2), a colonic epithelium-enriched transmembrane protein, plays a vital role in the CCM of invasive human colorectal cancer (CRC) epithelium by modulating leading-edge cell dynamics in 2D. The extracellular pool of PLP2, secreted via exosomes, was also found to contribute to the event. During CCM, the protein was found to exist in association with ZO-1 (also known as TJP1) and to be involved in the positioning of the latter at the migrating edge. PLP2-mediated positioning of ZO-1 at the leading edge further alters actin cytoskeletal organization that involves Rac1 activation. Taken together, our findings demonstrate that PLP2, via its association with ZO-1, drives CCM in CRC epithelium by modulating the leading-edge actin cytoskeleton, thereby opening up new avenues of cancer research. This article has an associated First Person interview with the first author of the paper.

Asunto(s)

Neoplasias Colorrectales , Exosomas , Movimiento Celular , Neoplasias Colorrectales/genética , Citoesqueleto , Humanos , Proteínas con Dominio MARVEL , Proteínas de la Membrana/genética , Proteolípidos

RESUMEN

Purpose: The prevalent types of idiopathic inflammatory bowel disease are ulcerative colitis (UC) and Crohn's disease, which affects a large number of populations. Budesonide (BUD) is a glucocorticoid with potent anti-inflammatory activity but low systemic efficacy because of high receptor affinity and rapid diversion. To overcome low efficacy and availability, a novel BUD nano-sponges was formulated using quasi- solvent diffusion and Eudragit S-100 as polymer. It was then investigated for the effect of process variables using Box-Behnken design. Methods: The BUD Nano sponges were evaluated for particle size, particle size, polydispersity, percent drug entrapment, drug release pattern. The formulation was evaluated by an in vivo study using male Wistar rats and parameters such as clinical activity score, colon/body weight ratio (C/B ratio), macroscopic ulceration (damage score) activity were performed. Finally, histopathological examination was performed on colon tissue samples. Results: The formulation showed better efficacy and availability as compared with the available formulations of BUD, which indicates the good efficacy of the formulated nanosponges. The clinical activity score was attenuated by the formulated nanosponges in the Wistar rats. The colon to body weight ratio was significantly reduced as compared with the control formulation. The histopathology of colon treated with nanosponges showed normal structure and architecture of the colon. Conclusion: The results of the present work confirmed the utility of BUD nano-sponges as novel carriers in management IBD.

RESUMEN

BACKGROUND: The medicinal plants have enormous pharmacological properties with fewer side effects. Today, there is an increasing demand of medicinal plants as an anti-aging and anti-wrinkle agent. ; Objective: The aim of this study is to evaluate the antioxidant, anti-aging and anti-wrinkle potential of Salvia officinalis. ; Materials and Methods: Salvia officinalis (Lamiaceae) is folk medicine of Asia and Latin America. Powdered crude drug 100 g was successively extracted in a soxhlet apparatus with petroleum ether (60-80ºC), chloroform and methanol. After successive solvents, extraction methanolic extract was used for testing of antioxidant potential using DPPH assay. Further, the antiaging potential of the extract was investigated by the inhibitory effect of various enzymatic estimations i.e. Col-I, Ela- I and Hya-I inhibitory assays on early aging human skin fibroblasts. The antiwrinkle potential of plant Salvia officinalis was done by using a UV light-induced photoaging model. ; Results: Phytochemical analysis showed the presence of glycosides, alkaloids flavonoids, and triterpenoids, saponins and Phenolic Compounds at high level. The extract showed inhibitory concentration (IC50: 24.65) and ascorbic acid. The standard antioxidant showed inhibitory concentration (IC50: 20.10). In enzymatic estimations assay, the Col-I, Ela-I and Hya-I of extract were assessed showing inhibitory concentration as Col-I (IC50:21.36), Ela-I (IC50:35.05) and Hya-I (IC50:23.44), respectively. Thus, MeOH extract of Salvia officinalis can inhibit 50% of the activity of aging-related enzymes Col-I, Ela-I and Hya-I. The wrinkle score of negative control i.e. UV treated group was 2.83 ± 0.408, and MeOH extract of Salvia officinalis treated group is 1.83 ± 0.753. ; Conclusion: This study concluded that MeOH extract of Salvia officinalis has confirmed the high antioxidant potential and in vitro and in vivo inhibitory potential of antiaging enzymes assessed, thus they could be used for further development of cosmetic products and nutraceuticals.

Asunto(s)

Salvia officinalis , Envejecimiento de la Piel , Antioxidantes/farmacología , Humanos , Metanol , Extractos Vegetales/farmacología , Rayos Ultravioleta/efectos adversos

RESUMEN

BACKGROUND: Woodfordia fructicosa is used traditionally for the treatment of inflammation associated with arthritis. METHODS: In the present study, the anti-inflammatory activity of W. fructicosa (WFE) leaves ethanolic extract was assessed in Sprague Dawley rats by giving 200 mg/kg dose orally. Inflammation was studied by using carrageenan induced paw edema, Freund's adjuvant (FA) and monosodium iodo acetate (MIA) induced arthritis as animal models. Serum tumor necrosis factor-alpha (TNF-α) was estimated in blood sample of animals treated with FA. The one way ANOVA followed by Bonferroni's test was used for statistical analysis. RESULTS: WFE significantly decreased (P<0.05, P<0.001) paw thickness in carrageenan induced paw edema and FA induced arthritis. The significant decrease in knee diameter (P<0.001) in MIA induced arthritis as well as inhibitory effect (P<0.001) on elevated TNF- α was observed. CONCLUSION: These results showed that the WFEexerted an inhibitory effect on TNF-α and carrageenan paw edema which may justify its traditional use in inflammatory conditions. Thus, the study shows that leaves of W. fruticose afford anti-inflammatory activity by preventing the inflammation in different animal models.

Asunto(s)

Antiinflamatorios/uso terapéutico , Artritis Experimental/terapia , Extractos Vegetales/uso terapéutico , Animales , Artritis Experimental/inducido químicamente , Carragenina , Etanol , Femenino , Adyuvante de Freund , Humanos , Masculino , Hojas de la Planta , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo , Woodfordia/inmunología

RESUMEN

Brivaracetam is a racetam derivative of levetiracetam with very limited data available on its degradation behaviour. An official HPLC method for brivaracetam has not been published yet to resolve the degradation products generated during stability studies. Therefore, an isocratic reverse phase HPLC-UV method was developed for the determination of brivaracetam in the presence of its related impurities and degradation products. Efficient chromatographic separation was achieved on an Inertsil ODS 3 V, 150 mm × 4.6 mm, 5 µ column with the mobile phase containing a mixture of 0.1% v/v trifluoroacetic acid solution and acetonitrile (60 : 40 v/v) at a flow rate of 1.0 ml min-1 with the eluent monitored at 210 nm. The proposed method was validated as per the ICH Q2 (R1) guidelines. The method was validated for specificity, linearity, precision, accuracy and robustness. For the assay, the calibration plot was linear over the concentration range of 141 µg ml-1 to 262 µg ml-1 of brivaracetam with a correlation coefficient (r2) of 0.99981. For the study of related substances, the calibration plot was linear over the concentration range of 0.0147 µg ml-1 to 2.93 µg ml-1 of brivaracetam with a correlation coefficient (r2) of 0.99994 and 0.0148 µg ml-1 to 2.96 µg ml-1 of the base degradation product of brivaracetam with a correlation coefficient (r2) of 0.99994. The proposed method was used to investigate the degradation kinetics of brivaracetam under different stress conditions. The drug was found to be less stable under basic degradation conditions. The method shows consistent recoveries for brivaracetam (100.22% at the 70% level, 100.02% at the 100% level and 99.14% at the 130% level of the test concentration i.e. 200 µg ml-1 of brivaracetam). The method was found to be accurate, precise, linear, specific, sensitive, rugged, robust, and useful for characterizing the stability of the drug molecule. The marketed formulation (brand name: Briviact) was analysed by using the proposed method; we have carried out identification, isolation, structural characterisation and in silico toxicity prediction of the alkaline hydrolytic degradation product of brivaracetam by using LC-PDA, preparative HPLC, LC/HESI/LTQ, FTIR and 1H NMR. The predicted alkaline degradation product was found to be 2-(4-methyl-2-oxo-1-pyrrolidinyl) butyric acid (i.e. a brivaracetam acid impurity generated after alkaline hydrolysis of brivaracetam). In silico toxicity prediction was carried out by using the eMolTox webserver. The synthesis of isolated impurities of brivaracetam has also been carried out successfully.

RESUMEN

Microemulsions are thermodynamically stable, transparent, colloidal drug carrier system extensively used by the scientists for effective drug delivery across the skin. It is a spontaneous isotropic mixture of lipophilic and hydrophilic substances stabilized by suitable surfactant and co-surfactant. The easy fabrication, long-term stability, enhanced solubilization, biocompatibility, skin-friendly appearance and affinity for both the hydrophilic and lipophilic drug substances make it superior for skin drug delivery over the other carrier systems. The topical administration of most of the active compounds is impaired by limited skin permeability due to the presence of skin barriers. In this sequence, the microemulsion represents a cost-effective and convenient drug carrier system which successfully delivers the drug to and across the skin. In the present review work, we compiled various attempts made in last 20 years, utilizing the microemulsion for dermal and transdermal delivery of various drugs. The review emphasizes the potency of microemulsion for topical and transdermal drug delivery and its effect on drug permeability.

Asunto(s)

Portadores de Fármacos/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Emulsiones/metabolismo , Microesferas , Absorción Cutánea/fisiología , Administración Cutánea , Administración Tópica , Animales , Portadores de Fármacos/administración & dosificación , Emulsiones/administración & dosificación , Humanos , Absorción Cutánea/efectos de los fármacos

RESUMEN

The Jan Aushadhi Scheme (JAS) initiated by the Government of India is a powerful intervention against the unjustifiable pricing of medicines by private pharmaceutical industry, to make the generic medicines available at affordable prices. The marginalized populations of India are not able to afford many branded medicines; hence, there is an urgent need for making the cheaper generics available to Indians in the best interest of populations. It has been observed that lack of awareness in the public, distribution of free medicines by state governments, lack of support for JAS, poor supply chain, and doctors not prescribing generic medicines are the major constraints faced by the JAS leading to its poor success.

RESUMEN

Purpose: Desmopressin acetate (DDAPV), a synthetic analogue of vasopressin, has been recommended to be used in diabetes insipidus, mild forms of hemophilia and Von Willebrand disease. The DDAPV is available for adminstration via different routes viz. oral, parenteral and nasal, however its dose is very less in case of nasal sprays (20 µg) and parenteral route (4 µg) compared to oral route (0.1 to 0.3 mg in tablet). A sensitive and selective method is needed to be developed and validated for assay of low concentrations of DDAPV in its pharmaceutical dosage form i.e. nasal spray. Methods: Simple and specific HPLC-Fluorescecne method has been proposed for the quantitation of DDAPV at nanogram level in nasal formulations for the first time. DAPV, DDAPV EP impurity-B, chlorobutanol, benzalkonoium chloride were successfully derivatised with Ortho-Phthalaldehyde (OPA) and co-eluted on a C8 (50×2.1 mm, 3.5 µm particle size, 120Å) with mobile phase composed of 0.1% trifluroacetic acid, acetonitrile and Isopropyl alcohol in ratio of 70:25:5. The emission was measured at 450nm and flow rate was 0.8ml/min. The reaction was optimized in the terms of pH, stability of formed fluorophore and time consumed during the reaction. Results: The maximal fluorescence intensity was reached when the solutions were mixed for 3 min, and remained constant for at least 30 min at 20-25ºC. The calibration curve was found linear from 50 to 5000 ng/ml with weight of 1/X2. The limit of detection was 10ng/ml and precision was less than 2.0. Conclusion: The developed HPLC-fluorescence assay method was successfully applied for quantitation of DDAPV in nasal spray. HPLC-Fluorescence method was specific, sensitive, precise and accurate for determination of DDAPV. The method was able to quantify DDAPV at 50ng/ml with sufficient accuracy and precision. The validated HPLC-Fluorescence was successfully applied.

RESUMEN

INTORODUCTION: Prodrug approach deals with chemical biotransformation or enzymatic conversion or involves inactive or less active bio-reversible derivatives of active drug molecules. They have to pass through enzymatic or chemical biotransformation before eliciting their pharmacological action. METHODS & MATERIALS: The two different pharmacophores combine to give synergistic activity or may help in targeting the active drug to its target. Prodrug super seeds the problems of prodrug designing, for example solubility enhancement, bioavailability enhancement, chemical stability improvement, presystemic metabolism, site specific delivery, toxicity masking, improving patient acceptance, or eradicating undesirable adverse effects. RESULTS: As an outcome the search for a prodrug or mutual prodrug with reduced toxicity has continued during recent years. This present review emphasizes the common help to revamp physiochemical, pharmaceutical and therapeutic effectiveness of drugs. CONCLUSION: This gives the researcher a common platform where they can find prodrugs of commonly used NSAIDs to overcome the gastrointestinal toxicity (irritation, ulcergenocity and bleeding).

RESUMEN

A series of 1-(substituted-phenyl)-1-[(2-chloroquinolin-3-yl)methyl]thiocarbamide and 1-(substituted-phenyl)-1-[(2-chloroquinolin-3-yl)methyl]methylthiocarbamide derivatives was synthesized as antitubercular agent. The structure of quinolinyl amines and their thiocarbamide derivatives were established on the basis of IR, (1)H and (13)C-NMR and mass spectral data. All the compounds were tested in vitro for antimycobacterial activity against Mycobacterium tuberculosis (ATCC-25177) in Lowenstein-Jensen medium by well diffusion method and MIC by twofold serial dilution method. Results of the antitubercular screening revealed that compounds showed moderate to good antitubercular activity. Compound having two halogens in the phenyl rings viz. 3g, 3h, 4g, and 4h exhibited MIC of 50 µg/mL. The computational parameters relevant to absorption and permeation of target compounds were also calculated and found to be well correlated with antitubercular activity.

Asunto(s)

Antituberculosos/química , Antituberculosos/farmacología , Evaluación Preclínica de Medicamentos/métodos , Administración Oral , Antituberculosos/síntesis química , Antituberculosos/farmacocinética , Disponibilidad Biológica , Técnicas de Química Sintética , Cloroquinolinoles/química , Etionamida/farmacología , Humanos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Mycobacterium tuberculosis/efectos de los fármacos , Relación Estructura-Actividad , Tiourea/química

RESUMEN

Bacopa monnieri, Evolvulus alsinoides and Tinospora cordifolia are established ayurvedic herbs having neuropharmacological effect. In present study is aimed to Phytochemical Comparison between Pet ether and Ethanolic extracts of Bacopa monnieri (BME), Evolvulus alsinoides (EAE) and Tinospora cordifolia (TCE). To identify the presence (+) or absence (-) of different phytoconstituents in Pet ether and Ethanolic extracts of BME, EAE and TCE by using various phytochemical testing methods. Phytochemical investigation showed the presence of various phytochemical constituents in Pet ether and Ethanolic extracts of BME, EAE and TCE. When comparison between Pet ether and Ethanolic extracts of BME, EAE and TCE; Ethanolic extracts of these plants showed more phytoconstituents as compared to Pet ether extracts of these plants. From present investigation, it can be concluded that phytochemical comparison is subsequently momentous and useful in finding chemical constituents in the plant substances that may lead to their quantitative evaluation and also pharmacologically active chemical compounds.

Asunto(s)

Alcanos/química , Bacopa/química , Convolvulaceae/química , Etanol/química , Extractos Vegetales/análisis , Solventes/química , Tinospora/química , Medicina Ayurvédica , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales

RESUMEN

Acitretin is a photosensitive oral retinoid with very limited data available on its degradation. The official HPLC method for acitretin determination was insufficient to resolve the degradation products generated during stability studies. Therefore, an isocratic RP-HPLC-UV method was developed for the determination of acitretin in the presence of its related impurities and degradation products. Efficient chromatographic separation was achieved on a Thermo beta-basic column C18 (100 mm×4.6 mm, 5 µm) with mobile phase containing 0.3% (v/v) glacial acetic acid with acetonitrile (ACN) and isopropyl alcohol (IPA) in an isocratic ratio of 70:30 at a flow rate of 1.0 mL/min with the eluent monitored at 360 nm. The method was validated for specificity, linearity, precision, accuracy and robustness. The calibration plot was linear over the concentration range of 50-150 µg/mL with a correlation coefficient (r (2)) of 0.999. The proposed method was used to investigate the degradation kinetics of acitretin under the different degradative conditions. The degradation rate constant (K), half-life (t 1/2), and t 90 were calculated. Degradation of acitretin followed pseudo-first-order kinetics. The drug was found to be less stable under acidic and photolytic degradation conditions: the photolytic degradation constants for acitretin in sunlight and UV light were 0.002698% and 0.0008402% min(-1), respectively. The LOD for acitretin and the known impurities were at a level below 0.02%. The method shows consistent recoveries for ACTR (99.8%-101.2%) and also for its known impurities (97.2-101.3%). The method was found to be accurate, precise, linear, specific, sensitive, rugged, robust, and useful for characterizing the stability of this chemical.

RESUMEN

OBJECTIVE: To research the acute toxicity of Illicium verum (I. verum) fruit extracts and its action on central nervous system. METHODS: The TLC and HPTLC techniques were used as fingerprints to determine the chemical components present in I. verum. Male albino rats and mice were utilized for study. The powdered material was successively extracted with n-hexane, ethyl acetate and methanol using a Soxhlet extractor. Acute toxicity studies were performed as per OECD guidelines. The CNS activity was evaluated on parameters of general behavior, sleeping pattern, locomotor activity, anxiety and myocoordination activity. The animals were trained for seven days prior to experiments and the divided into five groups with six animals in each. The drug was administered by intraperitoneal route according to body weight. The dosing was done as prescribed in each protocol. RESULTS: Toxicity studies reported 2 000 mg/kg as toxicological dose and 1/10 of the same dose was taken as therapeutic dose Intraperitoneal injection of all extracts at dose of 200 mg prolonged phenobarbitone induced sleeping time, produced alteration in general behavior pattern, reduced locomotor activity and produced anxiolytic effects but the extracts do not significantly alter muscles coordination activity. The three extracts of I. verum at the dose of 200 mg, methanol extract was found to produce more prominent effects, then hexane and ethylacetate extracts. CONCLUSIONS: The observation suggested that the extracts of I. verum possess potent CNS depressant action and anxiolytic effect without interfering with motor coordination.

Asunto(s)

Ansiolíticos/farmacología , Ansiedad/tratamiento farmacológico , Depresores del Sistema Nervioso Central/farmacología , Sistema Nervioso Central/efectos de los fármacos , Illicium , Medicina Tradicional China , Preparaciones de Plantas/farmacología , Animales , Ansiolíticos/administración & dosificación , Ansiolíticos/efectos adversos , Ansiedad/patología , Sistema Nervioso Central/patología , Depresores del Sistema Nervioso Central/administración & dosificación , Depresores del Sistema Nervioso Central/efectos adversos , Cromatografía Liquida/métodos , Relación Dosis-Respuesta a Droga , Frutas , Illicium/química , Inyecciones Intraperitoneales , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Fitoterapia/métodos , Preparaciones de Plantas/administración & dosificación , Preparaciones de Plantas/efectos adversos , Ratas , Sueño/efectos de los fármacos , Solventes

RESUMEN

The effects of ethanolic extracts of whole plants of Bacopa monnieri (BME), Evolvulus alsinoides (EAE), Tinospora cordifolia (TCE) and their combinations in equal proportion [CEP-1 (BME+EAE), CEP-2 (BME+TCE), CEP-3 (EAE+TCE) and CEP-4 (BME+EAE+TCE)] were tested in amnesic rats using Radial arm maze task performance (RAM) and Barnes maze test at 200 mg/kg p.o. The latency to find food and target hole was observed in RAM and Barnes maze respectively. Cognitive dysfunction was induced by scopolamine (0.3 mg/kg i.p.) treatment. BME, EAE, TCE and their combinations of equal proportion (CEPs) showed significant decrease in latency to find food and target hole in RAM and Barnes maze respectively. Inter comparison among single extract alone treated groups revealed that BME treated animals showed significant difference as compared to EAE and TCE treated animals. All combinations of equal proportion (CEPs) of these extracts showed significant difference in latency to find food and target hole as compared to single extracts treated animals. CEP-1 showed significantly better effect as compared to CEP-2 and CEP-3. Significant difference in latency to find food and target hole was also present between CEP-2 and CEP-3. Effect of CEP-4 was found to be significantly better than CEP-1, CEP-2 and CEP-3 treated rats in both models. From present investigation, it was concluded that ethanolic extract of Bacopa monnieri, Evolvulus alsinoides and Tinospora cordifolia provided better nootropic effect when used in combination.

Asunto(s)

Bacopa , Conducta Animal/efectos de los fármacos , Cognición/efectos de los fármacos , Convolvulaceae , Etanol/química , Nootrópicos/farmacología , Extractos Vegetales/farmacología , Solventes/química , Tinospora , Animales , Femenino , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Nootrópicos/química , Fitoterapia , Extractos Vegetales/química , Plantas Medicinales , Ratas , Ratas Wistar , Tiempo de Reacción , Factores de Tiempo

RESUMEN

OBJECTIVE: To study the influence of methanolic and aqueous extract of Withania somnifera (W. somnifera) root on the marble-burying behavior of mice a well-accepted model of obsessive compulsive behavior. METHODS: Mice were divided in different groups (n = 6). Fluoxetine (5, 10, 15 mg/kg), (10, 25, 50, 100 mg/kg) and methanolic extract W. somnifera (MEWS) (10, 25, 50, 100 mg/kg) were administered i.p. 30 min. prior to the assessment of marble burying behavior and locomotor activity. The control group received vehicle of the extract. RESULTS: Administration of aqueous extracts W. somnifera (AEWS) and MEWS (50 mg/kg) successively decreased the marble burying behavior activity without affecting motor activity. This effect of AEWS and MEWS was comparable to standard fluoxetine, ritanserin and parachlorophenylalanine. CONCLUSIONS: W. somnifera extract is effective in treating obsessive compulsive disorder.

Asunto(s)

Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Fitoterapia/métodos , Extractos Vegetales/farmacología , Withania , Análisis de Varianza , Animales , Ansiolíticos/farmacología , Femenino , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Raíces de Plantas , Ritanserina/farmacología

RESUMEN

A stability-indicating liquid chromatographic method has been developed and validated for the determination of Diltiazem Hydrochloride (DTZ) together with its six related substances (Diltiazem sulphoxide, Imp-A, Imp-B, Imp-D, Imp-E, and Imp-F) in a laboratory mixture as well as in a novel tablet formulation developed in-house. Efficient chromatographic separation was achieved on a Hypersil BDS C18 (150 mm×4.6 mm, 5.0 µm) with mobile phase containing 0.2% Triethylamine (TEA) in gradient combination with acetonitrile (ACN) at a flow rate of 1.0 mL/min and the eluent was monitored at 240 nm. In the developed method, the resolution of DTZ from any pair of impurities was found to be greater than 2.0. The test solution and related substances were found to be stable in the diluent for 24 h. The developed method resolved the drug from its known impurities, stated above, and also from additional impurities generated when the formulation was subjected to forced degradation; the mass balance was found close to 99.9%. Regression analyses indicate correlation coefficient value greater than 0.997 for DTZ and its six known impurities. The LOD for DTZ and the known impurities was at a level below 0.02%. The method has shown good, consistent recoveries for DTZ (99.8-101.2%) and also for its six known impurities (97.2-101.3%). The method was found to be accurate, precise, linear, specific, sensitive, rugged, robust, and stability-indicating.

RESUMEN

A stability-indicating liquid chromatographic method has been developed and validated for the determination of Diltiazem Hydrochloride (DTZ) together with its six related substances (Diltiazem sulphoxide,Imp-A,Imp-B,Imp-D,Imp-E,and Imp-F) in a laboratory mixture as well as in a novel tablet formulation developed in-house.Efficient chromatographic separation was achieved on a Hypersil BDS C18 (150mm ×4.6mm,5.0μm) with mobile phase containing 0.2％ Triethylamine (TEA) in gradient combination with acetonitrile (ACN) at a flow rate of 1.0 mL/min and the eluent was monitored at 240 nm.In the developed method,the resolution of DTZ from any pair of impurities was found to be greater than 2.0.The test solution and related substances were found to be stable in the diluent for 24 h.The developed method resolved the drug from its known impurities,stated above,and also from additional impurities generated when the formulation was subjected to forced degradation; the mass balance was found close to 99.9％.Regression analyses indicate correlation coefficient value greater than 0.997 for DTZ and its six known impurities.The LOD for DTZ and the known impurities was at a level below 0.02％.The method has shown good,consistent recoveries for DTZ (99.8-101.2％) and also for its six known impurities (97.2-101.3％).The method was found to be accurate,precise,linear,specific,sensitive,rugged,robust,and stability-indicating.

RESUMEN

INTRODUCTION: 1,2,4-triazoles and its derivatives have been reported to possess anti-inflammatory, analgesic, antimicrobial, anticancer, antitumor, antitubercular, anticonvulsant, openers of Ca-activated potassium (Maxi-K) channels, antiviral properties, hypoglycemic, anxiolytic and antidepressant activity. Therefore, 1,2,4-triazole seems to be an important pharmacophore. MATERIALS AND METHODS: The synthesis of 4-(substituted ethanoyl) amino-3-mercapto-5-(4-methoxy) phenyl-1,2,4-triazoles (6a-o) were prepared following six step starting 4-methoxy benzoic acid and using different secondary amines and were characterized with the help of FT-IR,(1)H,(13)C NMR, FAB Mass and nitrogen analysis. These synthesized compounds (6a-o) were then evaluated for anti-inflammatory activity by carrageenan induced paw edema method.Out of these synthesized compounds, some (6f, i and k) were evaluated for antinociceptive activity by Hot plate method and Tail immersion method. RESULTS AND DISCUSSION: The synthesis of 4-(substituted amino)-3-mercapto-5-(4-methoxy) phenyl-1,2,4-triazoles (6a-o) was accomplished. The IR spectra exhibited characteristic bands for C-N, C=N, SH and C=O at 1350-1360, 1511-1548, 2520-2594.3 and 1650-1719 cm(-1). The C-O-C asymmetric and symmetric str. was at 1250-1254 and 1027-1079.3 cm(-1) respectively. In(1)H-NMR spectra, a singlet of CONH was found in the range of δ 9.92-10.18 ppm and another singlet of thiol group was observed in the range of δ 8.63-9.92 ppm. A singlet of Ar-OCH(3) was also found between δ 3.57-3.91 ppm. In(13) C- NMR spectra, C-3 and C-5 of the 1,2,4 - triazole nucleus were observed in the range of δ 147-166.9 ppm. Carbonyl carbon and methylene carbon of -NHCOCH(2) N< were found between δ 166.5-177.5 and δ 47.1-62 ppm respectively. Acute toxicity study was donr following OECD-423 and cut-off dose was found to be between 1000-1500 mg/kg body weight. At the dose level of 100 mg/kg, 6f, 6i and 6k exhibited appreciable inhibition of oedema especially 6k exhibiting a percentage of oedema inhibition of 40.28%, which was comparable to that of the standard drug indomethacin (62.50% at 10mg/kg dose). Among the compounds tested, compound 6k exhibited good anti-nociceptive activity in both methods used. Pethidine (20mg/kg body weight s.c) is used as the standard drug. CONCLUSION: SAR of these synthesized compounds shows that substitution with heterocyclic moiety at C-2 of the acetamido group at position 4 of the 1,2,4-triazole produces appreciable activity as compared to substitution with aliphatic moieties since among all the synthesized compounds, the most active ones are 6f, 6i and 6k that have piperdine, 1-benzyl piperazine and morpholine group, respectively at C-2 of the acetamido group at position 4 of the 1,2,4-triazole.