ABSTRACT

The aim of the present study was to develop Controlled release formulation of Cefpodoxime proxetil and to optimize the suitable polymer to maintain constant therapeutic levels of the drug for over 12 hrs. Methocel E5, PEG6000, and HEC, Methocel K100LV were employed as polymers. Cefpodoxime proxetil dose was fixed as 200 mg. Polymers were used in the concentration of 100, 150 and 200 mg. All the formulations were passed various physicochemical evaluation parameters and they were found to be within limits, whereas from the dissolution studies it was evident that the formulation (F11) showed better and desired drug release pattern i.e., 90.73 %. It contains Methocel K100LV as controlled release material. It followed zero order release kinetics mechanism.

Keywords: Cefpodoxime proxetil, Methocel E5, PEG6000, HEC, Methocel K100LV and Controlled release tablets.

ABSTRACT

Genistein (GE) has been shown to suppress the growth of various cancers through modulation of various pathways , in particular, reactivation of estrogen receptor alpha ( ERα). This compound significantly decreases methylation of DNA promoter by reduction of DNMT1 activity . Tamoxifen( TAM) alters steroid binding domain which prevents gene activation and affects the tumor growth . GE and TAM have significant anti-tumor effects .The aim of the present study was to analyse the effects of GE on ERα and DNMT1 expression and also apoptotic and antiprolifrative effects of GE and TAM on hepatocellular carcinoma . The cells were incubated with certain concentrations of GE (1, 5, 10, 25, 50, 75, and 100 μM) and the same concentrations of TAM and MTT assay were performed to assess cells viability. Apoptotic effects of these compounds with 25 μM concentration (alone and combined) were measured by using flow cytometry at different times (24, 48 and 72 h).The expression level of ERα and DNMT1 were determined by quantitative real-time RT PCR. our result demonstrated that , GE increases ERα and decreases DNMT1 gene expression , GE and TAM inhibit cell viability and induce apoptosis significantly . The cell viability was decreased and the apoptotic cells were increased significantly but combined compound induced apoptosis more significantly. The relative expression of ERα in GE (25 μM) treatment group were increased and that of DNMT1 were decreased significantly. According to our results, GE can epigenetically increase ERα expression by inhibition of DNMT1 expression which in turn increases apoptotic effect of tamoxifen. Furthermore, combination of GE and TAM induce apoptosis more significantly and also GE and TAM inhibit proliferation significantly in a dose- and time-dependent manner.

Keywords: GE, TAM , ERα, DNMT1, Epigenetic, Hepatocellular carcinoma.

ABSTRACTWe have synthesized a new series of 5-(substituted benzylidene)-3-[(substituted)-methyl]-1,3-thiazolidine-2,4-dionederivative and the structures of the new compounds were confirmed by physical parameters like solubility, melting point,chromatographic methods (TLC) and at last spectroscopic methods (IR, 1H NMR).The thiozolidinediones are improving insulinsensitivity and lowering blood glucose, free fatty acid, and triglyceride levels. The thiozolidinediones are PPARγ(peroxisomeproliferator-activated receptor) agonist. Since our titled compounds are known to possess anti-diabetic activity. Theantidiabetic activity of the synthesized compounds has been carried out by male Wister rats weighing between 80-150 gm usingglibenclamide as standard drug. Apart from this it has also been reported that derivatives of 1,3-thiazolidine-2,4-dionecondensed nucleus systems exert diverse pharmacological activities such as antimicrobial anti-inflammatory, anticancer,antidiabetic etc.Keywords: Antidiabatic activity, 1,3-thiazolidine-2,4-dione, glibenclamide.

ABSTRACTCarum carvi was used traditionally in different populations for many medical complains. It contained a wide range ofchemical constituents. Essential and volatile oils, flavonoids, proteins, carbohydrate and many vitamins and trace elements. Theprevious studies showed that the seeds of the plant and its constituents exerted antimicrobial, anticancer, antioxidant,hypolipidemic, antidiabetic, analgesic, diuretic, gastrointestinal, bronchial relaxant effects and many other pharmacologicalactivities. This paper is a step ahead to open a new insight for the therapeutic efficacy of Carum carvi.

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ABSTRACT The objective of this study is to formulate and evaluate sustained release tablets of Pioglitazone HCl, which were developed to prolong the action leading to an increase in drug bioavailability and reduced dosing frequency. Sustained release (SR) drug delivery systems are developed to modulate the release of drug, in order to achieve specific clinical objectives that cannot be attained with conventional dosage forms. Possible therapeutic benefits of a properly designed SR dosage form include low cost, simple processing, improved efficacy, reduced adverse events and flexibility in terms of the range of release profiles attainable. Two different grades of HPMC K 100M, HPMC K15M and PEO, carbopol, Xanthum gum, MCC, Magnesium stearate and talc were used as variants along with pioglitazone HCl as active pharmaceutical ingredient. All these polymers are used in different concentrations to sustain the action. The tablets were prepared by direct compression method and are evaluated for pre compressional studies like bulk density, tapped density, compressibility index, Hausner ratio and angle of repose; all the values were found within limits of standard. In vitro release studies were carried out by USP type II paddle apparatus. The interaction of polymer and drug ruled out by FTIR studies. The FTIR studies confirmed that there is no interaction between the drug and polymer. Data of in-vitro release of tablets were fit in different equations and kinetic models to explain release kinetics the models used were zero order and first order equations. Higuchi and Korsmeyer peppas models based on physiochemical properties and in vitro release studies. The results showed that HPMC K15M produce sustained release of drug. The formulation F10 (HPMCK15M) with 1:3 ratio produced 99% drug release at 12 h. Key words: Sustained release dosage form, HPMC K100M, HPMC K15M, PEO, Carbopol, Xanthan gum, Release kinetics

ABSTRACTCapparis spinosa contained many biologically active chemical groups including, alkaloids, glycosides, tannins,phenolics, flavonoids, triterpenoids steroids, carbohydrates, saponins and a wide range of minerals and trace elements. Itexerted many pharmacological effects including antimicrobial, cytotoxic, antidiabetic, anti-inflammatory, antioxidant,cardiovascular, bronchorelaxant and many other effects. The present review will designed to highlight the chemical constituentsand the pharmacological effects of Capparis spinosa.Keywords: Capparis spinosa, pharmacology, constituents.

ABSTRACT Alzheimer’s disease is the most common cause of dementia in elderly people. Research into Alzheimer’s disease therapy has been at least partly successful in terms of developing symptomatic treatments, but has also had several failures in terms of developing disease-modifying therapies. These successes and failures have led to debate about the potential deficiencies in our understanding of the pathogenesis of Alzheimer’s disease and potential pitfalls in diagnosis, choice of therapeutic targets, development of drug candidates, and design of clinical trials. Many clinical and experimental studies are ongoing, but we need to acknowledge that a single cure for Alzheimer’s disease is unlikely to be found and that the approach to drug development for this disorder needs to be reconsidered. Preclinical research is constantly providing us with new information on pieces of the complex Alzheimer’s disease puzzle, and an analysis of this information might reveal patterns of pharmacological interactions instead of single potential drug targets. Several promising randomized controlled trials are ongoing, and the increased collaboration between pharmaceutical companies, basic researchers, and clinical researchers has the potential to bring us closer to developing an optimum pharmaceutical approach for the treatment of Alzheimer’s disease. Keywords:Alzheimer’s disease, astrocytes, NSAIDs, X-Rays.

ABSTRACTEight Noctuidae species; Amphipyra herrichschaefferi Hacker and Pek, Catocala amnonfriedbergi Kravchenko et al.,Cucullia splendida Cramer, Lacanobia oleracea (Linnaeus), Lophotyna albosignata Moore, Characoma ruficirra Hampson,Simplicia caeneusalis (Walker) and Noctua orbona Hufnagel are newly added to the Himalayan fauna and five to India. Inaddition, taxonomic notes of all the eight recorded, little known Noctuids are discussed with the description of male and femalegenitalia. Figures illustrating adults and both sexes’ genitalia are also provided.Keywords: Taxonomic, New records, Himalaya.

ABSTRACT Amnesia is one of the most common side effects of benzodiazepines. It is known that benzodiazepines decrease the abilities to induced memory traces. Amnesic effect of diazepam on a variety of memory tasks is well known. Benzodiazepines induce anterograde amnesia in both humans and animals. The aim of our study was to compare the effects of three doses diazepam on learning and memory processes using active and passive avoidance tests. The male Wistar rats (9 per group, with body weight 180-220g) treated intraperitoneally with: 1st Saline 0.1ml/100g (controls); 2nd Diazepam 1.0mg/kg; 3rd Diazepam 2.5mg/kg; 4th Diazepam 5.0mg/kg. The animals were trained in shuttle-box and step-through apparatus manufactured by UgoBasile, Italy. In shuttle-box active avoidance tests the following parameters were observed: number of conditioned stimuli responses (avoidances), number of unconditioned stimuli responses (escapes) and number of intertrial crossings. In step-through passive avoidance tests the latency of reaction was calculated in seconds (180 ± 2 s). The comparison between the groups was made by Instat computer program. In shuttle-box active avoidance test the rats with diazepam in all studied doses decreased the number of conditioned and unconditioned stimuli responses and intertrial crossings on learning and memory tests compared to the control group. In step-through passive avoidance test the animals treated with the highest dose of diazepam significantly decreased the latency of reaction on learning compared to the control group. All experimental groups with diazepam decreased latency of reactions on short memory test. Our results allow us to conclude that diazepam dose-dependently impaired learning and memory processes in rats. Keywords: Diazepam, Amnesia and Rats.

ABSTRACTFragment-based drug discovery (FBDD) represents a logical and efficient approach to lead discovery and optimisation.It construct a drug leads from small molecular fragments and gaining momentum in both large pharmaceutical companies andbiotechnology laboratories as a complementary approach to traditional screening. This is because fragment-based approachesrequire significantly fewer compounds to be screened and synthesized, and are showing a high success rate in generatingchemical series with lead-like properties. In this it is a highly efficient method for drug discovery, and the techniques which arepopular in the past few years. In this review, I describe how a variety of approaches in fragment-based lead discovery — byNMR, X-ray crystallography, mass spectrometry, functional screening, in silico screening have produced drug leads. Theexamples show that the technique can reliably generate potent molecules, there is still much work to be done to maintain theefficiency of molecules’ binding affinities as fragments are linked, expanded, and otherwise improved.Keywords: FBDD, Scaffold based drug design, Screening fragments, Fragment growing, Target proteins.