Karnataka

Inflammation plays key role in various diseases such as asthma, atherosclerosis and rheumatoid arthritis. Inflammation is defined as the local response of living mammalian tissues to tissue injury due to any agent. It is a body defense reaction in order to eliminate or limit the spread of injurious agent as well as to remove the consequent necrosed cells and tissues. Leucas aspera is a used orally as stimulant, anthelmintic, laxative, diaphoretic, for the treatment of headache, asthma, and bronchitis. The decoction of roots, stem of Leucas aspera is used orally for high fevers, for influenza, and for malarial fevers. Cassia tora commonly is used as tonic, carminative and stimulant. According to Ayurveda the leaves and seeds are acrid, laxative, antiperiodic, anthelmintic, ophthalmic, liver tonic, cardiotonic and expectorant. This study was aimed to evaluation of anti-inflammatory activity of the roots of Leucas aspera and Cassia tora.

The hepatoprotective activity of the aqueous extracts of S. venulosa (AESV) and S. wallichiana (AESW) leaves on carbon tetrachloride (CCl4)-induced liver damage in albino rats was investigated. Animals were pretreated with the AESV (250 and 500 mg/kg body weight) and AESW (250 and 500 mg/kg body weight) for 15 days and then challenged with CCl4 (1 ml/kg body weight) in olive oil (1:1 v/v) on the 15th day. The degree of protection was measured by using biochemical parameters such as serum glutamate oxalate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total protein and total bilirubin. Further the effects of both the extracts on catalase (CAT), peroxidase (Px) and superoxide dismutase (SOD) were estimated in both CCl4 treated and extract treated groups. Oral administration of AESV and AESW (500 mg/kg body weight) significantly protected from CCl4-induced elevation in SGOT, SGPT, ALP, total bilirubin, total protein and decrease in the activities of hepatic antioxidant enzymes namely SOD, CAT and Px. The extracts (AESV and AESW at 500 mg/kg body weight) also protected against histopathological damage induced by CCl4 such as distorted hepatocytes and necrosis. The present study suggests that AESV has potent antioxidant and hepatoprotective activity when compared to AESW. Key words: Schefflera species, hepatoprotective, CCl4, antioxidant enzymes.

This research has focused on the incorporation of the thiadiazole moiety into versatile pyridine ring because of their biological properties. In order to explore the possibilities of some altered biological action author envisaged that by designing the Schiff base derivatives of 1, 3, 4-thiadiazole moiety may exhibit anticancer properties. These novel 1,3,4-thiadiazole Schiff base compounds have been synthesized by microwave-assisted synthesis and screened for their cytotoxicity on HeLa, HepG2 and MCF7 cancer cell lines.The key intermediate 2-(4-fluorophenyl)pyridine-3-carboxylic acid was obtained by hydrolysing the ester 3 in presence of KOH and methanol.Thus obtained compound 4 was treated with thiosemicarbazide and phosphorous oxychloride and cyclized in microwave inorder to get the intermediate 5-[2-(4-fluorophenyl) pyridin-3-yl]-1, 3, 4-thiadiazol-2-amine. The amine 5 was reacted with different aldehydes (a-h) in presence of catalytic amount of acetic acid and obtaineda series of novel Schiff base derivatives 6a-6h. These compounds were characterized by MS, 1H-NMR,IR and elemental analysis. Most of the compounds in this series have exhibited moderate cytotoxicity onall the three human cell lines at different concentrations, but two compounds 6f and 6h showed good inhibition towards liver carcinoma cell lines having IC50 of 23.8µMand 13.4µM respectively.

A simple, sensitive, accurate and specific stability-indicating high-performance liquid chromatographic method was developed and validated for the estimation of clopidogrel bisulphate in bulk. In the present study, extensive testing of clopidogrel bisulphate in different stress conditions were carried out as per the ICH guidelines Q1A (R2). The system consisted of a pump (Shimadzu, prominence, LC20AD), with 20µl sample injector, along with a PDA (Shimadzu, prominence, SPDM20A) detector at a wavelength of 254nm. Data was compiled using Shimadzu LC Solution software. The degraded products formed under various stress conditions were separated successfully from the drug by using a PHENOMENEX C8 Column (150 x 4.6mm, 5µm) with binary gradient conditions. Acetonitrile: phosphate buffer of pH 2.0 was used as mobile phase at flow rate of 1.2ml/min. Clopidogrel bisulphate was exposed to various stress conditions like oxidation, hydrolysis, photolysis and neutral decomposition. Clopidogrel bisulphate, which was found to degrade considerably in acidic, photo and oxidative conditions, was found to be stable in alkaline and neutral conditions. Apart from the formation of minor degraded products under accelerated conditions, the drug was reasonably stable in solid state. A good linear relationship over the concentration range of 150-500µg/ml was shown. Validation of the method was carried out as per the ICH guidelines. The method developed was found to be precise, accurate, specific and selective. Clopidogrel bisulphate showed degradation in 5M Hydrochloric acid at 80oC, in 3% hydrogen peroxide for 5min the drug showed around 35% of degradation, when exposed to sunlight for 15 min, formed around 25-30% of degradation products. Statistical analysis shows that the method is reproducible and selective for the estimation of clopidogrel bisulphate in dosage form.

In order to achieve rapid action and sustained release, we have fabricated dual type of mini-tablets of Diclofenac Sodium enclosed in a single capsule. 10 formulations of rapid release (IF1-10) mini tablets were prepared using sodium starch glycolate, Cross povidone and Micro crystalline cellulose. 12 formulations of sustained release (SF1-12) mini tablets were prepared by using HPMC, carbopol, Ethyl cellulose, xanthan gum and guar gum. All formulations were evaluated for pre-compression and post-compression parameters. Drug Excipient interaction was determined by FTIR, Short term stability studies were carried out at 40 0C /75 % RH for 3 months. Pre-formulation and studies conformed that all formulations showed better flow property. In vitro studies showed that all mini tablets in combination released more than 55 % within 30 min whereas marketed tablet Voveran SR 100 showed only 11 % release indicating the rapid drug release and the release was extended up to 80 % in 20th hour indicating the sustainability of the release. Natural polymers, Xanthan gum and guar gum containing formulations showed above 90 % in 12th hour indicating little rapid drug release when compared to synthetic polymers. FTIR report indicated no interaction of drug with excipients. Stability studies showed no significant loss in drug content, release profile and physical appearance. Hence it can be concluded that, the release profiles duel type mini tablets were quite promising for once a day formulation.

A series of novel triazole fused thienopyrimidine derivatives are synthesized by Gewald reaction, which are well characterized by IR, 1HNMR, 13CNMR and Mass spectral analysis. These compounds are screened for their in vitro anti-tubercular and antibacterial activities. Most of these compounds exhibited MIC values in the range of 20 – 100 µM against Mycobacterium tuberculosis H37Rv. In the series, compound 5c was most active with MIC 20 µM. Furthermore, the title compounds were screened for antibacterial activity against Staphylococcus aureus ATCC 29213 (gram positive) and Escherichia coli ATCC 25922 (gram negative) bacteria. Some of these compounds exhibited MIC values in the range 8 - 64µM. Compound 5c was found to be the most active with an MIC of 5 and 8µM respectively.

Colon targeted drug delivery system is capable of protecting the drug in route to the colon i.e. drug gets released and absorbed once it reaches the colon. A multiparticulate system combining pH sensitive property and biodegradability has been investigated to prepare and evaluate Eudragit S-100 coated Sodium alginate microspheres for colon targeting of Tramadol Hydrochloride. Uncoated Tramadol Hydrochloride microspheres were prepared by ionotropic gelation technique using different ratios of Tramadol Hydrochloride and Sodium alginate. Coated Tramadol Hydrochloride microspheres were prepared by coacervation phase separation technique using different ratios of uncoated Tramadol Hydrochloride and Eudragit S-100/ Eudragit L-100. Uncoated and coated Tramadol Hydrochloride microspheres were evaluated for percentage yield, particle size, surface morphology, flow properties, drug content and entrapment efficiency and were found to be within the acceptable range. The uncoated microspheres sustained the release upto 8 hrs whereas coated microspheres sustained the release upto 12 hrs in a pH progression medium mimicking the condition of GIT. The drug release from MC4 formulation coated with Eudragit S-100 (1:4) showed desired rate as there was no drug release observed upto 4-5 hrs, while in colonic fluid controlled drug release was observed releasing about 69.66 % after 12 hrs. The release kinetics followed Peppas showing Super Case II transport. Stability studies suggested formulations were stable. It is concluded from the present investigation that Eudragit S-100 coated Sodium alginate microspheres are promising controlled release carriers for colon targeted delivery of Tramadol Hydrochloride.

The present work reports on the preparation of ethyl cellulose (EC)-pluronic F127 (PF127)-based tableted floating microspheres by the oil-in-water emulsion solvent evaporation method for the controlled release of acyclovir (ACV). Microspheres of this study were characterized by Fourier transform infrared (FTIR) spectroscopy to investigate the chemical interactions of ACV with the polymer, floating behavior, scanning electron microscopy (SEM) for morphology of the microspheres, differential scanning calorimetry (DSC) for investigating their thermal properties  and X-ray diffraction (XRD) as well as. In vitro release experiments of microspheres were performed in acidic pH 1.2 media to understand the release profiles of ACV. The selected sets of microspheres were compressed into tablets using the compressible excipients and their in vitro release performances were evaluated in pH 1.2 media.

Terbinafine hydrochloride (TFH), is a potent antifungal agent of the allylamine class with broad spectrum activity against yeasts, dimorphic fungi, molds, and dermatophytes. A new, simple, rapid, selective, precise, accurate, and stability indicating high performance liquid chromatographic method has been developed for the determination of terbinafine hydrochloride (TFH) in pharmaceuticals. The assay was performed using an Zorbax Eclips XDB C-18 (3.5 µm, 4.6 × 150 mm i.d.,) column at 30ºC temperature with UV-detection at 222 nm. A mobile phase consisting of buffer (1000 mL water, 2 mL triethylamine, pH 3.4 adjusted with trifluoroacetic acid.), isopropyl alcohol and methanol (40:12:48, v/v/v), was used in the assay at a flow rate of 1 mL min-1. The method was validated and system suitability parameters were investigated. An excellent linearity was obtained over the concentration range 1 - 80 μg mL-1 TFH with limits of detection (LOD) and quantification (LOQ) values of 0.3 and 1.0 mg mL-1, respectively. The proposed method were applied successfully to the determination of TFH in tablets. The results obtained were in good agreement with those obtained by a reference method, with high precision and without any detectable interference from tablets excipients. The validity and reliability of the proposed methods were further assessed by the recovery studies via a standard addition method. In addition, forced degradation of TFH was conducted in accordance with the ICH guidelines. Acidic, basic water hydrolysis, thermal stress, peroxide and photolytic degradation were used to assess the stability indicating power of the method. Slight degradation was observed during oxidative degradation and no degradation was observed under other stress conditions.

This research aimed to evaluate a new approach for preparation of in situ gel and to design innovative peroral delivery systems for Ranitidine Hydrochloride (RHCl) able to enhance the control release. The present study was carried out to optimize and evaluate an oral in-situ gel containing ranitidine HCl with Pluronic F-127 and hydrophilic HPMC E50 by the simple mixing method. The compatibility of the polymers was proved by FTIR. The prepared in-situ gel formulations were tested for their physicochemical characteristics such as clarity, gel strength, gelation temperature, drug content, sol-gel transition time and in vitro release studies of ranitidine HCl-loaded in-situ gel formulation in phosphate buffer (pH 1.2 and 7.4. ) were performed using a modified diffusion cell across dialysis membrane. The prepared formulations were clear and Gel strength ranges from 31±1.6 to 33±1.2. The drug content for the prepared formulations was 97.23% to 99.02%.Then the Drug release at 12 h is 98.25 and thus shown controlled release.