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| REVIEW ARTICLES |
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Liver X Receptor: A novel therapeutic target |
p. 135 |
MB Patel, NA Oza, IS Anand, SS Deshpande, CN Patel DOI:10.4103/0250-474X.41445 PMID:20046702The liver X receptors α and β are orphan nuclear receptors that are key regulators in maintaining cholesterol homeostasis. Originally they were found to play an important role in reverse cholesterol transport, a pathway for the removal of excess cellular cholesterol. However several groups have now shown that the liver X receptors also functions in lipid and carbohydrate metabolism, cellular differentiation, apoptosis and many immune responses. Tissue distribution of the two paralogues differs with liver X receptor β ubiquitously expressed, while liver X receptor α is confined to the liver, kidney, intestine, spleen, adipose tissue, macrophages and skeletal muscle. The endogenous ligands for the liver X receptors are certain oxidized derivatives of cholesterol, the oxysterols. Upon activation by oxysterols, the receptors form obligate heterodimers with retinoid X receptors α, β and γ; and become competent to activate the transcription of target genes. |
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Strategies for enhanced drug delivery to the central nervous system  |
p. 145 |
V.S.N.M Dwibhashyam, AN Nagappa DOI:10.4103/0250-474X.41446 PMID:20046703Treating central nervous system diseases is very challenging because of the presence of a variety of formidable obstacles that impede drug delivery. Physiological barriers like the blood-brain barrier and blood-cerebrospinal fluid barrier as well as various efflux transporter proteins make the entry of drugs into the central nervous system very difficult. The present review provides a brief account of the blood brain barrier, the P-glycoprotein efflux and various strategies for enhancing drug delivery to the central nervous system. |
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| RESEARCH PAPERS |
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3D-QSAR CoMFA study of some heteroarylpyrroles as possible anticandida agents |
p. 154 |
PC Sharma, SV Sharma, Archana Sharma, B Suresh DOI:10.4103/0250-474X.41447 PMID:20046704A three dimensional quantitative structure-activity relationship study using the comparative molecular field analysis method was performed on a series of 3-aryl-4-[α-(1H-imidazol-1-yl) aryl methyl] pyrroles for their anticandida activity. This study was performed using 40 compounds, for which comparative molecular field analysis models were developed using a training set of 33 compounds. Database alignment of all 33 compounds was carried out by root-mean-square fit of atoms and field fit of the steric and electrostatic molecular fields. The resulting database was analyzed by partial least squares analysis with cross-validation; leave one out and no validation to extract optimum number of components. The analysis was then repeated with bootstrapping to generate the quantitative structure-activity relationship models. The predictive ability of comparative molecular field analysis model was evaluated by using a test set of 7 compounds. The 3D- quantitative structure-activity relationship model demonstrated a good fit, having r 2 value of 0.964 and a cross validated coefficient r 2 value as 0.598. Further comparison of the coefficient contour maps with the steric and electrostatic properties of the receptor has shown a high level of compatibility and good predictive capability. |
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Antiinflammatory, analgesic and antipyretic activity of certain thiazolidinones |
p. 159 |
AD Taranalli, AR Bhat, S Srinivas, E Saravanan DOI:10.4103/0250-474X.41448 PMID:20046705The thiazolidin-4-one derivatives and the corresponding spiro compounds were synthesized from sulphanilamide and were evaluated for anti-inflammatory and analgesic activity in acute and sub acute models. Compounds were also evaluated for antipyretic and cyclooxygenase enzyme inhibitory activity. All the compounds showed significant antiinflammatory, analgesic and antipyretic activity at 100 mg/kg in all the models. The compounds B1, B2, B5, B6, and B8 showed maximum inhibition of COX-2 activity without inhibiting the COX-1 activity. The nimesulide was used as standard drug for comparison. The substitution at R, R 1 and R 2 with the functional groups Cl, OCH 3 , NO 2 and OH in the aromatic ring resulted in increased activity as compared to unsubstituted thiazolidin-4-ones. However the substitution at R 3 with spiro group did not improve the activity. The study suggests that COX-2 binding site may not be a rigid structure but might adopt to various related molecules. |
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Probable mechanism(s) of antifungal activity of SJA-95, a heptaene polyene antibiotic |
p. 165 |
SK Desai, SR Naik DOI:10.4103/0250-474X.41449 PMID:20046706A new strain, streptomyces sp. S. 24 was isolated from a soil sample collected from Japan. The strain produced heptaene polyene antibiotic, SJA-95, in submerged culture and found to elicit promising antifungal activity against yeasts, filamentous fungi and clinical isolates, both in vitro and in vivo. Experimental studies were carried out using biological methods to understand the probable mechanism(s) of antifungal activity of SJA-95. Our experimental findings suggest that SJA-95 binds more avidly to ergosterol, the sterol in fungal cell membranes, than to cholesterol found in mammalian cell membranes. Such preferential binding of SJA-95 to ergosterol might help to establish its usefulness as a chemotherapeutic agent with lesser adverse reactions. |
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Development of biodegradable starch microspheres for intranasal delivery |
p. 170 |
AV Yadav, HH Mote DOI:10.4103/0250-474X.41450 PMID:20046707Domperidone microspheres for intranasal administration were prepared by emulsification crosslinking technique. Starch a biodegradable polymer was used in preparation of microspheres using epichlorhydrine as cross-linking agent. The formulation variables were drug concentration and polymer concentration and batch of drug free microsphere was prepared for comparisons. All the formulations were evaluated for particle size, morphological characteristics, percentage drug encapsulation, equilibrium swelling degree, percentage mucoadhesion, bioadhesive strength, and in vitro diffusion study using nasal cell. Spherical microspheres were obtained in all batches with mean diameter in the range of above 22.8 to 102.63 μm. They showed good mucoadhesive property and swelling behaviour. The in vitro release was found in the range of 73.11% to 86.21%. Concentration of both polymer and drug affect in vitro release of drug. |
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Preparation and evaluation of buccoadhesive films of atenolol |
p. 175 |
BK Satishbabu, BP Srinivasan DOI:10.4103/0250-474X.41451 PMID:20046708This paper describes the preparation of new bilayered device comprising a drug containing mucoadhesive layer and a drug free backing layer. Bilaminated films were produced by a casting/ solvent evaporation technique. The mucoadhesive layer was composed of mixture of drug and sodium alginate with or without carbopol 934 P, and backing layer was made of ethyl cellulose. The double layer structure design was expected to provide drug delivery in a unidirectional fashion to the mucosa and avoid loss of drug due to wash out with saliva. The fabricated films were subjected to in vitro drug release, in vitro permeation through porcine buccal mucosa. The bilayered films were also evaluated for mucoadhesive strength, mucoadhesive time, folding endurance, hydration studies and tensile strength. |
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Development of fast dispersible aceclofenac tablets: Effect of functionality of superdisintegrants  |
p. 180 |
C Mallikarjuna Setty, D.V.K Prasad, V.R.M Gupta, B Sa DOI:10.4103/0250-474X.41452 PMID:20046709Aceclofenac, a non-steroidal antiinflammatory drug, is used for posttraumatic pain and rheumatoid arthritis. Aceclofenac fast-dispersible tablets have been prepared by direct compression method. Effect of superdisintegrants (such as, croscarmellose sodium, sodium starch glycolate and crospovidone) on wetting time, disintegration time, drug content, in vitro release and stability parameters has been studied. Disintegration time and dissolution parameters (t 50% and t 80% ) decreased with increase in the level of croscarmellose sodium. Where as, disintegration time and dissolution parameters increased with increase in the level of sodium starch glycolate in tablets. However, the disintegration time values did not reflect in the dissolution parameter values of crospovidone tablets and release was dependent on the aggregate size in the dissolution medium. Stability studies indicated that tablets containing superdisintegrants were sensitive to high humidity conditions. It is concluded that fast-dispersible aceclofenac tablets could be prepared by direct compression using superdisintegrants. |
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Comparative molecular field analysis of benzothiazepine derivatives: Mitochondrial sodium calcium exchange inhibitors as antidiabetic agents  |
p. 186 |
AS Dasoondi, V Singh, SR Voleti, Meena Tiwari DOI:10.4103/0250-474X.41453 PMID:20046710Mitochondrial sodium calcium exchange inhibitors are novel agents in the treatment of type-II diabetes due to their glucose dependent efficacy. While the compounds of this class are expected to correct hyperglycemia, they do not lower basal blood glucose level, thus avoiding the serious consequences of hypoglycemia. The 3DQSAR analysis of benzothiazepines and their derivatives as mitochondrial sodium calcium exchange inhibitors was performed by comparative molecular field analysis to determine the structural factors required for the activity of these compounds. After performing a leave one out cross validation study, satisfactory results were obtained, with cross-validated q 2 and conventional r 2 values of 0.711 and 0.970, respectively. The results provided the tools for predicting the affinity of the related compounds, and guidance for the designing and synthesis of novel and potent mitochondrial sodium calcium exchange inhibitors as antidiabetic agents. |
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Albumin microspheres as an ocular delivery system for pilocarpine nitrate |
p. 193 |
Sudha Rathod, SG Deshpande DOI:10.4103/0250-474X.41454 PMID:20046711Pilocarpine nitrate loaded egg albumin microspheres were prepared by thermal denaturation process in the size range of 1-12 µm. A series of batches were prepared to study factors, which may affect the size and entrapment efficiency of drug in microspheres and optimized the process. Drug loaded microspheres so obtained were evaluated for their size, entrapment efficiency, release rate and biological response. Electron photomicrographs were taken (8000X) to study the morphological characteristics of microspheres. The entrapment and encapsulation of pilocarpine after process optimization was found to be 82.63% and 62.5% respectively. In vitro dissolution rate studies revealed that the release of drug from the microspheres followed spherical matrix mechanism. Biological response of microspheric suspension was measured by reduction in intraocular pressure in albino rabbit eyes and compared with marketed eye drops. Various pharmacokinetic parameters viz. onset of action, duration of action, Tmax and AUC were studied. A measurable difference was found in the mean miotic response, duration and AUC of pilocarpine nitrate microspheric suspension. |
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Rapid and simple RPHPLC method for the estimation of metformin in rat plasma |
p. 198 |
MM Wanjari, AW There, MR Tajne, CT Chopde, SN Umathe DOI:10.4103/0250-474X.41455 PMID:20046712A simple reverse phase high-performance liquid chromatographic method has been developed for determining the concentration of metformin in rat plasma. The method employs C 18 column (300 mm × 2.4 mm i.d.), ammonium acetate (0.15 M) and acetonitrile (90:10; pH-5.5; 1.0 ml/min) as mobile phase and ultraviolet detection at 236 nm. Acetonitrile was used to simultaneously deproteinize rat plasma and extract metformin. The assay was linear in the concentration range of 0.33 µg-16.6 µg/ml with co-efficient of correlation 0.994. The retention time was 4.7 min. The method was found to be precise (% CV <15%), accurate and suitable for pharmacokinetic study of orally administered metformin in rats. |
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Formulation and targeting efficiency of cisplatin engineered solid lipid nanoparticles |
p. 203 |
RC Doijad, FV Manvi, DM Godhwani, R Joseph, NV Deshmukh DOI:10.4103/0250-474X.41456 PMID:20046713The present study is aimed at the overall improvement in the efficacy, reduced toxicity and enhancement of therapeutic index of cisplatin. Solid lipid nanoparticulate delivery system of cisplatin has been developed by microemulsification method by using stearic acid, soy lecithin 95% and sodium glycolate. The formulations were then characterized with respect to size and its surface morphology, zeta potential, entrapment efficiency, in vitro drug release profile, in vivo drug targeting studies and its stability under specific conditions. The formulated solid lipid nanoparticles were oval with a diameter ranging from 250 nm to 500 nm. The lowest entrapment efficiency was found to be 47.59% and highest was found to be 74.53%. The zeta potential was in the range of -9.8 to -11.2 mv. In vitro release study was analyzed using various mathematical models. Highest cumulative percent drug release was observed with F-1 (97.22 %) and lowest with F-4 (78.43%) in 16 h. The in vivo result of formulated solid lipid nanoparticles of cisplatin reveals that the drug is preferentially targeting to liver followed by brain and lungs. |
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Synthesis of novel indolyl-pyrimidine antiinflammatory, antioxidant and antibacterial agents |
p. 208 |
SS Panda, P.V.R Chowdary DOI:10.4103/0250-474X.41457 PMID:20046714A number of chalcones were synthesized by reacting indole-3-aldehyde, prepared by Vilsemeir Haack reaction with 4-substituted acetophenone in NaOH solution in ethanol. These chalcones were immediately reacted with urea, thiourea and guanidine hydrochloride in presence of concentrated hydrochloric acid as reagent to obtain the corresponding hydroxy, thio and amino pyrimidines. The synthesized heterocyclics were characterized on the basis of physical, chemical tests and spectroscopic data and were tested for the acute antiinflammatory activity, antioxidant, antibacterial activity using carragenan-induced rat paw oedema method, DPPH (diphenylpicrylhydrazyl) radical scavenging method and cup plate method using Muller-Hinton agar media respectively. Evaluation of the compounds revealed remarkable antiinflammatory activity reflected by their ability to reduce the carragenan-induced inflammation in rats, appreciable antioxidant activity and also antibacterial activity was observed. |
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Studies on indomethacin intraocular implants using different in vitro release methods |
p. 216 |
J Balasubramaniam, A Srinatha, JK Pandit DOI:10.4103/0250-474X.41458 PMID:20046715Intra ocular implants of sodium alginate alone and in combination with hydroxypropylmethylcellulose with or without calcium chloride were formulated with indomethacin as a model drug. The drug release from the implants was evaluated using static method, continuous flow through apparatus (developed in house), USP dissolution and agar diffusion. Except in the static method, indomethacin particle size did not impart any effect on the drug release. In agar diffusion method, an increase in agar concentration from 1 to 2% resulted in a significant decrease (P<0.005) in the amount of drug released. Inclusion of hydroxypropylmethylcellulose (33.3, 41.6 and 50% w/w), resulted in decrease of indomethacin release irrespective of the method of dissolution study. The agar diffusion method and the continuous flow through methods seem to simulate to a certain extent the in vivo conditions as far as the placement of the device and the hydrodynamic diffusion layer around the intra ocular implant is concerned. The static method and USP method affected the hydrodynamic diffusion layer either too slowly or too fast. |
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| SHORT COMMUNICATIONS |
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Hydrolytic degradation profile and RP-HPLC estimation of cilostazol in tablet dosage form |
p. 222 |
PK Basniwal, PK Shrivastava, Deepti Jain DOI:10.4103/0250-474X.41459 PMID:20046716A simple, selective, precise and stability-indicating high-performance liquid-chromatographic method of analysis of cilostazol in pharmaceutical dosage form was developed and validated. The solvent system consisted of 10 mM phosphate buffer (pH 6.0):acetonitrile:methanol (20:40:40). Retention time of cilostazol in C18 column was 5.7 ± 0.1 min at the flow rate 1.3 ml/min. Cilostazol was detected at 248 nm at room temperature. The linear regression analysis data for the calibration plots showed good linear relationship with correlation coefficient value, r 2 =0.9998 in the concentration range 100-3200 ng/ml with slope 43.45 intercept 156.75. The method was validated for linearity, range, accuracy, precision and specificity. Cilostazol was determined in tablet dosage form in range of 99.58-100.67% with 0.4600 standard deviation. Stress studies were conducted in acid and alkali hydrolysis with gradual increasing concentration. Cilostazol was found to be stable in various concentrations of acidic and alkaline. |
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Formulation and in vitro evaluation of floating capsules of theophylline |
p. 224 |
SB Bhise, NH Aloorkar DOI:10.4103/0250-474X.41460 PMID:20046717Sustained release floating capsules for theophylline were fabricated using drug:polymer ratio of 30:70. The hydrocolloids were used in different proportions and four formulations were prepared. These formulations were optimized on the basis of buoyancy, matrix integrity, duration of floating and in vitro drug release. All the four formulations showed good buoyancy and matrix integrity. The duration of floating was more than 12 h for all formulations. In vitro drug release study of these formulations indicated controlled release of theophylline and about 76 percent drug was released at the end of 12 h. |
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Antihyperglycemic activity of various fractions of Cassia auriculata linn. in alloxan diabetic rats |
p. 227 |
SJ Surana, SB Gokhale, RB Jadhav, RL Sawant, Jyoti B Wadekar DOI:10.4103/0250-474X.41461 PMID:20046718Present work describes the potent antidiabetic fraction from flowers of Cassia auriculata Linn. Hydromethanolic extract along with its ethyl acetate and n-butanol fractions were evaluated for antidiabetic activity in alloxan-induced diabetes in rats. The n-butanol fraction exhibited significant reduction (p<0.001) in blood glucose levels and was also found effective in restoring the blood lipids and proteins to normal level. The activity was found comparable with standard drug phenformin. The hydromethanolic extract and its fractions were subjected to preliminary qualitative chemical investigations which indicated the presence of phenolic compounds, carbohydrates, tannins, steroids and amino acids. |
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Herb-drug interaction: A case study of effect of ginger on the pharmacokinetic of metronidazole in rabbit |
p. 230 |
JM Okonta, M Uboh, WO Obonga DOI:10.4103/0250-474X.41462 PMID:20046719The effect of ginger on the pharmacokinectic of metronidazole was studied using rabbits in a crossover study method. The relevance of this study borders on the wide use of ginger for culinary and phytotherapeutic purposes, and metronidazole that is commonly used for every gastrointestinal complain in our communities without prescription. Ginger significantly increased the absorption and plasma half-life, and significantly decreased the elimination rate constant and clearance of metronidazole ( P<0.05). Thus, in clinical practice, the patients should be advised on the serious implication of using both items together. |
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Development and validation of a HPTLC method for estimation of duloxetine hydrochloride in bulk drug and in tablet dosage form |
p. 233 |
Suneela S Dhaneshwar, P Deshpande, M Patil, G Vadnerkar, SR Dhaneshwar DOI:10.4103/0250-474X.41463 PMID:20046720Duloxetine hydrochloride is a potent dual reuptake inhibitor of serotonin and norepinephrine used to treat major depressive disorders. The present work describes a simple, precise and accurate HPTLC method for its estimation as bulk and in tablet dosage form. The chromatographic separation was carried out on precoated silica gel 60 F254 aluminium plates using mixture of chloroform:methanol (8:1 v/v) as mobile phase and densitometric evaluation of spots was carried out at 235 nm using Camag TLC Scanner-3 with win CAT 1.3.4 version software. The experimental parameters like band size of the spot applied, chamber saturation time, solvent front migration, slit width etc. were critically studied and optimum conditions were evolved. The drug was satisfactorily resolved with Rf value 0.11±0.01. The accuracy and reliability of the proposed method was ascertained by evaluating various validation parameters like linearity (40-200 ng/spot), precision (intra-day RSD 0.46-0.75%, inter-day RSD 0.46-1.59%), accuracy (98.72±0.20) and specificity according to ICH guidelines. The proposed method can analyse ten or more formulation units simultaneously on a single plate and provides a faster and cost-effective quality control tool for routine analysis of duloxetine hydrochloride as bulk drug and in tablet formulation. |
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Simultaneous UV spectrophotometric estimation of ambroxol hydrochloride and levocetirizine dihydrochloride |
p. 236 |
S Lakshmana Prabu, AA Shirwaikar, Annie Shirwaikar, C Dinesh Kumar, G Aravind Kumar DOI:10.4103/0250-474X.41464 PMID:20046721A novel, simple, sensitive and rapid spectrophotometric method has been developed for simultaneous estimation of ambroxol hydrochloride and levocetirizine dihydrochloride. The method involved solving simultaneous equations based on measurement of absorbance at two wavelengths 242 nm and 231 nm, the g max of ambroxol hydrochloride and levocetirizine dihydrochloride, respectively. Beer's law was obeyed in the concentration range 10-50 μg/ml and 8-24 μg/ml for ambroxol hydrochloride and levocetirizine dihydrochloride respectively. Results of the method were validated statistically and by recovery studies. |
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Antibacterial potential assessment of jasmine essential oil against E. coli |
p. 238 |
CC Rath, S Devi, SK Dash, RK Mishra DOI:10.4103/0250-474X.41465 PMID:20046722The antibacterial activity of Jasmine ( Jasminum sambac L.) flower hydro steam distilled essential oil, synthetic blends and six major individual components was assessed against Escherichia coli (MTCC-443) strain. The activity was bactericidal. Minimum inhibitory concentration was determined by tube dilution technique, and the Minimum inhibitory concentration ranged between 1.9-31.25 µl/ml. Phenolcoefficient of the oil, synthetic blends and components varied between 0.6-1.7. The activity of the chemicals was possibly due to the inhibition of cell membrane synthesis. |
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Hepatoprotective activity of Vitex trifolia against carbon tetrachloride-induced hepatic damage |
p. 241 |
BK Manjunatha, SM Vidya DOI:10.4103/0250-474X.41466 PMID:20046723Aqueous and ethanol extracts of leaf of Vitex trifolia was investigated for hepatoprotective activity against carbon tetrachloride induced liver damage. To assess the hepatoprotective activity of the extracts, various biochemical parameters viz., total bilirubin, total protein, alanine transaminase, aspartate transaminase and alkaline phosphatase activities were determined. Results of the serum biochemical estimations revealed significant reduction in total bilirubin and serum marker enzymes and increase in total protein in the animals treated with ethanol and aqueous extracts. However significant rise in these serum enzymes and decrease in total protein level was noticed in CCl4 treated group indicating the hepatic damage. The hepatoprotective activity is also supported by histological studies of liver tissue. Histology of the liver tissue treated with ethanol and aqueous extracts showed normal hepatic architecture with few fatty lobules. Hence the present study revealed that Vitex trifolia could afford significant protection against CCl 4 induced hepatocellular injury. |
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Synthesis and evaluation of L-glutamic acid analogs as potential anticancer agents |
p. 245 |
CL Viswanathan, S Deb, A Jain, T Lokhande, Aarti Juvekar DOI:10.4103/0250-474X.41467 PMID:20046724Four N-(benzenesulfonyl)-L-glutamic acid bis(p-substituted phenylhydrazides) were synthesized and evaluated for anticancer activity in vitro in DU-145 and PC-3 prostate cancer and in COLO-205 colon cancer cell lines by MTT assay. The analog with the nitro group substitution exhibited potent activity (% Inhibition 84.7 and 72.0 in DU-145 and PC-3 respectively at 80 mg/ml concentration). Another series of substituted 1-(benzenesulfonyl)-5-oxopyrrolidine 2-carboxamides (11a-f) were synthesized and evaluated for anticancer activity in vitro in colon (COLO-205), breast (Zr-75-1) and prostate (PC-3) cancer cell lines by MTT assay using adriamycin as standard. Test compounds 11a-c showed potent activity (% Inhibition 61.2 to 79.2 at 20 mg/ml and 67.2 to 87.2 at 40 mg/ml) in PC-3 cell line which is superior to the activity of Adriamycin. In comparison compounds 11d-f were less potent. In Zr-75-1 cell line 11a-e showed % inhibition ranging from 32.4 to 54.9 at 10 mg/ml concentration while in COLO-205 cell line 11a-f showed poor activity. |
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Spectrophotometeric determination of cefuroxime axetil from bulk and in its tablet dosage form |
p. 249 |
MV Shinde, SA Pishawikar, HN More DOI:10.4103/0250-474X.41468 PMID:20046725A simple rapid spectrophotometric method has been developed for estimation of cefuroxime axetil from bulk drug and tablet dosage form by using 1-nitroso-2-napthol and sodium hydroxide. The method is based on the formation of yellow-orange coloured complex of drug with 1-nitroso-2-napthol having absorbance maxima at 424 nm. The Beer's law is obeyed in the concentration range of 10-50 μg/ml of the drug but more precisely it obeys in the range of 10- 30 mg/ml. The slope and intercept values are 0.0101 and 0.0838, respectively. Results of analysis of this method were validated statistically and by recovery studies. The method is applied to the marketed tablet formulation. Result of analysis of tablet formulation given as percentage of label claim ±standard deviation is 99.17±1.57. The precision and accuracy was examined by performing recovery studies and was found to be 99.50±1.82. Sandell's correlation coefficient is calculated as 0.4434. The developed method is simple, sensitive and reproducible and can be used for routine analysis of cefuroxime axetil from bulk and tablet dosage form. |
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Stability-indicating simultaneous HPTLC method for olanzapine and fluoxetine in combined tablet dosage form |
p. 251 |
CR Shah, BN Suhagia, NJ Shah, DR Patel, NM Patel DOI:10.4103/0250-474X.41469 PMID:20046726A rapid, selective and stability-indicating high performance thin layer chromatographic method was developed and validated for the simultaneous estimation of olanzapine and fluoxetine in combined tablet dosage form. Olanzapine and fluoxetine were chromatographed on silica gel 60 F 254 TLC plate using methanol:toluene (4:2 v/v) as the mobile phase and spectrodensitometric scanning-integration was performed at a wavelength of 233 nm using a Camag TLC Scanner III. This system was found to give compact spots for both olanzapine (R f value of 0.63±0.01) and fluoxetine (R f value of 0.31±0.01). The polynomial regression data for the calibration plots showed good linear relationship with r 2 =0.9995 in the concentration range of 100-800 ng/spot for olanzapine and 1000-8000 ng/spot for fluoxetine with r 2 =0.9991. The method was validated in terms of linearity, accuracy, precision, recovery and specificity. The limit of detection and the limit of quantification for the olanzapine were found to be 30 and 100 ng/spot, respectively and for fluoxetine 300 and 1000 ng/spot, respectively. Olanzapine and fluoxetine were degraded under acidic, basic and oxidation degradation conditions which showed all the peaks of degraded product were well resolved from the active pharmaceutical ingredient. Both drugs were not further degraded after thermal and photochemical degradation. The method was found to be reproducible and selective for the simultaneous estimation of olanzapine and fluoxetine. As the method could effectively separate the drugs from their degradation products, it can be employed as a stability-indicating method. |
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Effect of hydroxylpropyl-β-cyclodextrin on solubility of carvedilol |
p. 255 |
BD Shewale, NP Sapkal, NA Raut, NJ Gaikwad, RA Fursule DOI:10.4103/0250-474X.41470 PMID:20046727The present study was undertaken to examine the effect of pH and concentration of hydroxypropyl-β -cyclodextrin on the solubility of carvedilol as it shows pH-dependent solubility. The equilibrium solubility of carvedilol in a series of solutions of varying pH (from 1.2 to 11) was determined and compared with the equilibrium solubility of carvedilol in the presence of 20% hydroxypropyl-β -cyclodextrin at same pH values. It was observed that solubility of protonated form is more than neutral molecule. Hydroxypropyl-β -cyclodextrin resulted in increased solubility at all the pH. But inclusion in the cavity of hydroxypropyl-β -cyclodextrin might depend upon charge state of the molecule. So it can be concluded that solubility of carvedilol, can be increased either by the addition of hydroxypropyl-β -cyclodextrin or by adding pH lowering agents. But both these methods if are to be used together, pH should be selected carefully. |
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UV and three derivative spectrophotometric methods for determination of ezetimibe in tablet formulation |
p. 258 |
Metreyi Sharma, Deepali V Mhaske, M Mahadik, SS Kadam, SR Dhaneshwar DOI:10.4103/0250-474X.41471 PMID:20046728UV, first, second and third derivative spectrophotometric methods have been developed for the determination of ezetimibe in pharmaceutical formulation. The solutions of standard and sample were prepared in methanol. For the first method, UV spectrophotometry, the quantitative determination of the drug was carried at 233 nm and the linearity range was found to be 6-16 µg/ml. For the first, second and third derivative spectrophotometric methods the drug was determined at 259.5 nm, 269 nm and 248 nm with the linearity ranges 4-14 µg/ml, 4-14 µg/ml and 4-16 µg/ml. The calibration graphs constructed at their wavelength of determination were found to be linear for UV and derivative spectrophotometric methods. All the proposed methods have been extensively validated. The described methods can be readily utilized for the analysis of pharmaceutical formulation. There was no significant difference between the performance of the proposed methods regarding the mean values and standard deviations. |
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Kinetics of autoxidation of an oil extract from Terminalia catappa |
p. 260 |
EO Omeje, GB Okide, CO Esimone, U Ajali DOI:10.4103/0250-474X.41472 PMID:20046729Soxhlet extractor was used in the extraction of oil from milled seeds of Terminalia catappa using petroleum ether (40-60°). The optimal oil yield was 56.71±1.66% with a viscosity of 40.79±1.05 centipoises. Other parameters of the oil were found as follows; specific gravity-0.9248, refractive index-1.4646, acid value-3.35, peroxide value-8.6, saponification value-166.2, and unsaponifiable matter-1.46. The crude oil extract was water-degummed, bleached and deodorized to generate what we called refined oil. Autoxidation of the crude and refined T. catappa oil extract was done at five different temperatures of 0±0.1°, 20±0.1°, 40±0.1°, 60±0.1° and 80±0.1° and also in the presence of pure a-tocopherol at a concentration of 1.0% (w/v) by measuring peroxide value variations over 96 h. In all evaluations, the refined oil exhibited lower tendency towards autoxidation but not at temperatures above 60±0.1°. The use of Arrhenius equation revealed generally very low activation energies of 0.0261 cal/deg×mol and 0.0122 cal/deg×mol for crude oil and antioxidant-treated crude oil, respectively and 0.0690 cal/deg×mol and 0.0177 cal/deg×mol for the refined oil. This study indicates T. catappa seed oil to be potential pharmaceutical oil with excellent characteristics. |
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Development and validation of RP-HPLC method for simultaneous estimation of atorvastatin calcium and fenofibrate in tablet dosage forms |
p. 263 |
N Jain, R Raghuwanshi, Deepti Jain DOI:10.4103/0250-474X.41473 PMID:20046730A reverse phase high performance liquid chromatographic method was developed for the simultaneous estimation of atorvastatin calcium and fenofibrate in tablet formulation. The separation was achieved by Luna C18 column and methanol:acetate buffer pH 3.7 (82:18 v/v) as mobile phase, at a flow rate of 1.5 ml/min. Detection was carried out at 248 nm. Retention time of atorvastatin calcium and fenofibrate was found to be 3.02+0.1 and 9.05+0.2 min, respectively. The method has been validated for linearity, accuracy and precision. Linearity for atorvastatin calcium and Fenofibrate were in the range of 1-5 μg/ml and 16-80 μg/ml, respectively. The mean recoveries obtained for Atorvastatin calcium and fenofibrate were 101.76% and 100.06%, respectively. Developed method was found to be accurate, precise, selective and rapid for simultaneous estimation of atorvastatin calcium and fenofibrate in tablets. |
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Development and evaluation of hepatoprotective polyherbal formulation containing some indigenous medicinal plants |
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PM Dandagi, MB Patil, VS Mastiholimath, AP Gadad, RH Dhumansure DOI:10.4103/0250-474X.41474 PMID:20046731The present study explores the hepatoprotective activity of various extracts of Ferula asafoetida , Momordica charantia Linn and Nardostachys jatamansi against experimental hepatotoxicity. Polyherbal suspensions were formulated using extracts showing significant activity and evaluated for both physicochemical and hepatoprotective activity in comparison with LIV-52 as standard. Petroleum ether (60-80°), chloroform, benzene, ethanol and aqueous extracts of Ferula asafetida , Momordica charantia Linn and Nardostachys jatamansi were evaluated for hepatoprotective activity against carbon tetrachloride-induced liver toxicity in Wistar rats. Polyherbal suspensions were prepared by the trituration method using a suspending agent and other excipients. Formulation F3 has shown significant hepatoprotective effect by reducing the elevated serum enzyme levels such as glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase. These biochemical observations were supplemented by histopathological examination of liver sections. Various parameters evaluated for all formulations were within the official specifications. Experimental data suggested that treatment with formulation F3 enhances the recovery from carbon tetra chloride-induced hepatotoxicity. From these results it may be concluded that the F3 formulation (containing chloroform, petroleum ether and aqueous extracts of Ferula asafetida , petroleum ether and ethanol extracts of Momordica charantia Linn. and petroleum ether and ethanol extracts of Nardostachys jatamansi ) demonstrated significant hepatoprotective activity, that might be due to combined effect of all these extracts. |
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