International Journal of Pharmaceutical Sciences and Drug Research

44-54

Authors: Srivastava AK1*, Kaushik D1, Shrivastava AK2, Lal VK3

Medicinal plants may serve as a vital source of potentially advantageous new compounds for the development of effective therapy to action an array of kidney problems. Abounding herbs accept been accurate to be accomplishing as nephroprotective agents while abounding added are claimed to be nephroprotective but there is abridgement of any such accurate affirmation to abutment such claims. Developing a satisfactory herbal therapy to treat serve renal disorders requires systematic investigation of backdrop like acute renal failure, nephritic syndrome and chronic interstitial nephritis. Herbal medicines acquire alleviative backdrop due to the presence of their chemical components. An amount of extracts of accustomed articles and comestible antioxidants accept been appear to appearance careful furnishings adjoin nephrotoxicity. Following herbal drugs accept apparent their almighty nephroprotective aftereffect due their antioxidant, diuretic, anti-inflammatory, antispasmodic properties. The present review is aimed to elucidate the list of nephroprotective medicinal plants, which are scientifically proved in treating renal disorders.

64-67

Authors: M Sheik Noor Mohamed, K Jaikumar, D Anand, P Saravanan*

Macrophages are tissue-based phagocytes that play the central role in initiating defence mechanism of host immunity. Macrophage expresses inducible nitric oxide synthase (iNOS) that inhibit pathogen replication by releasing a variety of effector molecules which includes nitric oxide (NO). In the present study ethanol extract of Piper nigrum Linn. (white pepper) seed was investigated for its cytotoxicity and in vitro immunomodulatory properties using cell proliferation and NO determination assay with J774a-1, macrophage cell line. The ethanol seed extract was found to exhibit toxicity at higher concentrations of 50µg/ml and 100µg/ml. The seed preparation was observed to enhance both, the proliferation of macrophage cell with higher percentage proliferation of 29.24 at 12.5µg/ml and the production of NO with significant stimulation level of 47.74% at 12.5µg/ml compared to the control. Since the results show the modulator effect of Piper nigrum Linn. seed on macrophage cells, it could be considered to possess immunomodulatory potential.

72-78

Authors: N. I. Hulkoti*, T. C. Taranath

In this study we describe the phytofabrication of AgNps through a green route as a cost-effective, instantaneous and an eco-friendly approach using Petrea volubilis L. stem broth. The influence of physico-chemical parameters - contact time, stem broth quantity, pH, temperature, and silver nitrate concentration were studied and optimised to engineer, nanoparticles of diverse sizes. Nanoparticles were characterized by UV-Vis spectroscopy, FTIR, XRD, Zeta potential, EDS, and HRTEM. The characterization using HRTEM showed that, the nanoparticles were spherical and with increase in contact time, stem broth quantity, pH, and temperature, the NPs size minimised whereas escalation in silver nitrate concentration, increased their size. Capping molecules were negatively charged and the NPs were passably stable according to zeta potential readings and they were crystalline as per XRD data. According to FTIR analysis, the bio reduction was attributed to alcohol, ethers, carboxylic acids, and esters. The highest anti-bacterial activity was observed against S. aureus and S. typhi whose ZOI diameter was 13 mm at 100μl in both bacteria. The highest anti-fungal activity of silver nanoparticles was observed against A. flavus whose ZOI diameter was 9 mm at 100μl compared to P. chrysogenum which is 3 mm at 100μl. The stem broth did not show any anti-microbial activity for the microbes. Anti-microbial activity of AgNPs is due to its small size and high surface area. Our findings clearly discloses that sizes of silver nanoparticles can be varied by varying the physico-chemical parameters and the small sized nanoparticles so formed are promising antimicrobial agents and has a great potential in various medical applications.

83-89

Authors: Lipin Dev M S1, Darsan B Menon2*

The use of medicinal plants in the form of extracts and oils dates back to pre-historic times. The aim of the study was to determine the effect of Essential oil (EO) extracted from leaves of Plectranthus amboinicus on lung cancer cell line, A549. MTT assay was performed to check the efficacy of Essential oil to induce death in cancerous A549 cells and normal HEK293 cells. Acridine Orange/Ethidium Bromide staining, Hoechst staining and DNA fragmentation assays were used to confirm the apoptosis inducing ability of EO on A549 cells. RT-PCR and western blotting was performed to check the expression of pro- and anti-apoptotic factors. Calorimetric assay was done to check caspase-3 and caspase-9 activities. Essential oil at lower concentrations was found to induce cell death selectively in the lung cancer cells (IC50 = 10.74 µg/mL). The transcriptional expression studies of the pro-apoptotic Bax and anti-apoptotic Bcl-2; and the western blot analysis of pro-apoptotic BAK and BAD showed that EO upregulated the expression of pro-apoptotic factors and down regulated the expression of anti-apoptotic factors in A549 cells. Caspase-9 and 3 activities were found to be upregulated in the calorimetric studies. The down regulation of anti-apoptotic factors and upregulation of pro-apoptotic factors show that the Essential oil induced apoptosis in the lung cancer cells via the intrinsic or the mitochondrial pathway.

94-97

Authors: C. Girish1, Y. Narsimha Reddy2*

The purpose of the study was to test the acute oral toxicity of the different extracts of the plant Nigella sativa. Acute toxicity of petroleum ether, methanol and aqueous extracts of Nigella sativa was evaluated in Swiss mice. The acute toxicity studies were carried out based on OECD guidelines 423. The animals were administered orally with a single dose of 100, 250, 500, 750, 1000, 2000 mg/kg body weight of each extract. Signs of toxicity and mortality were noted after 1, 4 and 24h of administration of the extract for about 14 days. The highest dose administered (2000 mg/kg body weight) do not produce mortality or changes in general behaviour of the test animals. These results indicate the safety of the oral administration of petroleum ether, methanol and aqueous extracts of Nigella sativa.

10-16

Authors: Dipesh Patel*, Bhupendra Prajapati

The objective is to prepare extended release micro-pellets of the s-Metoprolol Succinate which is chirally pure molecules. Commercially Metoprolol Succinate is available the racemic mixture of the s and r isomers. Out of both the isomers s-isomer is predominantly responsible for the cardiac beta blocking activity. So to use the more desirable beta blocking activity of s-Metoprolol Succinate, extended release micro-pellets of the s-Metoprolol Succinate was prepared. Due to pure chiral molecules the dose was also reduced to half to that of the racemic mixture. Extended release micro-pellets of the s-Metoprolol Succinate was prepared by the fluid bed technology, in which s-Metoprolol Succinate along with binder and anti-adherent material was sprayed on the inert core. These drug loaded pellets of the s-Metoprolol Succinate was than coated with ethyl cellulose as extended release polymer, hypromellose as pore former and acetyl tri butyl as novel plasticizer and talc as an anti-adherent. The formulation was further optimized for drug release, as per USP recommended dissolution condition, using central composite design (CC). Results shows that at level of 58-66% w/w extended release coating with any studied concentration of acetyl tri butyl citrate and hypromellose gives desired drug release profile.

22-29

Authors: Y. Khatoon1*, M. Shaquiquzzaman2, V. Singh1, M. Sarafroz3

A series of 2, 5-disubstituted - 1, 3, 4 – oxadiazoles (4a-o) were synthesized on refluxing hydrazine carbothioamides with iodine and potassium iodide in ethanolic sodium hydroxide solution starting from methyl-3-amino-4-hydroxy benzoate via synthesis of an intermediate methyl-2-substitutedaryl-1, 3-benzoxazole-5-carboxylates and 2-substitutedaryl-1, 3-benzoxazole-5-carbohydrazides. The newly synthesized compounds were characterized on the basis of spectral (FT-IR, 1H-NMR, MS) and elemental analysis. All these compounds were screened for anticonvulsant activity using Maximal Electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) method. Anticonvulsant activity was shown by majority of the synthesized compounds when given i.p. to mice. Among the tested compounds 4e, 4j and 4o were considered to have potent anticonvulsant activity comparable to that of standard drugs Phenytoin and Carbamazepine. Compounds 4e, 4g, 4h, 4i, 4k and 4m passed the rota rod test successfully without any sign of neurological deficit.

34-37

Authors: Marimuthu S1, Sheik Noor Mohamed M1, Saravanan P1, Anand D1*, Rajarajan S2

The medicinal plants have played a vital role in drug discovery. Many plants are used traditionally for the treatment of different types of viral disorders and other infectious diseases. Herpes simplex virus (HSV) is a ubiquitous organism that causes infections in human populations throughout the world. It causes a variety of diseases ranging in severity from mild to life-threatening. The present study was to evaluate antiviral activity of Hypericum mysorense F. Heyne ethanolic leaf extract against herpes simplex virus type 2 (HSV-2) using HEp-2 cell line. The toxic free concentrations of ethanolic extract were determined using MTT assay, followed by anti HSV-2 activity and a positive control was maintained. 50µg/ml of ethanol extract was observed to be maximum non toxic free concentration against HEp-2 cell line and also exhibited significant inhibitory activity against HSV-2.

287-290

Authors: Mehul K. Bhatt1*, Nehal Shah2

The anti-urolithiatic action of Hygrophila salicifolia (Acanthaceae) was determined by ethylene glycol induced lithiasis. Ethylene glycolated water (0.75% v/v) was given to experimental animals for 28 days to produce stone in kidney. Methanolic extracts of Hygrophila salicifolia were given from the 1st day as inhibitory agent. Urinary parameters such as calcium, oxalate and inorganic phosphate level were raised by ethylene glycol where as test extract lowered down the raised level of these ions in urine. Methanolic extract of Hygrophila salicifolia also increased urinary magnesium concentration while raised concentration of serum creatinine was found to be cut down during the experiment. Methanolic extract of test drug was found impressively better from histological study. These results obtained from the study confirmed the anti-urolithiatic potential of Hygrophila salicifolia.

295-298

Authors: Lekhni Soni, Rupesh K Gautam*

The present investigation is aimed to evaluate anti-arthritic activity of the ethanol extract of root of Momordica charantia (EEMR) by using Freund’s complete adjuvant (FCA) induced arthritis model which is a extensively used model for in-vivo study of anti-arthritic activity. Arthritis assessment was carried out on basis of parameters i.e. arthritis score, joint diameter and paw volume. The standard drug was diclofenac sodium. The findings of present study showed that EEMR in dose of 400 mg/kg produced more significant reduction in arthritis score, joint diameter and paw volume as compare to 200 mg/kg. On the basis of results, it can be concluded that EEMR showed significant anti-arthritic activity. It may be due to presence of phytocompounds such as flavonoids, alkaloids, tannins etc.

249-253

Authors: Himanshu A Acharya*, Rakesh P Patel

Hydralazine hydrochloride has a half-life of 2 to 4 hours with an oral bioavailability of 26-50%. Since hydralazine has a demethylating effect on various suppressor genes, it can be used in various types of cancer to support chemotherapy. The purpose of this study was to optimize and evaluate floating tablets of hydralazine hydrochloride designed to prolong the gastric residence time and to provide controlled release of the drug for 24 h. The floating tablets of hydralazine hydrochloride were prepared by the wet granulation method. Polymers of hydroxy propyl methyl cellulose (HPMC K100M), HPMC K15M, carbopol 940 and sodium bicarbonate were used as the release retarding agents. This study investigated utility of a 3-factor, 3-level Box-Behnken design and optimization process for floating tablet of Hydralazine with 5 replicates of center points. Amount of HPMC K4 (Hydroxy Propyl Methyl cellulose), amount of sodium bicarbonate were selected as the independent variables whereas total floating time (TFT), T90, % cumulative drug release at 24 hours, and T20, Q1 were selected as dependent variables. Non-Fickian diffusion release transport was confirmed as the release mechanism for the optimized formulation and the predicted values agreed well with the experimental values. Drug excipient compatibility studies were investigated by FTIR, DSC and XRD. The produced tablets exhibited good floating time and controlled drug release over a period of 24 h. The resultant data were critically analyzed to locate the composition of optimum formulations. All predicted values of response variables of optimized formulation demonstrated close agreement with the experimental data during optimization procedure.

259-264

Authors: Susheel Thakur*, Nisha Thakur, Niladry Shekar Ghosh

Arthritis is the condition which is associated with inflammation of a joint, pain, swelling, and stiffness. Drug delivery to the target site remains a challenge due to ineffective drug delivery system. An attempt has been made to formulate and evaluate micro-emulgel for the effective drug delivery in the treatment of Arthritis. Micro-emulgel was loaded with Curcumin and Tinospora cordifolia to enhance bioavailability of extracts which have been widely used in the treatment of arthritis. Micro-emulgel was prepared by emulsion-solvent diffusion method using carbopol 940P as a gelling agent. Micro-emulsion was formulated using Liquid paraffin oil as oil phase; Tween 80 and Span 20 as surfactant and co-surfactant respectively. FTIR studies proved the compatibility between drug, excipient and carbopol. The Prepared micro-emulgel was subjected to various parameters such as pH, rheological studies, spreadability, thermodynamic stability tests, drug content, electro conductivity, and in-vitro release studies. The pH of all formulations was found near to the skin pH value. Viscosity and spreadability of F1 optimized formulation was found to be 146.5×103 cPs and 2.24 g×cm. From the in vitro drug release study, it was revealed that sustained release of formulation last up to 18 hours. F1 formulation showed the highest drug release of Curcumin (92.37%) and Tinospora cordifolia (90.75%). SEM images showed the diameter of oil globules of Micro-emulgel were in range of 1.50 to 2.13µm. Drug release kinetics showed the zero order drug release from the optimized F1 formulation. From the stability studies, F1 formulations had an excellent physical stability.

269-274

Authors: G. Rajeswari Gopal1*, G.I. Anuja2, P.G. Latha2, A. Jayakumaran Nair1, A. Gangaprasad4, P.R. Sudhakaran1, D. Muraleedharan3, G.M. Nair1

In the present study the roots and leaf ethanolic extracts of Chassalia curviflora were screened for their anti hepatotoxic and anti oxidant effects in experimentally induced liver injury by carbon tetra chloride. Liver serum marker enzymes as well as antioxidant enzymes mainly superoxide dismutase, catalase and glutathione levels were determined. The plant root and leaf ethanolic extracts at 50, 100, 200 mg concentrations significantly (**P ≤ 0.05) reduced the elevated serum hepato specific enzyme [serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), serum alkaline phosphatase (SAKP), serum bilirubin (SB)] and cholesterol levels induced by CCl4. Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and non enzymatic reduced glutathione (GSH) levels were increased whereas malondialdehyde (MDA) level was reduced by the extracts. Compared to the leaf extract, root extract significantly reduced serum hepato parameters and increased the levels of anti-oxidant enzymes in a dose dependent manner. The results were comparable to that of silymarin, reference drug used for the study. The histopathological studies also supported the biochemical findings. Acute toxicity studies revealed that it is safe for pharmacological uses upto 2000mg/kg. The present study scientifically validated the traditional use of plant root in hepatoprotection.

199-203

Authors: J. S. Shah1*, J. B. Patel2, S. Dani3

Coronary Artery Disease (CAD) occurs when the arteries of the heart that normally provide blood and oxygen to the heart are narrowed or even completely blocked due to clot formation. The Stenting implantation composes 84.2% of all Percutaneous coronary intervention (PCI). Despite the widespread use of these devices, bare metal stents (BMS) have been associated with a 20-30% restenosis rate which requires reintervention. In December 2006, US Food and Drug Administration cardiovascular experts concluded that for many patients, such as those with uncomplicated medical histories who undergo elective stenting of simple coronary blockages, drug-eluting stents remain a safe and appropriate therapy. Previously reports are suggestive of similar clinical outcomes for stainless steel and cobalt chromium bare metal stent. No reports are available for comparison of sirolimus eluting stainless steel stent and sirolimus eluting cobalt chromium stent. The present study was undertaken with the objective of comparative evaluation of Stainless Steel Stent (Sirolimus) and Cobalt Chromium Stent (Sirolimus) in Patient with Coronary Artery Disease. A single centric, retrospective, non-randomized study involving 118 patients who have undergone PCI from January 2011 to March 2012 implanted with either Sirolimus Stainless Steel Stent (SSSS) or Sirolimus Cobalt Chromium Stents (SCCS) were included in the study. Primary objective was to determine and compare the clinical outcome and rates of target vessel revascularization (TVR) in patients undergoing primary PCI for CAD patients who were treated with Sirolimus cobalt-chromium stents and Sirolimus stainless steel stents. The secondary outcomes of study were Major Adverse Cardiac Events, mortality at the end of 1 month, 6 month and 1 year of outcomes. At 1 month follow up there was no significant difference between two groups (p = 0.96). The individual clinical component showed no difference in occurrence of death (p = 0.29), MI (p = 0.29) and TLR (p = 0.96) at end of 6 month. The cumulative clinical outcome at 1 year rate of target vessel revascularization TVR (SSSS 1.75% versus SCCS 0%, p = 0.29), target lesion revascularization (SSSS 5.27% versus SCCS 1.63%, p = 0.27), and Major Adverse Cardiac Events (SSSS 22.80% versus SCCS 13.11%, p = 0.16). This study showed that among Coronary artery disease (CAD) patients undergoing primary percutaneous coronary intervention, sirolimus stainless steel stent showed similar efficacy and safety to sirolimus cobalt chromium stent.

210-217

Authors: CM Detroja1*, LD Patel2, PR Vasanani3

Factorial design enables researchers to study and understand how multiple factors affect a dependent variable, both independently and jointly. In present report, 33 factorial design was used to study the combined influence of three independent variables in preparation of Simvastatin loaded Poly (D, L Lactide -co- Glycolide) (PLGA) nanoparticles. Nanoparticles were prepared by nanoprecipitation method. The process variables like rate of addition of organic phase to aqueous phase, temperature, speed of magnetic stirrer and time to evaporate organic phase were kept constant throughout the investigation. The formulation variables like concentration of stabilizer (Polyvinyl alcohol), drug (Simvastatin): polymer ratio (PLGA), and organic (acetone): aqueous phase ratio were selected as independent variables. Prepared nanoparticles were evaluated for particle size (PS) and entrapment efficiency (EE). PS and EE were selected as dependent variables. The coded values of independent variables were subjected to multiple regressions to derive a second order polynomial equation (full model). After neglecting the non-significant terms from full model, F-Statistics was applied to set up reduce polynomial equation. Among the three independent variables, value of coefficient of drug: polymer ratio was found to be maximum. This revealed that major contributing variable for PS and EE in nanoparticles is drug: polymer ratio. Two dimensional contour plots and three dimensional response surface plots were established by varying levels of two factors and keeping the third factor at fixed level at a time. Thus the derived equation, surface response plot and contour plot helps in predicting the value of independent variables for optimum PS and EE in preparation of Simvastatin loaded PLGA nanoparticles.

223-228

Authors: Paras R. Vasanani1*, L. D. Patel2, Chetan M. Detroja3

Nanosuspensions are the dispersions of nanosized particles in a suitable vehicle prepared using surfactants or solubilizers to aid in nanosize distribution. Nanosuspension is best suited for dosage form development of poorly soluble drugs. According to the biopharmaceutical classification system, drugs with poor solubility fall either in BCS class II or BCS class IV. BCS class II drugs show poor solubility and good permeability; hence their bioavailability problems can be overcome by improving their solubility. Metaxalone is one such BCS class II drug from an oxazolidin-2-one class of centrally acting muscle relaxant drugs, indicated for relief of discomforts associated with acute, painful musculoskeletal conditions. Therefore, in present investigation, nanosuspension of Metaxalone has been formulated as an attempt to improve solubility and hence the overall bioavailability of Metaxalone. Media milling technique has been employed for nanosuspension preparation. Surfactant concentration (Poloxamer 407) and stirring time has been optimized using 32 factorial design to achieve desired particle size and saturation solubility responses as dependent variables. The particle size (PS) of 215.3 nm and maximum saturation solubility (SS) of 2805μg/ml was obtained as suggested solutions from factorial design which was further confirmed using check point analysis. Interaction of surfactant concentration and stirring time and their effect on particle size and saturation solubility was predicted using the contour plots and response surface plots. The optimized formulation showed around 99% metaxalone in vitro dissolution in comparison to around 46% dissolution from SKELAXIN® tablet at 30 minutes. These methodologies could therefore be employed successfully to improve solubility of any BCS class II drug and to predict effects and interactions of many experimental variables at the same time.

235-239

Authors: G. Prakash Williams1*, Anju Anand1, Parvathy A1, Rakky C. Raj1, Robert Raju1, S. Krishna Kumar2

Living organisms can be found over a wide range of extreme conditions. Most of the organisms living in extreme environments (i.e, extremophiles) belong to the prokaryotes. Halophiles are interesting class of extremophilic organisms that have adapted to harsh, hypersaline conditions. They are able to compete successfully for water and resist the denaturing effects of salts. The present study was an investigation on the in vitro antibacterial effect of secondary metabolites from halophilic bacteria isolated from salted fish samples. The cured salted fish samples were collected and enumerated using halophilic Nutrient Agar supplemented with 4% NaCl. The isolated and purified bacterial cultures are numbered as SF1, SF2, SF3, SF4 and SF5 are further identified using VITEK 2 system as Bacillus vallismortis, Ralstonia mannitolytica, Bacillus subtilis, Rhizoboum radiobacter and Kocuria kristina. Growth kinetics of halobacterial isolates were determined by spectrophotometric assay. The antibiotic resistance pattern of tested pathogenic microorganisms using the commercial antibiotics was screened and almost all the tested microorganisms are resistant to Penicillin. The antimicrobial activity of secondary metabolites of halophilic bacteria against drug resistant microbes was assessed using the Agar well diffusion assay. Among the different extracts of the halophilic bacteria, the chloroform extracts of R. mannitolytica showed maximum antibacterial activity against Bacillus subtilis MTCC 441 and Xanthomonas campestris MTCC 2286. The results of antimicrobial activity are considerable because it enables the identification of potential secondary metabolites present in marine halophilic bacteria, which act as source of innumerable therapeutic agents. Further research is highly warranted to find out the active principle responsible for the antibacterial property and to elucidate the structure of particular compound.