Abstract

The aim of this work was to investigate the effect of inhibition of CYP2C9 on the pharmacokinetics of glimepiride (GLM), with sulfamethoxazole (SMZ) as model inhibitor of CYP2C9 in vitro using human liver microsomes (HLM). The present study investigates and compares the impact of GLM as a substrate and SMZ as inhibitor on invitro kinetic parameters, namely Km, Vmax, IC50 and Ki. Attempts have also been made to quantitatively predict in vivo drug interactions in humans from in vitro data. The results indicate that, SMZ when used at concentrations lower than 500 μMole, can be used as selective inhibitor of CYP2C9 for in vitro studies. In this study, we systematically evaluated the inhibitory effects of SMZ on GLM metabolism mediated by CYP2C9. The predicted increase in plasma concentration of GLM is high, suggesting the risk of hypoglycemia when SMZ is coadministered with GLM.

Abstract

Quinoline, a heterocyclic scaffold which is well known for wide spectrum of biological activities.Quinoline-2-carboxylates with aromatic compounds and a terpene is synthesized under microwave which increased the yield and shortens the reaction time comparing to conventional method reported by us. The synthesized compounds are characterized by UV-vis, IR, NMR and mass spectra and other physico-chemical methods.The compounds were evaluated for their in-vitro antioxidant, antimicrobial and antiplatelet activities. The compound 3k(2-methoxyphenyl quinoline-2-carboxylate)and 3c (p-tolyl quinoline-2-carboxylate showed potential antioxidant activity evaluated by DDPH radical scavenging activity. Anti-oxidant activity of 3k is confirmed by liver microsomal lipid peroxidation inhibition.3a(2-isopropyl-4-methylcyclohexyl quinoline-2-carboxylate), 3f (4-chlorophenyl quinoline-2-carboxylate) and 3g (4-chloro-3-methylphenyl quinoline-2-carboxylate) showed significant anti-inflammatory activity. In anti-microbial studies the compounds 3i (3,4-dimethylphenyl quinoline-2-carboxylate) and 3j (3,5-dimethylphenyl quinoline-2-carboxylate) inhibited antimicrobial growth significantly where as3a and 3h(2,5-dimethylphenyl quinoline-2-carboxylate) inhibited moderately. Inhibition of fungal growth was effective by3c, 3a(phenyl quinoline-2-carboxylate), 3c, 3d (o-tolyl quinoline-2-carboxylate), 3e(m-tolyl quinoline-2-carboxylate) and 3f.3k is a potential anti-platelet agent where as 3c is a moderate one.

Abstract

Two-third of the world’s population lack essential mineral elements at all stages of life. Supplementation of these micronutrients during crop cultivation serves to be the ultimate goal of modern agriculture. Among the micronutrients, Selenium (Se) has been proved to be an essential element and has received considerable attention for its antioxidant activity, anticancer effect and other physiological functions. The Recommended Dietary Allowance (RDA) of selenium is 55- 200 μg/day for an adult. Agronomic fortification by foliar application was carried out to investigate the effects of selenium on growth, selenium accumulation, photosynthetic pigments, antioxidant activity and the micronutrients variations. Plants were grown in greenhouse condition amended with sodium selenate. Selenium enrichment enhanced the growth parameters and abridged the levels of chlorophyll at higher concentrations. The current results suggested the beneficial effects of Se on fenugreek growth and also its contribution to improve the nutritional value of fenugreek for human nutrition. To our best knowledge, this was the first report on selenium supplementation in fenugreek plant, which contains 29μg g-1DW; indicates intake of ~10-20 leaves /day will drive to maintain the regular selenium level. The biochemical characterization proved the nutritional quality enhancement by its increase in total phenolic and total protein contents. It indirectly indicates the increase in antioxidant enzyme production. Thus, selenium fortified fenugreek leaves can serve as a better nutraceutical food to improve the overall human health. In wrapping up, further studies are needed to assess the functionality of high-Se that measures changes in genome stability and immunocompetence.

Abstract

Ultra performance liquid chromatographic method was described for determination of Miconazole Nitrate and Betamthasone Valerate in bulk powder and in topical cream. The chromatographic separation was achieved on Kinetex core-shell C18 column (75x 2.5 mm, 1.8 μm). The separation is achieved applying a simple gradient program. The mobile phase contain a mixture of 0.05% orthophosphoric acid as aqueous solvent and acetonitrile as organic solvent in a gradient program was investigated to separate the drugs from their stressed degradation products. The flow rate was 1.3 ml min-1 and the column temperature was maintained at 40ºC. The detector wavelength was 230 nm. Miconazole Nitrate and Betamthasone Valerate were subjected to stress degradation conditions of hydrolysis (acid and base), oxidation and thermal degradation at 80°C for 1 hour. Stressed samples were analyzed by the developed procedures. The described method shows excellent linearity over a range of 20-300 μgml-1, 1-15 μgml-1 and determination coefficients were 0.9999 and 1 for Miconazole Nitrate and Betamthasone Valerate, respectively. Limits of detection were 0.77 and 0.34 μgml-1 and limits of quantification were 2.3 and 1 μgml-1 for Miconazole Nitrate and Betamthasone Valerate, respectively. Degradation of Miconazole Nitrate was observed in oxidative condition but found to be stable in other stress conditions while Betamthasone Valerate degradation was observed in acidic, alkaline and thermal conditions but found to be stable in oxidative degradation. This method capable of complete chromatographic separation of Miconazole Nitrate and Betamethasone Valerate peaks from their degradation product peaks generated under various stress conditions.

Abstract

Present work is to carry out an analytical method development of Gallic acid (GA) and Stigmasterol (STG) in pharmaceutical liquid dosage form of Maydis stigma (Corn silk). The developed method is based upon simultaneous equations method by using UV/Visible spectroscopy. The developed method can be used for the simultaneous estimation of GA and STG in pharmaceutical dosage form without separating from each other or from the excipients. Primarily the λmax of Gallic acid (GA) andStigmasterol (STG) was determined as 273 and 212 nm respectively. The suggested method is validated by using ICH validation parameters like accuracy, precession,linearity and LOD and LOQ respectively, Accuracy study showed percentage recovery in the range of 97-102% w/w respectively. Precision studies were carried out for 6 successive absorbance and studied for their percentage relative standard deviation (%RSD) was < 2%, LOD and LOQ was studied and the limit of detection and limit of quantification were found tobe was 1-100 μg/ml for Gallic acid and Stigmasterol, The slope of interpretation Y=0.0102+0.0692(R2=0.9891) and Y=0.0009+0.0322 (R2=0.9925) respectively. This procedure was applied successfully for analysis of GA and STG in pharmaceutical preparation of Maydis stigma (Corn silk) and this method can be used for analysis and routine quality control of herbal preparations containing Maydis stigma.

Abstract

Calcitonin Gene Related Peptide (CGRP) receptor has numerous implications on physiological processes in the body. Their effects range from vascular modulation to neurological disorders. Hence it’s always been a spotlighted target for many researchers working on these disorders. Even though it has crossed almost two decades since the importance of the receptor has been reported, not even a single drug molecule has made it to the market. Targeting the receptor using small molecule antagonists have proved to be unfruitful because of the receptor being a heterodimeric protein and the surface of the protein-protein interaction is large. However, most of the ligands developed and documented for this receptor have ignored some aspects of Lipinski’s rule of five especially with the molecular weight descriptor as small molecules are insufficiently fit inside the pocket leaving the key amino acids let loose. Even after compromising with several issues, hitting the ‘Hotspot’ proved to be easier said than done. Hence in this paper, we will study some aspects like how the receptor is formed and which protein-protein interactions result in the formation of CGRP as well as ‘CGRP like’ receptor using target identifying and bioinformatics’ online/offline tools and put forth a brief study on the receptor & the ‘Hotspots’ using the crystal structure of the protein and validating it using docking software. These observations might help to design a drug candidate with increased affinity, potency along with time and money factors which are important for drug discovery process. Overall, a comprehensive but concise research note on how to design some potential CGRP antagonists can be drawn as outcome from the current communication.

Abstract

Solid dispersions have attracted considerable interest as an efficient means of improving the dissolution rate and hence the bio availability of a range of poorly water-soluble drugs. The focus of one part of the review article is based on solid dispersion mainly advantages, disadvantages, types, the method of preparation, and characterization of the solid dispersion at laboratory and industrial level. Solid dispersion is basically a drug–polymer two-component system; the drug–polymer interaction is the determining factor in its design and performance. It also discusses about modern characterization technique to characterize solid dispersion. In this review, it is intended to discuss the recent advances related on the area of solid dispersion technology. Different methods are also been used for preparation of solid dispersions such as Melting method, Solvent method, Melting solvent method ,Melt extrusion method, Lyophilisation Technique, Melt Agglomeration Process, The Use Of Surfactant, Electro spinning and Super Critical Fluid (Scf) Technology. The introduction of fast dissolving dosage forms has solved some of the problems encountered in administration of drugs to the pediatric and elderly patient, which constitutes a large proportion of the world's population. Fast dissolving tablet containing solid dispersion was developed to improve the dissolution of drug and stability of solid dispersion. They are disintegrating and/or dissolve rapidly in the saliva without the need for water. Thus it is regarded as the safest, most convenient and most economical method of drug delivery having the highest patient compliance. The later part of the article focus on the progress in methods of manufacturing, evaluation and various latest technologies involved in the development of Fast dissolving tablets.

A novel validated HPLC method was developed for simultaneous determination of Ofloxacin and Ketorolac Tromethamine from bulk and eye drop formulation. This method is simple, precise, accurate and utilizes reverse phase SMT SAM-C18 column (4.6×250 mm) with a ternary mobile phase with pH adjustment to 2.7 with formic acid, at a flow rate of 1ml/min. Both drugs were qunatitated at 300 nm. The retention time for OFO and KTM was found to be 2.33 and 10.33 min respectively. Linearity was obtained in the concentration range of 3-90μg/ml of OFO and 5-150μg/ml of KTM with a correlation coefficient of 0.998 and 0.997 for OFO and KTM respectively. The percentage assay of OFO and KTM was found to be 98.82% and 98.42% respectively. The developed method was validated according to ICH guidelines and thus the proposed method can be successfully applied for simultaneous determination of OFO and KTM in routine analysis.

Abstract

Two simple, precise and accurate zero and first order derivative spectrophotometric methods were developed and validated for the determination of trimipramine in bulk and capsule dosage form. The quantitative determination of the drug was carried out using the zero order and first order derivative values were recorded at 251 nm and 218 nm respectively. The estimation of the drug was carried out by regression equations with standard solution. Calibration graph was found to be linear r2 = 0.998 for zero order and r2 = 0.997 for first order derivative over the concentration range of 800-2400 ng/mL. Precision study (intra-day relative standard deviation [RSD] and inter-day relative standard deviation RSD) values less than 2.0%, method is specific and robust. The % recoveries are ranging from 99.51-100.51% for zero order and 99.78- 100.39 % for first order method indicating that the methods were accurate. No obstruction was observed from general pharmaceutical excepients. The developed derivative methods can be utilized in its routine analysis trimipramine in quality control division.

Abstract

Two simple, precise, rapid and accurate methods for simultaneous determination of lamivudine (LAM), tenofovir (TEN) and nevirapine (NEV) in combined tablet dosage form are developed. Method A is based on ratio spectra derivative and method B is based on derivative spectra, methanol is used as solvent for both these method. Quantitation by ratio derivative amplitude was achieved at 352.9 nm, 359.9 nm and 348.9 nm for lamivudine, nevirapine and tenofovir, respectively for method A. Similarly the amplitudes at 324.01nm, 298.9 nm, 311.9 nm were measured for lamivudine, tenofovir and nevirapine for receptive drugs in method B. Beer’s law is obeyed in the range of 9-27 μg/ml by lamivudine, tenofovir and 6-18 μg/ml by nevirapine. The percentage assay in laboratory formulation was found to be in the range 99.39%100.23% by the proposed methods. The methods were validated with respect to precision, accuracy, specificity and robustness. The recovery was found in the range of 99.21-101.13 %. The methods developed are simple, economical, precise and accurate and can be used for routine quality control of analytes in combined tablets.

Abstract

Rapid and large scientific development of the heterocyclic compounds studied, whatever makes an order and requires research in methods of synthesis and study their properties. Increases the importance of this type of compounds every year, because of the many uses that are recognized and try to apply in the areas of human life cost to take advantage of them. Hence the interest in a comprehensive review of the procedures for studies and research that has been know about this type of compounds. Interest in studying and identifying characteristics have appeared in more than a hundred years. Exploit the properties and transformations that occur in these compounds makes them subject deserves, addition to the study of the interactions and logical access to new compounds suitable for use in the fields of medicine, pharmacy, agriculture and industry with the aim of all the service of humanity. The review of the literature shows that the benzimidazole derivatives are outstandingly effective compound and number of reviews available for biochemical and pharmacological studies conformed that their molecules are useful against a wide variety of microorganisms. Because of their importance, the methods for their synthesis have become a focus of synthetic organic chemists. Therefore in the present review tried to compile the chemistry of different derivatives of substituted benzimidazoles as well as various pharmacological activities and some of the important methodologies used for the synthesis. I hope that the benefit of all interested, researchers in this area and have this as a reference for those who want to learn more about this type of pleasant compounds .

Abstract

This paper presents the development of a new RP-HPLC method for the separation of lumefantrine and artemether in human plasma. Sample preparation involved the extraction using protein precipitation method with acetonitrile. Chromatography was performed with mobile phase containing a mixture of methanol and 0.025M ammonium acetate (38:52, v/v) with a flow rate of 1 ml min−1. Column effluent was monitored at 216 nm using a UV detector. The calibration graphs were linear in the range of 2.4-16.8 μg ml−1 for lumefantrine and 0.4-2.8 μg ml−1 for artemether with limits of quantification of 3.0 μg ml−1 and 0.6 μg ml−1 for lumefantrine and artemether respectively. Intra and inter-assay precision provided relative standard deviation lower than 10% for the analytes. Extraction recoveries of lumefantrine and artemether in plasma were 94.32-97.15% and 94.75-98.55% respectively. The proposed HPLC with UV detection is simple, rapid, precise and accurate. Therefore it is appropriate for the routine quantification of therapeutic levels of lumefantrine and artemether in human plasma.

Abstract

For the oral mucosal route of drug administration, various types of dosage forms can be prepared, such as adhesive tablets, adhesive gels, adhesive patches and many other dosage forms with various combinations of polymers, absorption enhancers. The duration of Sublingual Tablet delivery is short owing to the inevitable loss of a large proportion of the administered dose due to swallowing. To overcome such losses, a patch can be formulated that is located on the buccal mucosa of the oral cavity, i.e. buccal patches. The buccal region of the oral cavity is one of the beneficial routes of administration for systemic and local drug delivery, specifically in overcoming problems associated with the latter mode of administration, such as high first-pass metabolism and drug degradation in the G.I environment due to high acidic pH. The phenomenon of buccal drug delivery includes direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism which results in the increase of bioavailability. Moreover, rapid onset of action can be achieved relative to the oral route and the formulation can also be removed when therapy is discontinued. It is also possible to administer the drug to patients who are unconscious and less co-operative. Buccal mucosa has advantages like, rich blood flow, lesser thickness of the buccal mucosa and high permeability, low enzymatic activity in the buccal mucosa. In addition, studies have been conducted on the development of controlled or slow release delivery systems for systemic and local therapy of diseases in the oral cavity.

Abstract

In thepresentworkwehavedeveloped theSustain release tablet of acebrophylline& immediate release tablet of montelukast sodium were prepared by direct compression method, by using different concentration of sustain release polymer & immediate release polymer respectively.Bilayered sustain release tablet play an important role in improving the patient compliance and reduce frequency of dosage form taken by a patient. The main objective of formulating this bilayer tablet for treatment of chronic obstructive pulmonary disease(asthma and allergic rhinitis &anti-inflammatory action) and decreases the frequency of administration of dosage form and improves the patient compliance. As a part of characterization studies of Acebrophylline&montelukast sodium, Differential scanning calorimetry (DSC) was used to investigate thermal effects and nature of drug, High performance liquid chromatography method was used for identification, assay of pure drug and in-vitro drug release studies of different trials, Compatibility was done by FTIR interpretation & physical compatability method. For sustain release tablet of acebrophylline, formulations was prepared in which (25% guar gum with 30 % HPMC K100) was the best formulation and gave better drug release. For immediate release tablet of montelukast sodium formulations was prepared in which (3% Crospovidone XL-10) was the best formulation and gave better drug release.

Abstract

The purpose of this study was to evaluate the prevalence of self-medication practice and to create awareness for misuse of antibiotics among health care professional in Uttar Pradesh, India. It’s a cross-sectional study design which attempts to measure the self-medication practices among the health care professional through questionnaire based study. Among 300 participant’s, 266 (88.6%) were practicing self medication. The reason among those who did not practice self-medication was awareness for adverse reactions and misuse of antibiotics. Self-medication practice was more among physician (86%) followed by pharmacist and nursing staff (70%), dentistry (49%) and physiotherapist (38%). A majority, 97 (36.47 %), of the health care professionals used antibiotics for fever followed by Diarrhea (13.16%), Sore throat (7.14%), Common cold (7.14%), Pyorrhea (3.38%), UTI (9.02%), Peptic ulcer (5.63%), Wounds (10.90%), Conjunctivitis (3%), Skin infection (4.13%). Sources of drugs for self medication were medicines store (71%), community pharmacies (29 %). The prevalence of the practice of self-medication was highest among the age group of 31 – 40 years but lower in the 51 - 60 and > 61 years of age groups, respectively. Males exhibited higher prevalence of self-medication than females. In our study self-medication was more among graduates followed by diploma and postgraduates. This study shows the need to aware health care professional about the use of antibiotics. Hence it is needed for health care professionals, specially physicians, dentistry, physiotherapist, nursing staff and pharmacist to participate for creating awareness for the use of antibiotics, besides help from the pharmaceutical industry, government regulatory bodies and continuous inspection by the relevant authorities. The study revealed that the prevalence of self-medication with antibiotics by health care Professionals in Uttar Pradesh is very high. It is although difficult to eliminate, effort can be made to discourage this practice and ensure safer usage of antibiotics which will require better education of health care professionals to avoid the irrational use of antibiotics.

Abstract

Presented study was an initial attempt to discover bergenin as an antiemetic compound isolated from Peltophorum roxburghii L., leaves. It is the extension of antiemetic activity from methanol extract of Peltophorum roxburghii L., leaves. Antiemetic activity was assessed using copper sulfate induced emesis in chick’s model. Bergenin (25 mg/kg, p.o.) exhibited significant antiemetic activity when compare with standard drug, chlorpromazine. This is the first time that, bergenin declares antiemetic activity. Bergenin has already been evaluated positively for its anti-inflammatory activity and now this paper going to report its antiemetic activity. Both the activities of same compound may be beneficial for drug designing against the disease having anti-inflammatory and antiemetic both symptoms just like migraine. The preliminary antiemetic evaluation of bergenin was conducted on single dose due to the low yield of Bergenin. However the result was significant with reference to the standard used. Further, isolation and purification of Bergenin is in process to establish a detail data on having different doses of Bergenin.

Abstract

Targeted drug delivery, sometimes called smart drug delivery which can deliver the drug to specific site of the body. Hydrocolloids based polymeric materials represents one of the most rapidly advancing research areas and established itself as an integral part of targeted drug delivery systems. This review focused the development of hydrocolloids particularly on targeted drug delivery applications such as oral delivery, ocular delivery, chrono drug delivery etc. The application of hydrocolloids mainly drug delivery system based on properties of polymeric materials that are used in the pharmaceutical field.

Abstract

The objective of the present research work was to develop immediate release tablets of ofloxacin in order to achieve rapid release in GIT which may result in enhanced absorption and thereby improved bioavailability. Immediate release tablets comprising solid dispersion of Ofloxacin as main constituent in six trial batches using crospovidone & sodium CMC as superdisintegrants in different ratios along with other excipients. The different batches were evaluated on the basis of disintegration time and invitro drug release. The best batch (T3) containing crospovidone was selected as a source of information for designing factorial batches. The best batch consisted of crospovidone (9 mg) which was used as a source of information to prepare factorial batches of immediate release tablets.All the batches of immediate release tablets were evaluated for pre-compression parameters such as bulk density (0.659-0.686 gm/cc), tap density (0.696- 0.737 gm/cc), hausner‟s ratio (1.05-1.08 ), angle of repose ( 25.33-28.300, carr‟s index ( 5.38-7.98 ) & post-compression parameters like hardness ( 3.0 – 7.0 Kg/cm2), thickness ( 3.50-3.62), weight variation (Passed), disintegration time ( 17.3-193.3sec) and in-vitro drug release determination ( 100.50%). The results of accelerated stability studies revealed no physical and chemical changes in the tablets during three months of experiments.Final batches were prepared based on 32 factorial design with different concentrations of crospovidone (5, 7 & 9 mg) and varying hardness (3, 5 &7 kg/cm2) as two independent formulation variables. Two dependent response variables considered were disintegration time and percentage invitro drug release. The desirability fraction was used to optimize the response variables each having different targets i.e. minimal disintegration time & maximal dissolution, and the observed responses were agreeable with experimental values.

 Abstract

Precondylar tubercles are occasional, single or paired osseous structures seen on basion, anterior to foramen magnum. The presence of precondylar tubercle has clinical relevance in radiology, orthopaedics and neuro-surgeries. We examined 75 dried adult human skulls for the possibility of precondylar tubercle and observed its morphology, location and incidence. The precondylar tubercle was observed in 5 specimens (6.7%) with varied morphologies, like ridges, spines and process. The present study addresses the incidence, presentations, embryological basis and clinical significance of precondylar tubercles in adult human skulls of Indian origin.

Abstract

Problems regarding effective and convenient delivery of drugs to brain are larger as there are large number of barriers to brain and limited vascular access of brain. Many advances are been made in recent years to deliver drugs to brain. Intranasal drug targeting is one of these approaches. It is convenient and easily accessible. Also a desired drug candidate for brain targeting with poor aqueous solubility and high lipophillicity can be formulated into nanosuspension so the intranasal delivery can be convenient and simple. A novel approach to deliver drugs to brain can be in form of nanosuspension. The nanosuspension surpasses the BBB as size range is 1-1000nm. As compared to conventional formulations, nanosuspension serves a promising approach in drug targeting to required organ.

Abstract

Four plants viz. Withania somnifera, Boerhaavia diffusa, Tinospora cordifolia, and Stevia rebaudiana were evaluated for their -amylase inhibitory potentials. Total 10 g root powder of Withania somnifera and Boerhaavia diffusa, 10g of stem powder of Tinospora cordifolia, and 10.0 g leaf powder of Stevia rebaudiana were extracted in hot distilled water and ethyl alcohol. Extracts were condensed in rotary evaporator and dried in oven at 45-50 oC. Hot water extraction method produced more extractives when compared to ethanol extraction method. Dried extractive from each plant was dissolved in distilled water and used for human salivary -amylase (HSA) and porcine pancreatic - amylase (PPA) inhibitory assays. Water extracts of W. somnifera, T. cordifolia and S. rebaudiana showed more inhibition - amylases as compared to ethanol extracts. However, in case of B. diffusa ethanol extract exhibited significantly more inhibitory action on HSA and PPA as compared to water extract. Among four plants W. somnifera water extractive exhibited maximum -amylase activity, was followed by T. cordifolia and B. diffusa; whereas S. rebaudiana showed comparatively lower inhibitory activities for the said enzymes. Extractives of all four plants showed more inhibition of HSA than PPA in in-vitro assay conditions. HSA and PPA inhibition activities of selected plants may be due to presence of phenolics, flavonoids and saponins in plant extracts, however further detailed scientific investigations are essential to confirm these claims.

Abstract

A series of S,S-bis substituted benzyl derivatives with Nitroketene dithioacetal motif are synthesized using a two-step process starting from the condensation of Nitromethane (1) with carbondisulfide (2) in presence of dry methanolic potassium hydroxide to form dipotassium salt of Nitroketene dithioacetal (3) in the first step and which upon further treatment with appropriate substituted benzyl bromides in a bifacial immiscible solvent system of dichloromethane and distilled water assisted with tetra-n-butyl ammonium bromide (TBAB) as phase transfer catalyst to yield S,S-bis substituted benzyl derivatives with Nitroketene dithioacetal motif (4a-h). The structures of the synthesized products were characterized using UV, IR, 1HNMR,13CNMR and LC-MS and C,H,N elemental analytical evidences. The synthesized compounds 4a-4h were screened for anti-bacterial activity using disc diffusion method and Central nervous system activity screening using Albino mice animal screening model. The products 4b and 4f showed potent antibacterial activity against tested gram-ve organism compare to the standard drug sulphadiazine. The products 4e showed potent antibacterial activity against tested gram+ve organism. The product 4e showed potent CNS depressant activity than the standard drug chlorpromazine and the remaining products showed good CNS activity compare to the standard drug.

Abstract

Prior to conduct of any clinical trial on human volunteers for any new investigational product (IP), there are specific regulatory requirements which are required to be fulfilled by the investigator and sponsor. An investigational new drug (IND) application should be filed with the Food and Drug Administration (FDA). It can be exempted, if it meets specific criteria of exemtion from IND. The filing of an IND mainly involves 3 parts viz., FDA form 1571, FDA form 1572, and FDA form 3674. After getting approval from FDA, the clinical study may be proceeded after 30 days. The study may not be started if it is on “clinical hold” or any further information is required by the FDA. This review article addresses briefly the process of filing an IND application.

Abstract

Vicinal halohydrins are important and versatile synthetic intermediates in the synthesis of wide range of biologically active natural and synthetic products. Although there are very few reports on ionic liquid (IL) mediated regioselective ring opening of epoxides to halohydrins, limited to utilization of large amount of expensive ILs and longer reaction time. In the present methodology Lewis acidic IL, choline chloride.2ZnCl2 has been explored for the first time as catalyst as well as chlorinating agent for the formation of vicinal-chlorohydrins from epoxides. The protocol is mild, efficient, regioselective and insensitive to many acid sensitive protecting groups. IL reported here is cheap, easy to prepare and required lower amounts (0.25 molar equivalents to the substrate) compared to imidazolium based ILs.

Abstract

The aim of this study is to formulate and characterize Rosuvastatin loaded Chitosan nanoparticles prepared by ionic-gelation method. Rosuvastatin Calcium has a low bioavailability (20%) due to poor absorption of the drug. Chitosan is a polymer of linear polysaccharide, which enhances transport of drug across epithelial surfaces and is biocompatible and biodegradable. The nanoparticles obtained were evaluated for percentage yield of drug, drug entrapment efficiency, particle size and morphology using Scanning Electron Microscopy (SEM), compatibility studies using Fourier-Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) and in vitro release kinetics. Among the four different drug to polymer ratios, 1:1 ratio showed high encapsulation efficiency and drug loading. The nanoparticles obtained were spherical in shape with a smooth surface with particle size range between 231.52 ± 24.12 nm to 405.25 ± 17.42 nm. The nanoparticles prepared proved to be a promising dosage form of Rosuvastatin, with improved bioavailability.

 Abstract

The aim was to develop the medicated lipstick using natural ingredients. The drug used in the formulation is Terbinafine hydrochloride which is used for anti-fungal therapy. Preformulation studies revealed that API and excipients were found to be compatible. For the formulation of lipstick Box-Behnken design was used. Three factors three level design selected on the basis of preliminary trials. Three independent factors like concentration of bees wax, concentration of carnuba wax and Concentration of Isopropyl myristate were selected. Quadratic model was selected for the prediction of the responses of dependent variables such as hardness (R1) and drug release (R2). Response surface plots were drawn to find out the optimized formulation. Evaluation test like breaking load test, softening point, permiability, melting point and antifungal activity was performed on the finalized formulation.

 Abstract

During antidandruff activity of various aromatic plant oils viz., Syzygium aromaticum (PCL 000201337), Foeniculum vulgare (PCL 00201338, Trachyspermum ammi (PCL 00201339), the essential oil of Syzygium aromaticum was found to be the most potent antidandruff agent, inhibiting the mycelial growth of test pathogens viz., Malassezia furfur (MTCC 1374) and Malassezia pachydermitis (MTCC 1369) completely. The MIC of the oil was found 0.312 l/ml concentration inhibited the tested pathogens while at 0.625 l/ml showed fungicidal concentration. Oil also found to be thermostable up to 1000C and did not expired upto 48 month of storage. The gas liquid chromatographic (GLC) analysis of the oil indicated it to be a mixture of 1 major (eugenol) and 25 minor components. The oil was found many time more effective in comparison to synthetics drugs, itraconazole and fluconazole. Thus, the essential can be recommended for safe, thermostable and long duration effects without any adverse effect and could be used as potential natural remedy after undergoing successful in vivo trials.

Abstract

Heavy metals including cadmium, mercury, lead, aluminum, arsenic and many more always remain a serious threat to human health but despite of this fact their use is still continuous. Various cadmium compounds are used in different products of daily use like cadmium compounds in PVC products (as stabilizers), color pigments, several alloys etc. Different waste as well as useful materials like phosphate fertilizers to farmland are causing the contamination of soils with cadmium. As a result of this cadmium contamination there is an increase uptake of cadmium by plants (Fruits and vegetables etc) used by humans. Furthermore sewage sludge to farmland and low pH of soils enhances uptake of cadmium by soils ultimately increasing cadmium load of crops and vegetables. Cadmium affects/damages kidneys resulting dysfunction of tubules of kidneys. By using Ellman’s modified method the interaction of CNT (Cadmium Nitrate Tetrahydrate ) with human cytosolic-GSH and plasma-GSH was studied. It was recorded that cadmium nitrate tetrahydrate continuously depleted the plasma-GSH level as well as cytosolic-GSH level by its different concentrations and with the increase of incubation time which was probably due to oxidation of Glutathione (GSH) to its corresponding disulphide (GSSG) form or by GS-Cd-SG conjugate formation.

Abstract

Over the last decades pregnancy related mortality has been increased. Approximately 1-4% of the pregnancies can be complicated by cardiovascular diseases. Approximately 10-25% of the maternal deaths were due to maternal cardiac complications. At present, advancements in health care services allowed the health care professionals to detect the cardiovascular complications in pregnant. Initial discovery of cardiac disease can be achieved by complete assessment of the patient throughout the pregnancy period. The present study was a retrospective cross-sectional study, conducted at Konaseema Institute of Medical Sciences and Research foundation (KIMS&RF), Amalapuram, Andhra Pradesh, India. This study was carried out for a period of six months which was previously approved by the institutional ethics committee. Past six years Case records of Obstetrics and Gynaecology department were subjected for screening from the medical records section. Patients were categorized based on the New York Heart Association (NYHA) classification. In this study, a total of 12,719 pregnant cases were screened to detect the cardiac complications in pregnancy. Among these cases, 50 cases were observed with cardiac diseases and the prevalence of cardiac diseases among the pregnant women was found to be 0.39%. Majority of the cases were found to be between the ages of 21-25 years. In our study, mean age was found to be 26 years. Rheumatic heart disease is the most common cardiac complication observed. About 32 % of cases were associated with obstetric disorders. Cardiologist and gynecologist should be aware of the cardiovascular complications during pregnancy. It is very important to counsel the patients prior to the pregnancy regarding the potential complications associated with maternal cardiovascular diseases. A female patient with known cardiac disease should consult a physician before becoming pregnant. A team work should be very much essential to carry out the management that includes obstetrician, cardiologist and anesthesiologist. In our study, no pregnant was dead due to their cardiac complication during their pregnancy. Mortality due to cardiac disease can be prevented is largely dependent on timely interference. Despite low maternal and neonatal mortality, pregnancy in women with cardiac disease is associated with significant cardiac and neonatal morbidity. Hence, it is the responsibility of all the health care professionals to involve completely for providing an effective patient care for the pregnant women with cardiac disease.

Abstract

Ethanol and chloroform extracts of four Indian medicinal plants were subjected to analysis of antioxidant activity. Plants used for analysis are Grewia asiatica L., Caesalpinia bonducella L., Syzigium samarangense (Blume), Asteracantha lonfigolia L. The assays employed for the analysis were reducing power assay and scavenging effects on DPPH radical, hydroxyl radical, hydrogen peroxide radical, nitric oxide radical. The results obtained indicate that the antioxidant potential varied significantly from plant to plant and extract to extract. Concentrations at 50% inhibition (IC50 values) were obtained for each extract in all performed assays. The total phenolic contents of plant extracts were determined using Folin-Ciocalteu reagent. From the results, seeds of A. longifolia were found to possess good antioxidant activity amongst four medicinal plants.

Abstract

We sought to examine the comparative improvement in health status and clinical outcomes in patients undergoing primary mitral valve repair versus replacement with mitral valve disease (mitral stenosis or mitral regurgitation). We prospectively followed 44 patients with mitral valve regurgitation and stenosis who underwent primary mitral valve repair (n =15) and replacement (n =29) between January 2013 and March 2013. Health status was evaluated at baseline and 1, 3, and 6 months after surgery with the validated short-form 36, Echo parameters, anticoagulation management and from the sf-36, utility scores and Quality adjusted life years was calculated Quality of life scores were significantly improved after both procedures, with better improvement achieved by mitral valve repair (P < .05). For both treatment groups, scores for most of the short-form 36 domains were depressed at 1 month; however, after 3 and 6-month lags, dramatic improvements were achieved in most of the domains. For patients, who underwent repair showed significant improvement in 3 and 6_month particularly physical functioning, mental health. Clinical parameters like Ejection Fraction showed improvement in both groups with minimal difference. The Adverse drug reactions observed in replacement due to life time anticoagulation therapy are found to decrease quality of life scores (average=2.3). Utility, which is obtained from quality of life scores were also showed to be better in patients who underwent mitral valve repair (0.82) and mitral valve replacement (0.69). Our study suggests that after mitral valve surgery, there is significant improvement in health status (quality of life) and number of quality adjusted life years (QALY) gained, especially in patients undergone mitral valve repair, when compared to patients undergone mitral valve replacement.

Abstract

The objective of the study was to develop and validate the in vitro in vivo correlation models of Ondansetron hydrochloride sustained release tablet. In-vitro test was examined by using the USP XXIII dissolution apparatus (type II, paddle) at 50 and 75 rpm and media used was pH 1.2, 4.5, 5.5, 6.8 and 7.2 buffers. The f2 similarity factor was used to evaluate the In vitro data. Three-way crossover bioavailability study was conducted in six healthy subjects. Pharmacokinetic data were calculated by using non compartment model. The best discrimination was achieved at pH 4.5 buffer at 50 rpm therefore selected as the choice of medium. The formulations were compared using time to reach peak plasma concentration and area under the plasma concentration–time curve while correlation was determined between in-vitro release and in-vivo absorption. An average prediction error for (peak plasma concentration) Cmax was 8.70% and -7.91% for fast and slow release formulation whereas for (area under the plasma concentration curve) AUC it was 9.27% and 8.44% for fast and slow release formulation. The low prediction error of Cmax and AUC shows that IVIVC (in vitro in vivo correlation) model is valid. This study point towards that developed dissolution tests can be used as a surrogate for bioequivalence studies, process development for final products, to ensure batch to batch bioequivalence.

Abstract

BACKGROUND:Osteoporosis is a disease characterized by low bone mass and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. It is the most common metabolic bone disease and can result in devastating physical, psychosocial, and economic consequences. It is often overlooked and undertreated, however, in large part because it is so often clinically silent before manifesting in the form of fracture. METHODOLOGY: It is a cross-sectional study involving 600 subjects. The knowledge, attitude and practices (KAP) were assessed along with the risk factors which includes modifiable and non-modifiable risk factors based on OPQ questionnaire and IOF(international osteoporosis foundation)one minute risk test. The quality of life of the subjects was obtained using a IOF Quality of life questionnaire (QUALEFFO-41).Counseling was provided to the subjects regarding the disease, its risk factors and lifestyle modifications which includes diet and exercise to be followed. The subjects at risk were detected by evaluating the questionnaires. A follow up study was conducted for 153 people who are at high risk osteoporotic people to study the impact of pharmacist counseling on the modifiable risk factors and their KAP levels. RESULTS: The study involved 602 women above 25 years of age of which 100 (17%) women were having medical conditions which expose them to osteoporosis risk. Remaining 502 (83%) women were not having any medical conditions. Their knowledge, attitudes and practices towards osteoporosis was evaluated and it was found that above 85% women were at poor knowledge about the disease and its risk factors. Average modifiable risk was found to be 4.6 (1.23) and average non modifiable risk was found to be in a range of 2-4. The study included 32 already diagnosed osteoporotic women who were on medications. IOF one minute risk was assessed for 602 women and found out that 120 members(20%) were at high risk. Quality of life was assessed for women who were osteoporotic (5.31%) and women at high risk (20%). It was observed that there was no much significant differences in the majority of the domains of quality of life. CONCLUSION: The IOF one minute risk test and OPQ questionnaire are useful tools in assessing the risk and the KAP of the subjects and predicting the subjects at high risk. By pharmacist counseling the subjects were able to improve the KAP on Osteoporosis and depreciate the modifiable risk factors and adapt life style modifications for prevention of the osteoporosis.

Abstract

Cancer is an important area of interest in the life sciences because it has been a major killer disease throughout human history. Pyrrolopyrimidines are well known to play a critical role in health care and pharmaceutical drug design. Currently a number of Pyrrolopyrimidines are available commercially as anticancer drugs and great efforts have been put to the identification of novel anticancer targets for novel anticancer drug discovery. The focus of this review is to provide a comprehensive and up-to-date account on the most recent development in the medicinal chemistry of pyrrolo[2,3-d]pyrimidine derivatives with significant anticancer activity starting from the last exhaustive publication in this field.

Abstract

In DNA vaccines the foreign DNA is used to express an encoded protein & fuel the body’s immune system. It represents a new approach to immunization which is potentially less exclusive than the older vaccines. After inoculation into the host, DNA enters the cells, where the antigen is expressed, processed & then predictable by immune system as in a natural infection. Certain methods like gene gun & electroporation are used to deliver DNA vaccines.DNA vaccines undergo through clinical trials to find the way to treat autoimmune diseases, hepatitis, mycobacterium diseases, allergy & malaria. This review focuses on mechanism by which DNA vaccination induce immune response, delivering method & applications of DNA vaccinations.

Abstract

The aim of this study was to investigate the possibility of enhancement of aripiprazole dissolution by solid dispersion technique. Solid dispersions (SDs) of aripiprazole were prepared by solvent evaporation technique using various polymeric drug carriers like Hydroxy propyl methyl cellulose (HPMC), Polyethylene glycol (PEG), Poly vinyl pyrolidone (PVP), Croscarmellose sodium (CCS), Sodium starch glycolate (SSG) and Crospovidone (CP) and characterized for DSC, FTIR and the dissolution studies. Based on the dissolution study, SD1 and SD3 (at 10 min, 76.92 + 0.18% and 69.98 + 0.25%) showed fast and higher dissolution rate when compared to other solid dispersions and pure drug (at 30 min is 21.77 + 0.21%). These SD1 and SD3 formulations were further developed as SD7-SD10 by altering their drug, carrier ratios and observed for its drug release studies, where again SD1 and SD3 has shown higher drug release than SD7-SD10. Based on the dissolution study, SD1 and SD3 were selected for the formulation of fast dispersing tablets and evaluated for hardness, friability, weight variation and drug content. From the tablet formulations, F1 and F2 showed rapid and higher dissolution rate than others formulations and pure drug (D). F1 and F2 showed fastest disintegration time (5 sec and 6 sec) than other formulations due to use of crospovidone as superdisintegrant in these tablets absorbs a huge amount of water. The FTIR and DSC studies showed the absence of interaction between aripiprazole and CCS/CP carriers. Hence, it can be concluded that solid dispersions in association with superdisintegrants showed marked improvement in the dissolution rate of aripiprazole using solvent evaporation method.

Abstract

In the present investigation, a series of novel 3-(4-substituted-phenyl)-9-methyl-thieno[3,2-e] [1,2,4]triazolo[4,3-c]pyrimidine-8-carboxylic acid (4-substituted-benzylidene)-hydrazide (5a-o) were synthesized and developed as better antimicrobial agents. The chemical structure of the newly synthesized compounds were characterized by spectral (IR, 1H NMR, 13C NMR, LC-MS and CHN analysis) methods. It was observed that the compounds with chloro substituted thieno[1,2,4]triazolopyrimidine showed better antimicrobial activity. The compound (5a) showed significant antibacterial activity against B. subtilis with MIC 1.56 μg/mL and antifungal activity against A. niger with MIC 1.56 μg/mL as compared to the standard drugs. Herein we wish to report the synthesis and antibacterial efficacy of a new series of 1,2,4-triazole and Schiff’s bases bearing thienopyrimidine moiety (5a-o).

Abstract

A simple, selective, linear, precise, and accurate RP-HPLC method was developed and validated for the simultaneous estimation of Metformin and Telmisartan from bulk and formulations. Chromatographic separation was achieved isocratically on a Waters C18 column (250×4.6 mm, 5 μ particle size) using a mobile phase, (Mixed Phosphate buffer pH adjusted to 3.0 with orthophosphoric acid& acetonitrile in the ratio of 50:50 v/v. The flow rate was 1 ml/min and effluent was detected at 234 nm and 10μl of sample was injected. The retention time of Metformin and Telmisartan were 2.257 and 5.790 min respectively. Linearity was observed in the concentration range of 30-90 μg/ml for Metformin and 2.4-7.2 μg/ml for Telmisartan. Percent recoveries obtained for both the drugs were 98-101%and99-100 respectively. The percentage RSD for precision and accuracy of the method was found to be less than 2%. The method was validated according to the ICH guidelines with respect to specificity, linearity, accuracy, precision, LOD and LOQ. The method developed was successfully applied for the analysis of simultaneous estimation of Metformin and Telmisartan tablets.

Abstract

Cancer can be described as the uncontrolled growth of abnormal cells. Protein Kinase plays major role in cells signaling to undergo many cellular functions. Many targets for the treatment of cancer cells are available namely stem cells, protein coupled receptors, ErbB receptor, steroid hormones proteases, vascular endothelial growth factors, chemokine receptors and reverse transcriptase/ ribonuclease. The protein-ligand interactions play a significant role in structural based drug designing. In our present research work we have chosen protease, reverse transcriptase and endothelial growth factor as targets to screen our proposed chemical structures for anti-cancer activity. The molecules were docked to the above said targets and the energy values obtained are as follows. Using the docking software. Depending on the energy values we have choosen the best two drug analogs they are Compound C26{ -11.3}, Compound C38 { -9.7} .We tried to improve the binding efficiency and steric compatibility. Several modifications were made to the probable functional groups which are interacting with receptor molecules. Analogs of this drug molecule were prepared using ACD-chem.-sketch and docking. The modified drugs was sketched using chem.-sketch were found to be better than the conventional drugs available.

Abstract

New drug discovery is considered broadly in terms of two kinds of investigational activities such as exploration and exploitation. Docking of small molecules in the receptor binding site is a vital part of structure based drug design. The current study deals with the evaluation of chalcone derivatives with various targets of Mycobacterium, Cancer and anti-oxidant using in-silico docking studies. In this perspective, chalcone derivatives like peroxide derivatives and nitropropane derivatives are docked with targets like 1z5v (Tubulin gamma-1-chain), 1yfz (Hypoxanthine-guanine phosphoribosyl transferase), 1pxx (Prostaglandin G/H Synthase 2), Protease (1a30), Reverse Transcriptase (1cot), Vascular Endothelial Cells Growth factor receptor (1y6a). In-silico docking studies were carried out using mcule online docking. OSIRIS property explorer used to explore the molecular properties. Metabolic sites are predicted using metaprint2D.

 Abstract

In the present investigation was aimed to isolate and identification of bioactive compound from Crotalaria pallida endophytic fungal Alternaria species ethanol extract and evaluated for in vitro cytotoxicity assays using onion roots, yeast and greengram germination method. MAE method was used for isolation of potent compound and subjected to purification from HPLC with standard compounds. In vitro cytotoxicity methods were used to know the toxicity level of the isolated compound. MAE method yielded major bioactive compounds along with three coumarin(s) and it was confirmed with all four tests and the 5th test confirmed as a phenolic agent. Endophytic fungal coumarin inhibited the actively growing onion root meristematic cells by possessing various abnormalities by producing highest percentage of cytotoxicity (18.05%), the death of yeast was observed in extract treated yeasts and the percentage of toxicity was 88.03% and at 400 μL of endophytic coumarin inhibited the greengram germination and there is no germination was observed. The fungal coumarin also cleaved the DNA in yeast and it is a strong evidence of toxicity in DNA level and shown apoptosis activity. For all experiments, standard coumarin was used. The endophytic fungal coumarin results were near to equal of standard. From the obtained results, the endophytic fungi Alternaria species have the ability to produce coumarin and it exhibited as strong in vitro cytotoxicity activity. It can be used as a cancer drug after test against cancer cell lines.

Abstract

Methanol extracts of Cassia fistula was used for phytochemical analysis and totally 10 different phytoconstituents were identified from GC-MS. Two compounds (citronellol and linoleic acid) out of ten have already shown as anticancer agents. In MTT assay, in 30 μg treated human cancer cells showed less viability (5.06%). If the concentration of extract decreases the viability was less reason is that drug dose dependent. The anticancer activity was observed in extract treated cancer cells by Acridine orange assay, observed the necrosis and arrested the cell cycle at different stages. The extract induced the activities of caspase -3, 7, 9 and 10, these enzymes are crucial for apoptosis and they are quantified and compared with untreated control. The activity of these enzymes was increased from 2 fold to 5 fold. The genomic DNA fragmentation was observed in extract treated cancer cells. We conclude that the methanol extract of C.fistula having anticancer agents and they showed anticancer property in MTT assay confirmed by acridine orange test. The extract inhibited the cell growth and induced the cell death by modulating caspase enzymes and cleaving genomic DNA. Further work is needed to identify the exact anticancer agent in methanol extract of C. fistula.

Abstract

Mental illnesses are medical conditions that disrupt a person’s thinking, feeling ability to relate to others and daily functioning. Anti-psychotic medications are available in India since a long time. These drugs are capable of causing a number of ADR some of which may be fatal. Also polypharmacy is one of the leading cause of ADR in psychiatry patients. Thus our aim was to evaluate the demographic factors and drug utilization pattern in psychiatric illness patients. It is a questionnaire based prospective-observational study. This study included hospital out-patients treated in psychiatric department. Data was collected from the medical records of out-patients and patient interviews. The diagnosis was made according to DSM-IV criteria. A total of 201 patients were enrolled in the study, 65.2% patients belongs to age group of 18-40 years; male patients were more in number. In patients history, it was revealed that family problems and trauma were the main reasons for their present illness; also some childhood neurotic traits was assessed in patients. 77 patients were diagnosed with Mood disorders and 74 patients were diagnosed with Anxiety disorders. Out of 435 drugs prescribed, 145 drugs are anti-depressants, 97 anxiolytics, 87 antipsychotics, 16 anti-cholinergics and 32 anti-manic drugs. In the study, two drug regimen was used more commonly. Thus the study should be conducted in a large number of patients as it can assess more risk factors, their pre-morbid conditions and childhood neurotic traits. Also it can assess the therapy which helps to know the rationality.

Abstract

Epilepsy, a chronic condition defined as two or more recurrent, unprovoked seizures, which has the highest incidence at the end of life. Antiepileptic drugs (AEDs) are primary therapeutic mode for epilepsy. AED treatment has been demonstrated to control seizure, which decreases morbidity and mortality associated with epilepsy. Nevertheless, the risks of significant adverse effects and drug interaction increase when more than one drug is used. Hence, drug use evaluation (DUE) programs play a key role in helping managed health care systems understand, interpret, and improve the prescribing, administration, and use of AEDs.The purpose of this study was to evaluate use of antiepileptic drugs in epilepsyOutpatient Clinic of Bishoftu General Hospital (BGH), East Shewa, Ethiopia.A retrospective cross-sectional study was applied and all the necessary data was collected from the epileptic patient cards using the pre-developed data collection format. The data collection was conducted from March 10 to April 10, 2014.A total of 259 patients’ information cards which contain AEDs were studied. Among them 135 were males and 124 were females. Out of total 15, 65, 172 and 7 of the patients were in the age group of < 5, 5-18, 19-65 and > 65years, respectively. Generalized tonic-clonic (48.6%) were the most common type of epileptic seizure seen. Monotherapy (88%) was most frequently used. Headache (47.8%) was the commonest adverse effect complained by the patients. The most commonly prescribed AED was phenobarbitone (92.8%), followed by Phenytoin (3.8%). Fifty four percent (54.4%) of AED use was in accordance with the indication set in the national standard treatment guideline while 2.9% were inappropriate. Also, 121(44%) of the indications were found to be difficult to know whether they are correct or incorrect indications since the type of epilepsy was not identified & written on the patient card. There were 16.5% under dose, 1.1% over dose and 12.7% AED use was with incorrect duration. There were potential drug-drug interactions in 5%. The present study has attempted to reveal the practical use of AEDs in epilepsy Outpatient Clinic of Bishoftu General Hospital (BGH), East Shewa, Ethiopia. Consequently, the classification of seizure as well as the use of drugs with potential drug interaction, dose and duration problem needs urgent interventions.

Abstract

In this work six 3-aryl-2-(substitutedstyryl)-4(3H)-quinazolinones derivatives were synthesized by the reaction of 3-aryl-2-methyl-4(3H)-quinazolinone (intermediate products) with different substituted aromatic aldehydes. Three intermediate products were synthesized by reacting 2-methyl-3, 1-benzoxazin-4-one, which was initially prepared by cyclizing anthranilic acid using acetic anhydride, with three aromatic amines. Their structures were confirmed using IR, 1HNMR, 13CNMR spectroscopic methods and elemental microanalyses. The synthesized compounds were evaluated for their in vivo antimalarial activity against P. berghei. Four of the synthesized compounds (IIIc, IVa, IVb and IVf) exhibited activity against the parasite. Among these compound IVa was found to be the most active compound. Results of acute toxicity study showed that oral administration of the synthesized compounds in single doses (100, 250 and 500mg/kg) had no adverse effects, indicating that the compounds have high safety margin and their LD50 is higher than 500 mg/kg. In general this study indicates that 4(3H)-quinazolinones derivatives are potential sources of lead compounds for antimalarial drugs.

Abstract

Non steroidal Anti- inflammatory drugs have their origin as the derivatives of plants, which were observed to have their therapeutic effects in different disease states. Topical delivery of NSAID has its therapeutic applications in management of pain and inflammation in Rheumatoid arthritis patients. The aim of the present investigation was to compare the Etoricoxib cream with Diclofenac and Piroxicam cream in a group of volunteers suffered from Rheumatoid arthritis and to compare the efficacy of these creams in reduction of inflammation. This single blind comparative study was done to determine the efficacy, tolerability and acceptability of topical application of Etoricoxib cream (1% w/w) vs diclofenac cream (1% w/w) and piroxicam cream (0.5% w/w) in Rheumatoid arthritis patients. In this study one hundred and twenty five volunteers suffering with acute Rheumatoid arthritis and age group between 40-60 years were analyzed for assessing the intensity of pain and anti-inflammatory effects of these three creams. The present study revealed that the intensity of pain was lessen up to 98% with Etoricoxib cream, 80% with Diclofenac cream and 84% with piroxicam cream on application of 2 weeks period. Clinically more than 90% improvement was seen in other parameters like tenderness, swelling and functional impairment with Etoricoxib cream as compared to Diclofenac and Piroxicam creams. It had been concluded that at the end of treatment period, Etoricoxib cream was statistically better in reducing pain, tenderness, and swelling and improves the functional ability than Diclofenac cream. Piroxicam cream rated better in these parameter as compared to Diclofenac cream.

Abstract

Candidiasis is a fungal infection caused by yeasts from the genus Candida. It is commonly called oral candidiasis or thrush when it affects the mouth. It is one of the common side effects associated with the long term use of steroid inhalers. Nebulizing therapy with corticosteroids is widely accepted treatment approach for patients with acute exacerbations of Chronic Obstructive Pulmonary Disease. The other side effects of steroid inhalers include hoarseness of voice and dysphonia, which are usually ignorable. We report this case of 74 year old male patient who was on metered dosage inhaler and nebulizer therapy with corticosteroid and presented with oral candidiasis. If oral thrush develops, treatment with oral fluconazole or nystatin mouth wash is beneficial. Proper patient education by the clinical pharmacist to the patient regarding safe and effective usage of inhalers and nebulizers especially corticosteroids can minimize these drug related problems.

 Abstract

Michel addition of indoles with olefins in the presence of FeF3as catalysts afford the corresponding 3-substituted indoles in good to excellent yields and short reaction times are described. The reaction work up is simple and the catalyst can be easily separated from the reaction mixture ,The catalyst is inexpensive, safer, environmentally benign and reused in subsequent reactions.

Abstract

Naftopidil, (R,S)-l-[(2-methoxyphenyl)-l-piperazinyl]-3-(l-naphthyloxy)2-propanol, is a novel antihypertensive agent. Naftopidil is practically insoluble in water. The present study was carried out to enhance dissolution properties of naftopidil through the preparation of solid dispersions using β-cyclodextrine (β-CD) and hydroxy propyl β-cyclodextrine (HP β-CD) as carrier at various proportions by using kneading method and by the physical mixture method. Solid dispersions of Naftopidil with carriers were prepared in different drug: carrier ratios such as (1:1, 1:3, 1:5) using techniques like physical mixing (PM) and kneading method (KM). The drug release profile was studied in pH 1.2 HCl solution. The DSC and FTIR analysis was carried out to study the compatibility between drug and carrier. UV spectrophotometric method was selected for assay as well as in-vitro dissolution studies at 280nm. The solid dispersion using HP β-CD and napthopidil exhibited superior dissolution profile than pure drug.

 Abstract

The present investigation is concerned with development and evaluation of floating tablets containing Norfloxacin. Usingthe hydrophilic polymer hydroxy propyl methyl cellulose (HPMCK100M), gas generating agent sodium bicarbonate and citric acid. A 32 factorial design was applied systematically; the amount ofcitric acid (X1) and amount of HPMCK100M (X2) were selected as independent variables. The dependent variables chosen werepercentage drug release at 8hrs. (Q8), percentage drug release at 12 hours (Q12) and floating lag time that high level of HPMC K100M and citric acid favours preparation of floating sustained release tablet of norfloxacin. The granules were prepared by wet granulation method and evaluated for their granules properties. Tablets were compressedby KarnavatiRimek Mini press1 and evaluated with different parameters like diameter, thickness, average weight, hardness, friability, drug content, in vitro buoyancy study, swelling characteristics, and kinetic release data. The in-vitro release studies indicated that the floating dosage forms containing higher concentration of HPMC K100M showed slower release. The in-vitro release data was treated with mathematical equations, and it was concluded that norfloxacin released from the tablet followed Peppas model with Non-Fickian diffusion. Hence floating drug delivery system of norfloxacin is a promising approach as it can lead to decrease in the frequency of administration and ultimately lead to better patient compliance.

A simple and highly efficient protocol for the synthesis of biologically active 1,8-dioxo- octahydroxanthenes from various aromatic aldehydes with dimedone under catalyst ß- Cyclodextrin in water is reported. This protocol gives wide range of xanthene derivatives with high yield.