Beta-lactamases are enzymes produced by pathogenic microorganisms which exhibit resistance to beta-lactam group of antibiotics and are of considerable clinical importance. In our study, we examined the pathogenic organisms for the secretion of beta-lactamase using the antibiotic ampicillin. The extracted beta-lactamase from the isolates was characterized biochemically for enzyme activity and to initiate their inhibition activities. The protein extracts separated from the potential actinomycetes species were analyzed by targeting against the beta lactamase enzyme activity. The beta-lactamase enzymes from bacterial isolates were purified from the cell free culture extract and activity was estimated spectrophotometrically. The actinomycetes isolated from the soil source were tested for their efficiency to inhibit the beta-lactamase enzyme activity. The protein fractions were extracted by salt precipitation using ammonium sulfate and further salt removal by dialysis technique. The assays for enzyme inhibition were performed by plate well diffusion along with absorbance readings of the enzyme and substrate using spectrophotometer. The beta-lactamase enzyme activity of Proteus sp. had shown highest enzymatic activity followed by Staphylococcus aureus and Pseudomonas sp. The protein extracts of four actinomycetes isolates that showed beta-lactamase inhibition were identified belonging to the genus Streptomyces based on their colony morphology, microscopic observation, and biochemical tests. The beta-lactamase inhibition activities were analyzed to combat antibiotitc resistances exerted by the pathogenic bacteria in infections.
Apoptosis is a developmental and regulated process which may occur as a result of the cytogenetic changes in the cell. Cissus quandrangularis is a xerophytic plant that belongs to the family Vitaceae, commonly distributed throughout the hotter parts of India and Sri Lanka. An attempt had been made to explore the apoptosis-mediated cytotoxic potential of C. quadrangularis on Allium cepa. Cytogenetic activities of the plant were revealed using DAPI staining and in situ visualization of cell death was carried out with the help of Evans blue staining. The presence of clastogenic (nuclear lesions, chromosome bridges, chromosome breakage and pulverization of chromosomes) and non-clastogenic abberations (ball metaphase, stellate metaphase, chromosome clumping and early movement of chromosomes) observed under fluorescent microscope shows the cytotoxic effect of the plant extract. The quantification of cell death was measured by reading absorbance at 600 nm using the spectrophotometer. The cytotoxic effects on Allium root tips shows the apoptotic potential of the plant extract and the present study enlightens the anticancer potential of the plant.
Poor aqueous solubility and dissolution rates are critical problems that hinders the formulation, development and delivery of most of BCS class II and class IV drugs. Gefitinib is a cytotoxic chemotherapeutic drug used in treatment of cancer. The objective of the present study was to investigate the drug-cyclodextrin compatibility study by FTIR and DSC study. The phase solubility study revealed formation of 1:1 stoichiometry binary inclusion complex. The complex was prepared by kneading method. FT-IR spectra provided the data indicating that the HP-β-CD was more effective than β-CD. Differential scanning calorimetry thermograms indicated stronger amorphization and entrapment of gefitinib with HP-β-CD.
The present study is based on development and evaluation of gastroretentive floating tablets of metoprolol succinate by direct compression method, to increase the oral bioavailability of MS. For this, we used a combination of two different hydrophilic polymers that is polyethylene oxide PEO N-80 (X1) and hydroxy ethylcellulose HEC (X2) as independent variables and studied its effect on drug release (as dependent variable) at 20h for MS. A 32 factorial design was used for optimization purpose. The DSC result shows no interaction between two polymers and the drug (MS). Further, in vitro drug release studies have shown a sustained drug release for more than 20h in upper gastrointestinal region (stomach). In vivo study using rabbits have shown increased AUC0-24 (bioavailability) of prepared optimized F6 formulation as compared to the marketed sustain release tablet of MS. Stability study shows no comparable differences on physical parameters and the drug release after 3 months of accelerated stability testing. Hence, we can conclude that a floating tablet containing combination of hydrophilic polymers can be used for gastric retention for more than 20hr which will increase the oral bioavailability of MS.
The present review high-lights the advancement in nanoparticles formulations for the prophylaxis of malaria. An attempt has been made to describe various novel drug delivery systems based on approaches such as polymeric, metallic, natural, chitosan/antisense (AS) and chitosan/sense (S) oligodeoxynucleotide based nanoparticles etc. for the treatment of malaria. The polymer such as chitosan, hydroxyl propyl methyl cellulose and polyvinyl pyrrolidone; the metal like gold and silver and other carriers such as glyceryl-dilaurate, albumin etc. have been explored for the development of novel nanoparticles formulations. These developed nanoparticles formulation have improved the targeted drug delivey of various clinically used antimalarial therapeutic agents such as hydroxychloroquine, curcumin, artemisinin, artemether and lumefantrine etc.
The purpose of this research work was to formulate and evaluate the sustained release tablets of Nateglinide 500mg, an antidiabetic drug. Nateglinide is an oral hypoglycemic agent. The tablets are prepared by direct compression method. The formulations were optimized by incorporating varying composition of Xanthan gum and guar gum as polymers, lactose as flow aid and magnesium stearate as lubricant. All the excipients are tested for compatibility with drug, which revealed that there was no physical and chemical interaction occurred. The Preformulation parameters such as bulk density, tapped density, compressibility index and Hausner’s ratio were analyzed. The friability, drug content, loss on drying, bulk density and percentage yield was evaluated for tablets. The effect of these variables on drug release also studied. The In-Vitro drug release studied were Performed in the USP dissolution apparatus-II using pH 0.1N HCl as dissolution media at 75 rpm speed and temperature of 37oc ± 5oc. The sampling was done at periodic time intervals of 1,4,8,12,16,20 and 24 hours and was replaced by equal volume of dissolution media after each withdrawal. The cumulative amount of drug release at different intervals is estimated using UV method. Based on the evaluation result the formulations F-7 was selected as best formulation. The tablets were found to follow first order kinetics and Higguchi mechanism of drug release, ‘n’ value is less than 0.5 which confirms that the drug release through the matrix was fickian diffusion.
Starting from different ketones 1a-1f , aldehyde 2a-2g , and acetonitriles 3a-3d we synthesize some bioactive β- Acetamido carbonyl compounds 4a-4h . We also attempted to synthesize these compounds by using phenylacetone and deoxybenzoins in place of ketones to afford the products 4i-4j . 1 H-NMR spectra are presented. On the basis of QSAR studies, some compounds were tested for their anti-thrombotic activity in mice. Compound 4f , 4h and 4j were found to exhibit less percentage protection.
A new series of N-[4-(3-Oxo-3-phenyl-propenyl)-phenyl]-2-(4-phenyl-5-pyridine-4yl-4H-[1,2,4]triazole-3-ylsulfanyl)-acetamide have been synthesized by the claisen-schimodt condensation of N-(4-Acetyl-phenyl)-2-(4-phenyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-ylsulfanyl) and various aldehyde. The novel compounds structure has been established on the basis of their substituted aldehyde derivatives. All the compounds were characterized by FT-IR, Mass, and 1H-NMR spectroscopy. These new compounds were evaluated for their in vitro antibacterial activity and anti-fungal activity.
In the present investigation experiment were performed to evaluate the effect of some essential oils on the growth of four test organism i.e., Arthrodermae benhamial , chrysosporium indicum Malbranchea aurantiaca and Microsporium gypseum. Oil of Ocimum basilicum seems to be toxic against A. benhamiae and M. gypseum caused maximum inhibition of 40 mm. Young - Young Oil showed minimum inhibition Zone (9 mm) against A. benhancial and M. aurantiaca . Among the contituents of essential oil of O. americanum , acetate of Eugenol and Geranyl showed toxic effect against almost all the keratinophilic fungi tested here.
Virtual Screening plays an important role to achieve binding affinity, receptor and library pre-processing, docking, scoring and top scoring hits. Optimization of drug ADME parameters continues to play an important role to ensure that the exposure is sufficient to achieve proof of concept, and ultimately efficacy, safely in clinical trials to address unmet medical need. In order to identify potential inhibitors we employed various computational approaches. In this work, we computationally screened and analyzed 60 analogs and further tested their ADME/T profiles. Library of the molecules was constructed based upon structural modifications of pyrimidines and indole nucleus. Structural modifications were performed for the series of 4-(3-hydroxyphenyl)-6-methyl-2-oxo-N-substituted[(Z)-(2-oxoindolin-3-ylidene)amino]-3,4-dihydro-1H-pyrimidine-5-carboxamide derivatives in an order to get better binding energies as compared with Ispinseb. The molecules with better (lower) binding energies were subjected to predict ADMET properties. Ten molecules from the series IP1-IP60 were found acceptable with binding energies and pharmacokinetic properties. On the basis of the binding energies and ADMET properties we have identified compound IP2 and IP4 to be the best interacting molecules. The molecules with acceptable ADMET properties and better binding energies were prioritized for synthesis and anticancer evaluation.
Tribal people use the flower extract of Caesalpinia pulcherrima to cure liver, stomach and skin disorders in Indian traditional medicine. This study aimed to evaluate the protective roles of purified quercetin extracted from suspension culture of C. pulcherrima against selected bacterial and fungal pathogens. A simple protocol was developed for callus production using leaf explants. 2, 4-D (2.5 mg/l), BAP (2.5 mg/l) + kin (1 mg/ml) was effective for optimal callus induction. Subsequently, cell suspension culture was established. Role of effect of elicitors in cell suspension culture was carried. Sucrose, ABA and salicylic acid (SA) at different concentrations influenced cell biomass and quercetin accumulation. Cells cultured in the medium fortified with 45 g/L sucrose without ABA/SA showed the highest quercetin content (16.5 mg/g). Flavonoids was purified, fractionated by HPLC-DAD followed by NMR revealed the presence of quercetin, isoquercetin, quercetrin, rutin, quercetin 3-O-β-D-xyloside, quercetin 3-Oarabinopyranoside, quercetin 3-O- α-arabinopyranosyl (1→2) β-galactopyranoside, isorhamnetin 3-O-rutinoside and an unknown compound. Subsequently, anthocyanin was evaluated for antimicrobial activity against selected Gram-positive bacteria (S. aureus, Bacillus subtilis, and Enterococcus faecalis), Gram-negative bacteria (E. coli, and Pseudomonas aeruginosa) and fungi such as Aspergillus flavus, Candida albicans and Trichophyton rubrum. Quercetin was found to be active against four bacteria and the fungi- Candida albicans. The highest inhibitory effects were found on S. aureus and Enterococcus faecalis. Gram negative bacteria showed more resistance i.e., with insignificant MIC and MBC values. Among the fungi, Aspergillus flavus and Trichophyton rubrum displayed remarkable MIC and MKC values. These results suggest that quercetin may be used as a natural antimicrobial agent. Future works are designed to trace the molecular mechanism of antimicrobial potentiality of quercetin against these tested pathogens
Thalisadi Churna is a reputed drug mentioned in the ancient books of Ayurveda for the treatment of cough, asthma. Churnas are preparations comprising of fine powders of drugs and may be simple or compound. Simple churnas consists of only one ingredient while a compound one consists of more than one ingredient. In ayurvedic system of treatment, churnas are as excellent as are asavas and arishtas for the abolition of diseases. The principle of using Churnas is due to the fact that therapeutic value of most of the substances is greatly increases when they are reduces to vary fine state of subdivion. They are also easily administrable specially in the cases of children where they cannot swallow pills, tablets or capsules. The present paper deals the therapeutic aspects and efficacy of formulation thalisadi churna and comparative evaluation parameters with marketed product.
Present world scenario globally, upto 2010, around 285 million people suffering from Type 2 diabetes making up about 90% of the cases. According to statistics, by 2030, this number is estimated to almost double. Diabetes mellitus occurs throughout the world, but is more common (especially Type 2) in the more developed countries. The greatest increase in prevalence is, however, expected to occur in Asia and Africa, where most patients will probably be found by 2030. The aim of this review is to summarize several studies done for the discovery of new drug using different animal models for in vivo studies (chemical, surgical, and genetic models ) & in vitro models (glucose uptake, pancreatic islet cell lines and insulin secretion).
15-Lipoxygenase is a highly regulated lipid–peroxidating enzyme whose expression and arachidonic acid metabolites are implicated in several important inflammatory conditions. In this scenario, we had performed modeling of arachidonate 15-lipoxygenase B, an enzyme involved in Leucotriene biosynthesis. We wish to contribute to the structural knowledge of arachidonate 15-lipoxygenase B from Homo sapiens . In this pursuit, 3D model of arachidonate 15-lipoxygenase B has been established by homology modeling, choosing the Revised structure of rabbit reticulocyte 15S-lipoxygenase with PDB code 2P0M and Crystal structure of Delta 413-417:GS LOX with PDB code 3FG1 as templates by the MODELLAR9v7 program. The model was extensively validated using protein structure checking tools: PROCHECK, WHAT IF and ProSA. The developed model was analyzed through domain analysis for the presence of various domains. Secondary structural conformations for the developed model were determined using PDBSUM. This study suggests use of this 3D structure as a target of new drugs that act on multidrug resistant varieties of Homo sapiens. Key words: arachidonate 15-lipoxygenase B, Modeller9V7.
There are recent discoveries in the field of Pharmaceutical Technology which have indicated that after bringing down the materials in size range of 1-100nm show unique electrical, optical, chemical and pharmaceutical properties. Mono dispersed nano crystals of various metallic and semiconducting materials, single walled and multi walled nano tubes of carbon and other metallic and non metallic materials along with organic nano materials are being made using established methods. These Carbon nano tubes (CNTs) are useful for the different chemical analysis and its detection since it increases the detection sensitivity many times and thus displays a great role in the development of newer methodologies. Several application of these CNT’s are due to its magnificent and outstanding properties but a drawback which is faced commercially is that these CNT’s and CNTs based devices should be of consistent good quality and devoid of any impurity. Such requirement needs purification and regular sorting of CNTs. It is seen in last few years, the major contribution of Carbon Nano tubes (CNTs) is in the field of cancer treatment and drug delivery systems. This review article throws light on the methods of synthesis, with purification ,sorting techniques for giving different grades to different types of CNTs showing very good adsorption properties which in turn helps in the detection of various chemicals etc. and also research carried out using CNTs for cancer treatment is also discussed in brief.
Ion exchange resins are cross-linked water insoluble polymer-carrying, ionizable functional groups. IER have received considerable attention from pharmaceutical scientists because of their versatile properties as drug delivery vehicles. Research over the last few years has revealed that IER are equally suitable for drug delivery technologies, including controlled release, transdermal, nasal, topical and taste masking. The major drawback of sustained release of extended release or extended release is dose dumping, resulting in increased risk of toxicity. The use of IER has occupied an important place in the development of controlled- or sustained-release systems because of their better drug-retaining properties and prevention of dose dumping. Synthetic ion exchange resins have been used in pharmacy and medicine for taste masking or controlled release of drug. Drug resin complexation converts drug to amorphous form leading to improved drug dissolution. Several studies have reported the use of IER for drug delivery at the desired site of action. Sulfonated and carboxylic resins with a polystyrene backbone are most widely used in clinical medicine. Chemical deterioration of the resins is the result of several different processes. The FDA has the responsibility to define conditions under which safe food additives may be used in the production and preparation of foods and beverages.
Fast dissolving tablets (FDT) of Granisetron hydrochloride were prepared by direct compression method after incorporating superdisintegrants croscarmellose sodium and crospovidone in different concentrations (2.5, 5, 7.5 and 10 mg). Eight formulations having superdisintegrants at different concentration level were prepared to assess their efficiency and critical concentration level. Different type of evaluation parameters for blends and tablets were used. The prepared tablets were characterized by FTIR studies. No chemical interaction between drug and exciepients was confirmed by FTIR studies. The formulation GCS 4 containing croscarmellose sodium showed superior in vitro , in vitro dispersion time and drug release, as compared to other formulations. GCS 4 tablet showed good dissolution efficiency and rapid dissolution. The 50% and 90% of drug release of tablet GCS 4, was found within 0.45 and 2.59 min.
Now day’s formulation research is breaking barriers of conventional methods. Today, active ingredients can be delivered with a level of convenience, performance and bioavailability never seen in the market place. Fast disintegrating or Mouth dissolving tablet (MDTs) is one such novel approach to increase consumer acceptance by virtue of rapid disintegration, self administration without water or chewing. This novel type of delivery system offers convenience for treatment-resistant population who have difficulty in swallowing unit oral dosage form, namely Tablets and Capsules. These formulations are particularly beneficial to pediatric and geriatric patients. It is estimated that 50 % of the population is affected by dysphagia which results in high incidence of non-compliance and ineffective therapy. The aim of this article is to review the ideal properties, significance, characteristics, limitation, choice of drug candidates, challenges in formulation, approaches for preparation of MDTs, Patented technologies on MDTs, Suitable drug candidates for MDTs, Marketed product of MDTs, and Evaluation tests of MDTs
A simple, precise and accurate method was developed and validated by using a simple solvent system for paclitaxel (PTX) bulk and tablet dosage form. In the developed method, PBS (phosphate buffer pH-7.4) and methanol was used as solvents. The λ max was determined to be 230 nm. The linearity concentration range was 2-20μg/ml with the correlation coefficient of 0.993. The percentage recovery for PTX was found to be 99.82 to 100.48%. Keywods: Paclitaxel; Methanol; Absorption Maxima.
Separation of the leaves extracts of Muehlenbeckia platyclada Meissn based on in vitro antibacterial activity against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 resulted in the isolation of a flavonol glycoside. The aglycone was identified as quercetin based on UV, IR, NMR and mass spectral studies. Keywords: Muehlenbeckia platyclada Meissn, leaves extract, antibacterial activity, flavonol glycoside, quercetin.
