Synthesis, characterization and enzyme inhibitory activity of new pyrazinamide iron complexes

The present paper deals with synthesis, characterization and amylase inhibitory activity of pyrazinamide [PYZ] with iron in its both [II] and [III] oxidation states. The synthesized complexes were characterized on the basis of IR, UV, [1]H-NMR, [13]C-NMR, elemental analysis and SEM. Changes in IR data shows that PYZ form complex with octahedral geometry and binding sites are ring nitrogen and carbonyl group, wherein two sides are satisfied with two chloride ions. SEM images indicate the crystalline state and surface morphology of PYZ and its complexes. Elemental analysis proves the composition of complexes. Pyrazinamide and the complexes showed no significant effect on amylase activity but the activity was inhibited in the presence of ferrous chloride

Cephradine antacids interaction studies

The present work comprises of interaction studies of cephradine with antacids. Cephradine is included among the first generation cephalosporin, which is active against a wide range of Gram positive and Gram-negative bacteria including penicillinase-producing staphylococci. Since the presence of complexing ligand may affect the bioavailability of a drug in blood or tissue, therefore, in order to study the probable interaction of cephradine with antacids all the reaction conditions were simulated to natural environments. Antacids are commonly used in patients complaining of GI irritations. The behavior of cephradine in presence of seven antacids i.e., simethicone, magaldrate, magnesium carbonate, magnesium hydroxide, magnesium trisilicate, sodium bicarbonate and aluminium hydroxide was studied by using standard dissolution apparatus. Cephradine was monitored both by UV and by high performance liquid chromatography. The results revealed that antacids containing polyvalent cations retarded the in vitro availability of cephradine. Moreover, these studies indicated that cephradine was strongly adsorbed on antacids; magnesium trisilicate and simeco tablets [powdered] exhibited relatively higher adsorption capacities

In vitro interaction studies of diltiazem with NSAID's using UV spectrophotometry and RP-HPLC techniques

Diltiazem [DTZ] is a well-known cardiovascular drug used clinically in the treatment of angina pectoris and hypertension. Present paper deals with the in vitro available studies of DTZ in presence of commonly used nonsteroidal anti-inflammatory drugs [NSAID's] like diclofenac sodium, flubiprofen, mefenamic acid and meloxicam. Simultaneous administration of both types of drugs may alter the antihypertensive effect of DTZ. These studies were carried out using BP 2005 dissolution test apparatus in simulated human body environments at body temperature and at elevated temperature in order to study the kinetics and energitics of these interactions. Both the drug in each case were analyzed either by measuring the absorbance of aliquots on a UV/VIS spectrophotometer, or by RP-HPLC method. Present study clearly indicated that most of the NSAID's studied bind to DTZ forming charge transfer complexes, evident from the high availability of DTZ. Hence, concurrent administration of NSAID's with DTZ is not recommended

In vitro availability studies of enoxacin in presence of H[2] receptor antagonists

Enoxacin is a second-generation quinolone with increased antibacterial activity both in potency as well as in terms of broad spectrum against a wide range of clinically important pathogens over the first generation quinolones and produces its effect by inhibiting bacterial enzyme DNA gyrase. There are a number of drug interactions reported for enoxacin. On the other hand H[2]-receptor antagonists block gastric acid secretion and some cardiovascular effects of histamine. As the later drug are used for a long-term therapy, they may be coadministered with other drugs. In present study in vitro release of enoxacin in presence of cimetidine, ranitidine and famotidine has been studied on a B.P. 2003 dissolution test and compared with the availability of enoxacin and H[2]-receptor antagonists alone. The interacting drugs were analyzed spectrophotometrically. These studies were carried out in simulated gastric juice, simulating empty stomach, simulated intestinal juice [pH 9] and buffers of pH 7.4 simulating blood pH at 37 degree C. In order to support these interaction studies, the effect of H[2]-receptor antagonists on the antibacterial efficacy [MIC] of enoxacin was also studies by turbidity method and compared with parent drug against Staphylococcus aureus, Staphylococcus pyogens, Staphylococcus pneumonia, Enterococcus, Escherichia coli, Salmonella typhi, Pseudomonas aeruginosa, Klebsiella pneumonia, Proteus mirabilis and Bacillus subtilis. On the basis of these results, it is suggested that enoxacin should be coadministered with care along with H[2]-receptor antagonists especially in case of ranitidine; although chances of adverse reactions are rare but decrease in MIC of enoxacin may result in delayed effect or require prolonged use of the drug

Fabrication of solid nanoparticles for drug delivery

The use of nanoparticles in biotechnology presents a growing interest for the numerous possibilities offered by combining the world of materials, with its advanced technologies and their diverse properties, and the biological world, with its elaborate molecular architectures, properties and functions. Different nanoparticles are attractive for their intrinsic properties of optical transparency, controllable porosity, chemical inertness and biocompatibility. Various synthetic methods have been developed for preparing nanoparticles with well-controlled sizes and shapes. Research in nanotechnology and biopharmaceutics or collectively nanomedicine has recently taken a new dimension, with amazing variety of methods for fabrication of nanoparticles. It is now possible to enhance or control drug delivery, this is required in case of poorly soluble drug, or drugs to cross blood brain barrier [BBB]. Moreover, this technique can also be utilized for targeted delivery of drugs. There are number of methods reported in literature for the fabrication of nanoparticles. These include Sol-Gel technique, spraying the drug solution in vacuum, solvent diffusion or precipitation method. The former two techniques are mostly used to fabricate porous nanoparticles. Present paper reviews these techniques so as to give an idea to those planning to start with the fabrication of nanoparticles in a particular area of interest

Optimization of levofloxacin analysis by RP-HPLC using multivariate calibration technique

A rapid and sensitive reverse phase high performance liquid chromatographic [RP-HPLC] method for the analysis of levofloxacin from bulk materials, dosage formulations and human serum is described. This isocratic method employs, a Nucleosil, C18 [10um, 25 cm x 0.46 cm] column with a mobile phase of water and acetonitrile [6:5], where in phosphoric acid was used to adjust the pH to 2.9 and propylparaben as an internal standard. Optimization of levofloxacin analysis was carried out using multivariate calibration technique and detector response was recorded at five different wave lengths. A linear response [r > 0.9999] was observed in the range of 40 to 10000 ng ml-1. The method shows good recoveries, intra and inter-day relative standard deviations were less than 1.2%. Validation parameters as specificity, accuracy and robustness were also determined. The method can conveniently be used for analysis of levofloxacin pharmacokinetic levels in human serum and pharmaceutical formulations

In vitro interactions of captopril with H[2] receptor antagonists

Captopril is effective in the treatment of hypertension of all grades of severity. H2-receptors antagonists block gastric acid secretion and some cardiovascular effects of histamine. In view of the fact that, simultaneous administration of both drugs may alter the antihypertensive effect of captopril, present paper deals with the in vitro availability studies of captopril in presence of commonly used H2-receptor antagonists like cimetidine, ranitidine and famotidine. In order to simulate various pH levels in GI tract and to find out the kinetics and energetics of captopril-H2 -receptor antagonist interactions, these studies were carried out in buffers of pH 4, 7.4 and 9 at 37°C and at elevated temperatures. These studies clearly indicate that most of the H2-receptor antagonists bind to captopril, forming charge-transfer complexes. As a result, the availability of captopril was affected by the concurrent administration of H2- receptor antagonists. Accordingly coadministration of both the drugs should be avoided

Spectrophotometric methods for the simultaneous analysis of meclizine hydrochloride and pyridoxine hydrochloride in bulk drug and pharmaceutical formulations

Three new spectrophotometric procedures for the simultaneous determination of pyridoxine hydrochloride and meclezine hydrochloride are described. The first method depends on the application of simultaneous equation to resolve the interference due to spectral overlapping. The analytical signals were measured at 231 and 220 nm. Calibration graphs were established for 1 to 20 micro GmL-1 for pyridoxine hydrochloride and 0.5 to 10 micro GmL-1 for meclezine hydrochloride in binary mixture. In the second method, the determination of pyridoxine hydrochloride and meclezine hydrochloride was performed by measuring the absorbances at 290 and 235 nm in the simple absorbance spectra of their mixture. In third method a yellowish orange complex of pyridoxine hydrochloride was formed with ferric chloride, which absorbs in the visible region with

Multivariate calibrations in UV spectrophotometric analysis

Calibration allows the user to relate instrumental measurements to the sample of interest. Multivariate calibration allows for the analysis of several measurements from several samples or specimens. The method contributes to the two steps procedure where step one involves the calibration of data and second step involves the prediction that are made or based on the calibration. In calibration, indirect measurements are made from samples where the amount of the analyte has been predetermined, usually by an independent assay or technique. These measurements, along with the predetermined analyte levels, comprise a group known as the calibration set. This set is used to develop a model that relates the amount of sample to the measurements by the instrument. In some cases, the construction of the model is simple due to a certain relationship, such as Beer's Law in the application of UV spectroscopy. Unlike spectroscopy, other cases can be much more complex, and it is in these cases where construction of the model is time-consuming step. Once the model is constructed, it can predict analyte levels based on measurements of new samples. It can be used to separate samples from interferences without the need of highly selective measurements for the analyte. Calibration techniques [used in the calibration step] differ in determining coefficient values for the preceding or similar equations

In vitro hypoglycemic activity of methanolic extract of some indigenous plants

Pakistan is rich in medicinally important plants and has ancient herbal treatment methods. Present work is based on the study of six indigenous plants Eugenia jambolana, Lawsonia inermis, Momordica charantia, Morus alba, Nigella sativa and Trigonella foenum graecum which show the inhibitory effect of glucose utilization, and are in use as hypoglycemic agents of varying degree in traditional system of medicine. The glucose uptake activity of [methanolic extracts] of these plants was tested in vitro and glucose was estimated by glucose oxidase method. The results in three different media revealed that, hypoglycemic activity is more prominent in neutral and basic media as compared to acidic medium

validated method for the analysis of diltiazem in raw materials and pharmaceutical formulations by RP-HPLC

A simple, selective and rapid reversed phase high performance liquid chromatographic [HPLC] method for the analysis of diltiazem [DTZ] in bulk material and pharmaceutical formulations has been developed and validated. Sample was resolved on a Hypersil, ODS, C- 18 [1 50x4.6 mm, 5 micron] column. The mobile phase consisted of methanol- water [80:20 v/v, pH 3.1 adjusted with phosphoric acid] was delivered at a flow rate of 0.5 ml/min at ambient temperature and the retention time was about 2.6 minutes with symmetrical peaks. Studies were performed on an HPLC system equipped with a UV/ visible detector at 236nm. Flurbiprofen [FLR] was used as an internal standard. The developed method gave good resolution between diltiazem and internal standard. The method is specific to DTZ and able to resolve the drug peak from formulation excepients. The calibration curve was linear over the concentration range of 0.195-50 micro g/ml [R[2] = 0.999]. The proposed method is accurate [the accuracy results were 94.1-99.39 for diltiazem recoveries], precise [The intraday and interday precision CVs were 0.035-2.2%] and linear within the desired range. The lower limits of detection for DTZ was found to be 0.0 184 microg/ml and the quantitation limit was about 0.0564 micro g/ml and therefore could be employed as a more convenient and efficient option for the analysis of diltiazem and its related compounds in drug substance and formulations

In vitro activity of cefadroxil, cephalexin, cefatrizine and cefpirome in presence of essential and trace elements

Evidences supporting the introduction of metallic elements in several biological processes are rapidly accumulating. Likewise, many drugs possess modified toxicological and pharmacological properties when in the form of metal complexes. In order to ascertain the role of various essential and trace element complexation on the antibacterial activity of various cephalosporins, the synergistic or antagonistic behavior of cefadroxil, cephalexin, cefatrizine and cefpirome in presence of essential and trace elements has been studied and compared with the parent drug. The essential and trace elements comprised of magnesium, calcium, chromium, manganese, ferric, cobalt, nickel, copper, zinc and cadmium in the form of their chloride. These studies were carried out by observing the minimum inhibitory concentration [MIC] using agar dilution method and compared with the MIC'S of the standard cephalosporins against various species of Gram [+] and Gram [-] microorganisms such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis, Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella typhi and Shigella dysenteriae. Different dilutions of cephalosporins and salts of essential and trace elements were used in these studies. The ratio of the drug and metal salts was 1:1 and the reactions were carried out at two different temperatures as 37°C and 60°C in order to study the complex formation. The aim of our study was on one hand to evaluate the changes in microbiological activity of the standard cephalosporins after in vitro metal interactions to study the synergetic or antagonistic behavior of the later through the difference in MICs values of these cephalosporins and on the other hand to access the bioassay directed extent of drug metal complexations. Our investigation reveal that interaction of above cephalosporins with essential and trace elements cause antagonistic effect in many cases which was shown by decrease in antimicrobial activity of cephalosporins and MIC values were increased

Nanoparticles in delivery of cardiovascular drugs

Everything in nature is built upward from the atomic level to define limits and structures to everything. Nanomedicines marked the field of medicine from nanobiotechnology, biological micro-electromechanical systems, microfluidics, biosensors, drug delivery, microarrays to tissue microengineering. Since then nanoparticles has overcome many challenges from blood brain barrier to targeting tumors. Where solid biodegradable nanoparticles were a step up liposome, targeting nanoparticles opened a whole new field for drug delivery. In this article, we attempt to discuss how the pioneered technique is serving in the drug delivery to cardiovascular system and how with the manipulation of their properties, nanoparticles can be made to fulfill desired function. Also how nanocarriers are improving molecular imaging to help improve diagnosis and treatment of cardiovascular disease is focused in this article

In vitro availability of metformin in presence of H[2] receptor antagonists

Metformin is a guanidine derivative used for the treatment of NIDDM. As it is used for a long-term therapy, it may be coadministered with other drugs. Present paper deals with the in vitro availability studies of metformin in presence of commonly used H2 receptor antagonists. The later drugs compete with histamine for H2 receptors and block gastric acid secretion and some cardiovascular effects of histamine. These studies were carried out in simulated gastric juices, simulating empty and full stomach, simulated intestinal juice and buffers of pH 7.4 simulating blood pH at 37°C on a B.P. 2003 dissolution test apparatus. Commonly prescribed H2 receptor antagonists like cimetidine, ranitidine and famotidine were used in these studies. The present study clearly indicated that availability of metformin can be altered in presence of most of the H2 receptor antagonists studied except in presence of famotidine at pH 4 where the drug concentration remains unaltered. The availability of metformin was increased in simulated gastric juice, pH 7.4 and pH 9 [except ranitidine at pH 9] whereas the decrease in availability was observed in presence of cimetidine and ranitidine at pH 4 and ranitidine at pH 9. On the basis of these results, it is can be suggested that metformin should be coadministered with care along with H2 receptor antagonists especially in case of ranitidine; although chances of adverse reactions are rare but decrease availability of metformin may result in delayed effect. On the other hand, increase in metformin concentration may result in hypoglycemic effects

PR-HPLC method for the assay of cefpirome and its application in drug-metal interaction studies

An accurate, sensitive and least time consuming RP-HPLC method for the estimation of cefpirome in the presence of essential and trace metal has been developed and validated. Cefpirome was eluted from a B144A, OD-5-100, C18 [150 x 4.6 mm] column at room temperature with a mobile phase consisting of MeOH:H2O [15:85,% v/v] at a flow rate of 1 ml/minute, while UV detection was performed at 265 nm. The detection limit of cefpirome was 10 ng. Drug metal interaction studies were carried out at 37 oC to monitor the complexation of drug with metal ions. These studies were beneficial to determine the drug in therapeutic concentrations inside human body as well as its complexation with metal cations. The metals essential to human body like Mg[II], Ca[II], Cr[II], Mn[II], Fe [III], Co[II], Ni[II], Cu[II], Zn[II] and Cd[II] were in the form of chlorides. The carboxylic group of the dehydrothiazine ring has more binding capacity relative to other group that augments the drug complexes with essential and trace elements. The established HPLC method is rapid, accurate, and selective, because of its sensitivity and reproducibility. The order of complexation was ferric > chromium > copper > nickel > cadmium > zinc > magnesium > manganese > calcium > cobalt

Fabrication of nanoparticles within polymeric pores for controlled release of drug

Nanotechnology, a multidisciplinary scientific undertaking, involves creation and utilization of materials, devices or systems on the nanometer scale. The field has enabled the development of an amazing variety of methods for fabricating nanoparticles in recent years. The technology is expected to create innovations and play a critical role in the field of biopharmaceuticals especially in controlled release of drug delivery. Sol-gel technique is one of the most widely used techniques to fabricate porous nanoparticles within the polymer. Such nanoparticles have also applications in vascular drug delivery and release, site-specific targeting [passive as well as active targeting], as well as transfusion medicine. This article concentrates mainly on fabrication of porous nanoparticles, its characterisation and its use for controlled release of drug. It also encompasses the strategies that have been used to translate and fabricate a wide range of particulate carriers e.g., nanospheres, liposomes, micelles, oil-in-water emulsions, with prolonged circulation and/or target specificity. With regard to the targeting issues, attention is particularly focused on the importance of physiological barriers. we have also critically reviewed and assessed the fate and activity of biodegradable/bioerodable polymeric drug delivery vehicles because the uniformity in degradation of these polymers is questionable

In vitro availability of atorvastatin in presence of losartan

Hydroxymethylglutaryl-coenzyme A reductase inhibitors [statins] are a group of cholesterol lowering agents that have become the largest selling drugs in the world. They are of proven clinical benefit in coronary heart disease, at least in those patients who do not have overt chronic heart failure [CHF]. Co-administration of statins with angiotensin II receptor blockers [ARBs] is most common, since there is strong synergy between hypertension and hypercholesterolemia in terms of risk factors for the development of cardiovascular diseases. In present paper, we describe the in vitro availability of atorvastatin, a potent HMG-CoA reductase inhibitor, in presence of losartan potassium, which is a non-peptide angiotensin II receptor antagonist. These studies were carried out at 37, 48 and 60

Porous nanoparticles in drug delivery systems

This article concentrates mainly on fabrication of porous nanoparticles, its characterisation and its use for controlled release of drug. It also encompasses the strategies that have been used to translate and fabricate a wide range of particulate carriers e.g., nanospheres, liposomes, micelles, oil-in-water emulsions, with prolonged circulation and/or target specificity. Sol-gel technique is one of the most widely used techniques to fabricate porous nanoparticles within the polymer. Such nanoparticles have also applications in vascular drug delivery and release, site-specific targeting, as well as transfusion medicine. With regard to the targeting issues, attention is particularly focused on the importance of physiological barriers. We have also critically reviewed and assessed the fate and activity of biodegradable polymeric drug delivery vehicles because the uniformity in degradation of these polymers is questionable. This article will highlight rational approaches in design and surface engineering of nanoscale vehicles and entities for site-specific drug delivery. Potential pitfalls or side effects associated with nanoparticles are also discussed

Degradation studies of azithromycin and spectorphotometric determination in pharmaceutical dosage forms

A simple, accurate and rapid spectrophotometric method for the estimation of azithromycin has been developed by the acidic hydrolysis of the drug with sulfuric acid and monitoring the absorbance at 482nm. All variables affecting the reaction conditions such as sulfuric acid concentration, heating time, temperature and dilution solvents were carefully studied. Analytical parameters such as stability, selectivity, accuracy and precision have been established for the method and evaluated statistically to assess the application of the method. The method was applied successfully for the assay of azithromycin dihydrate in pure and pharmaceutical dosage forms as tablets, capsules and suspensions. The method was found to have the advantages for simplicity, stability, sensitivity, reproducibility and accuracy for using as an alternate to the existing non-spectrophotometric methods for the routine analysis of the drug in pharmaceutical formulations and also in pharmaceutical investigations involving azithromycin dihydrate

Synthesis and characterization of glibenclamide complexes of magnesium, chromium, cobalt, nickel, zinc and cadmium salts

Glibenclamide is the commonly used hypoglycemic agent in NIDDM. Metal complexes of glibenclamide have been synthesized by reaction with different metals such as magnesium, chromium, cobalt, nickel, zinc and cadmium in the form of their chlorides. These complexes were characterized by their physical characteristics, 1H-NMR, IR and Atomic absorption studies