Spectroscopic interaction studies of H2 receptor antagonists with levocetirizine.

Patients with allergic rhinitis may also suffer abdominal pain, gastritis or peptic ulcer. In this condition patient may use levocetirizine with famotidine or ranitidine. These drugs have potential to interact with another drug and form complex. The aim of the present study is to evaluate the possible drug drug interaction with each other which may cause increase or decrease of therapeutic effects. For this purpose, validity of Beer Lambert law was checked, lone availability of famotidine (20gm), ranitidine (150gm) and levocetirizine (5mg) were studied in pH simulated to gastric juice (pH 1), pH 4, pH 7.4 and in pH 9 and finally percent availabilities of these drugs were calculated with the help of simultaneous equation. Results showed high percentage of levocetirizine in all pH as 300.32%, 514.41%, 173.38% and 220.68% in presence of famotidine but very low availability of famotidine as 5.36%, 35.38%, 51.87% and 10.89% in presence of levocetirizine. In the case of levocetirizine and ranitidine interaction, zero percent levocetirizine was available at pH 1and 9, 56.28% in pH 4 and 191.1% in pH 7.4. On the other hand, ranitidine was available as 95.36%, 127.93%, 41.47% and 144.3%. These results showed that percentage of all drugs were altered in presence of each other due to drug-drug interaction. This may be due to the charge transfer binding capabilities of the drugs which resulted in significantly changed availability of famotidine, ranitidine as well as levocetirizine.

Synthesis, characterization, antimicrobial and enzyme inhibitory studies of moxifloxacin with aromatic carboxylic acids.

A series of carboxamide derivatives of moxifloxacin has been synthesized. The synthesized derivatives has been characterization by using spectroscopic techniques such as UV-Vis, IR, H1NMR and Mass spectra, which suggested that incoming group has occupied azabicylo groups of selected moxifloxacin at 7th position. Antimicrobial screening has been systematically carried out against various gram-positive, Gram-negatives and fungi in comparison with parent drug. Enzymatic assay were also performed. The results obtained were statistically analyzed by one way ANOVA. The antimicrobial results reveals that the synthesized derivative of moxifloxacin possess good activities against B. subtilis, F. solani, T. rubrum and P. aeruginosa concluding that derivatives are more potent antimicrobial agents as compared to parent drug. While compound B1 solely possess mild enzymatic activity against urease whereas, no other compounds is active against both urease and carbonic anhydrase.

Moxifloxacin-Ester derivatives: Synthesis, characterization and pharmacological evaluation.

It is known that resistance of bacteria is one of the major issues in drug treatment. To cope this issue, it is required to synthesize new analogues which contest against mutated bacteria. This research study included synthesis of several derivatives of moxifloxacin by adding different phenol and alkyl halide at third position of carboxylic group with esterification reaction and the structures of synthesized derivatives were characterized by spectroscopic techniques i.e. 1H NMR, FT-IR and mass-spectrometry. In continuation, antimicrobial activities of the analogues were also evaluated against number of Gram-positive, Gram-negative bacteria and fungi. The experimental results of novel derivatives exhibit significant antibacterial and antifungal profile in which so many synthesized derivatives influenced a similar and enhanced activity against selected microbes that were S. typhi, P. mirabilis, P. aeruginosa, S. flexneri, B. subtilis as compared to the moxifloxacin. Moreover, few innovative derivatives were also produced better anti-fungal activity against F. solani and T. rubrum. Furthermore, the enzymatic activity of all analogues has been analyzed against urease and carbonic anhydrase and concluded that C2 was selected inhibitor of urease enzyme.

Facile LC-UV methods for simultaneous monitoring of ciprofloxacin and rosuvastatin in API, formulations and human serum.

An efficient, selective and cost-effective liquid chromatographic assay was developed and validated for the simultaneous quantification of ciprofloxacin and rosuvastatin in Active Pharmaceutical Ingredients (API), pharmaceutical formulations and in human serum. The chromatographic system consisted of mobile phase methanol-water, 90:10 v/v at pH 3.0 adjusted with o-phosphoric acid, pumped at 1.0 mL/min through a prepacked Purospher Star C18 (5 µm, 25 × 0.46 cm) column and effluent was monitored at the isosbestic point (255 nm) as well as at the λmax of individual drugs (243 and 271 nm). The method was validated over a linear concentration range of 0.25-15 µg/mL for ciprofloxacin and 0.33-20 µg/mL for rosuvastatin (r(2) ≥ 0.999). The ranges of reliable response (limits of detection and quantitation) for ciprofloxacin were 3-15 and 9-45 ng/mL and 17-29 and 52-88 ng/mL, respectively, for rosuvastatin in all API, pharmaceutical formulations and human serum. Analytical recovery from human serum was >98% and relative standard deviation (RSD) was <2. The accuracies were 97.13-102.55 and 97.41-101.31% and precisions in RSD were 0.04-1.90 and 0.02-1.23% for ciprofloxacin and rosuvastatin, respectively. No matrix interferences, ion suppression/enhancement and carry-over were detected. The total assay run time was less than 5 min. In another study, for optimum performance the detector was programmed for multiwavelength scanning at the absorption maxima of each component. Consequently, the linearity range was improved and limit of detection and quantitation values were down to 1-4 and 4-12 ng/mL for ciprofloxacin and 3-5 and 9-15 ng/mL for rosuvastatin, respectively. The validation parameters fitted ICH guidelines through the isosbestic and individual λmax approach. The small sample volume and simplicity of preparation make this method suitable for use in human serum samples, pharmaceutical formulations, quality control, drug-drug interaction studies, clinical laboratories, drug research centers and forensic medical centers.

Liquid chromatographic method for the simultaneous determination of captopril, piroxicam, and amlodipine in bulk drug, pharmaceutical formulation, and human serum by programming the detector.

A highly sensitive LC method with UV detection has been developed for the simultaneous determination of coadministered drugs captopril, piroxicam, and amlodipine in bulk drug, pharmaceutical formulations, and human serum at the isosbestic point (235 nm) and at individual λmax (220, 255, and 238 nm, respectively) by programming the detector with time to match the individual analyte's chromophore, which enhanced the sensitivity with linear range. The assay involved an isocratic elution of analytes on a Bondapak C18 (10 µm, 25 × 0.46 cm) column at ambient temperature using a mobile phase of methanol/water 80:20 at pH 2.9 and a flow rate of 1.0 mL/min. Linearity was found to be 0.25-25, 0.10-6.0, and 0.20-13.0 µg/mL with correlation coefficient >0.998 and detection limits of 7.39, 3.90, and 9.38 ng/mL, respectively, whereas calibration curves for wavelength-programmed analysis were 0.10-6.0, 0.04-2.56, and 0.10-10.0 µg/mL with correlation coefficient >0.998 and detection limits of 5.79, 2.68, and 3.87 ng/mL, respectively. All the validated parameters were in the acceptable range. The recovery of drugs was 99.32-100.39 and 98.65-101.96% in pharmaceutical formulation and human serum, respectively, at the isosbestic point and at individual λmax . This method is applicable for the analysis of drugs in bulk drug, tablets, serum, and in clinical samples without interference of excipients or endogenous serum components.

RP-LC method for the simultaneous determination of gliquidone, pioglitazone hydrochloride, and atorvastatin in formulations and human serum.

The objective of this research was to develop and validate a rapid, economical, and sensitive HPLC method for quantitative determination of gliquidone, pioglitazone hydrochloride, and atorvastatin in tablets and serum. Due to drug combination of these formulations, there has been a need for a reliable quantitative method to determine these drugs in commercial samples and human serum. The chromatographic separation was carried out at ambient temperature with a mobile phase consisting of methanol-water (90 + 10, v/v), with pH adjusted to 3.50 with phosphoric acid. The pump was operated at a flow rate of 1 mL/min, and all analytes were detected at 235 nm. The method was linear over the concentration range of 5-50 microg/mL for all the drugs. The LOD of gliquidone, pioglitazone hydrochloride, and atorvastatin was 0.30, 1.30, and 0.57 microg/mL and LOQ was 0.98, 4.28, and 1.90 microg/mL, respectively. The proposed method was successfully applied to the determination of these drugs in commercial tablets and human serum. The established method was validated with respect to specificity, linearity, precision, accuracy, and ruggedness.

Development and validation of stability-indicating HPLC method for the simultaneous determination of paracetamol, tizanidine, and diclofenac in pharmaceuticals and human serum.

A method is described for the simultaneous determination of paracetamol, tizanidine, and diclofenac in mixtures. The method was based on HPLC separation of the three drugs followed by UV detection at 254 nm. The separation was carried out on a Hypersil ODS, C18 (250 x 4.6 mm id, 10 microm particle size) column using the mobile phase aqueous 0.2% ammonium carbonate-methanol (60 + 40, v/v) at a flow rate of 1 mL/min. The linear regression analysis data were used for the regression curve in the range of 170-10 000 ng/mL for paracetamol, 120-10 000 ng/mL for tizanidine, and 20-10 000 ng/mL for diclofenac. No chromatographic interference from tablet excipients was found. In order to check the selectivity of the proposed method, degradation studies were carried out using hydrolysis (acid, basic, and neutral), thermolysis, and oxidation. The developed method, after being validated in terms of precision, robustness, recovery, LOD, and LOQ, was successively applied to the analysis of pharmaceutical formulations and human serum.

Structural determination of quercusides A and B, new flavonoid glucosides from Quercus incana, by 1D and 2D NMR spectroscopy.

Quercusides A and B, new flavonoid glucosides have been isolated from the chloroform soluble fractions of Quercus incana. Their structures were assigned from (1)H and (13)C nuclear magnetic resonance spectra, distortionless enhancement by polarization transfer (DEPT) and by correlation spectroscopy, heteronuclear multiple quantum correlation (HMQC) and heteronuclear multiple bond correlation (HMBC) experiments. Lupeol, beta-sitosterol and ursolic acid have also been reported from this species.

Synthesis and biological evaluations of enoxacin carboxamide derivatives.

The present work deals with the synthesis of various enoxacin analogues via nucleophilic substitution of 3-carboxylic acid moiety of the drug by aromatic amines. The free carboxylic group was utilized in the formation of amides and the effect of functional group exchange on different biological activities of the parent was evaluated. The structure of these derivatives was established by various spectroscopic techniques and mass spectrometry. The derivatives were evaluated as antibacterial agents against a series of Gram-positive and Gram-negative bacteria whereby some of them displayed considerably improved antimicrobial profile against Gram-negative test strains. Additionally unlike enoxacin, the derivatives were also found to modulate oxidative burst response of phagocytes exhibiting moderate to significant inhibitory activity.

Synthesis, characterization, antibacterial and anti-inflammatory activities of enoxacin metal complexes.

The present work comprises the synthesis of enoxacin (Heno) complexes with various transition metals. Two types of complexes [M(eno)(2)(H(2)O)(2)]3H(2)O(M = Cu(II), Ni(II) or Mn(II)) and [M(eno)(H(2)O)(2)]Cl . 4H(2)O (M = Fe(III)) were obtained. The complexes were characterized by different physicochemical, spectroscopic, and elemental analysis. Results suggest that enoxacin interacts with the metals as a monoanionic bidentate ligand. These complexes were also tested for their antibacterial activity against eleven (11) different microorganisms, and the results were compared with the parent drug. Moreover all the metal complexes were also tested for their ability to scavenge reactive oxygen species where by Mn(II) and Cu(II) complexes exhibited potential to mediate anti-inflammatory response.

Cleaning validation of ofloxacin on pharmaceutical manufacturing equipment and validation of desired HPLC method.

Inadequate cleaning of a pharmaceutical manufacturing plant or inadequate purging of the individual pieces of equipment used in multi-product manufacturing or equipment not dedicated to individual products may lead to contamination of the next batch of pharmaceutics manufactured using the same equipment. Challenges for cleaning validation are encountered especially when developing sensitive analytical methods capable of detecting traces of active pharmaceutical ingredients that are likely to remain on the surface of the pharmaceutical equipment after cleaning. A method's inability to detect some residuals could mean that either the method is not sensitive enough to the residue in question or the sampling procedure is inadequate. A sensitive and reproducible reversed-phase, high-performance liquid chromatographic method was developed for the determination of ofloxacin in swab samples. The method for determining ofloxacin residues on manufacturing equipment surfaces was validated in regard to precision, linearity, accuracy, specificity, limit of quantification, and percent recovery from the equipment surface, as well as the stability of a potential contaminant in a cleaning validation process. The active compound was selectively quantified in a sample matrix and swab material in amounts as low as 0.55 ng/mL. The swabbing procedure using cotton swabs was validated. A mean recovery from stainless steel plate of close to 85% was obtained. Chromatography was carried out on a pre-packed Merck (Dermstadt, Germany) Lichrospher model 100 Rp-18 (5.0 microm, 250 mm X 4.0 mm) column using a mixture of sodium lauryl sulfate (0.024% aqueous solution), acetonitrile, and glacial acetic acid (500:480:20,v/v) as the mobile phase at a flow rate of 1.5 mL/min with a column temperature of 35 degrees C and 294 nm detection. The assay was linear over the concentration range of 2 ng/mL to 2000 ng/mL (R approximately 0.99998). The method was validated for accuracy and precision. The stability of ofloxacin in the swab samples was also assessed. In regard to the 10-ppm acceptance criteria in the succeeding batch, the calculated limit was 437 microg/cm2 while according to the 0.1% dosing approach the calculated value was 116 microg/cm2. The calculated recovery values from swab samples were below these acceptable limits during three consecutive cleaning trials. This confirms that the desired level of cleanliness is achieved using the current cleaning procedures, which were consequently validated.

Fosinopril H(2)-receptor antagonists interaction studies by derivative spectroscopy.

Fosinopril sodium, a phosphinic acid derivative is an angiotensin converting enzyme (ACE) inhibitor, which had been employed for the treatment of hypertension and congestive heart failure; long tem use of ACE inhibitor often result in stress ulcers due to which H(2) receptor antagonists are also concurrently prescribed. The later compete with histamine for H(2) receptors and block gastric acid secretion and some cardiovascular effects of histamine. Our studies are focused on the in vitro availability of fosinopril in presence of commonly used H(2) receptor antagonists. Derivative spectroscopy has been employed for the quantitation of fosinopril and H(2) receptor antagonists followed by linear regression analysis. These studies were carried out in buffers of pH 7.4 and 9 at 37, 48 and 60( masculine)C. Stability constant and thermodynamic function had also been calculated in order to evaluate the reaction mechanism. Commonly prescribed H(2) receptor antagonists like cimetidine, ranitidine and famotidine were used in these studies. Present study clearly indicated that most of the H(2) receptor antagonists studied decreased the availability of fosinopril which conclude that availability of fosinopril can be affected by the concurrent administration of H(2) receptor antagonists.

In vitro availability of ofloxacin in presence of metals essential to human body.

The significance of interaction between ofloxacin and metals ions was evaluated in this study. The absorption of ofloxacin can be negatively affected by concomitant administration of agents containing metal cations. Current studies examine alterations of ofloxacin availability by metal cations and is limited to conventional metal-containing agents such as antacids and mineral supplements. The in vitro availability of ofloxacin was studied in presence of metal ions as magnesium, calcium, chromium, manganese, ferric, ferrous, cobalt, nickel, copper, zinc and cadmium in their salt form in simulated gastric juice, buffers of pH 7.4 and 9 at 37 degrees C by using a modified B.P 2002 dissolution apparatus. UV/VIS (Shimadzu 1601) spectrophotometer was used to analyze the drug by measuring absorbance at 294 nm in simulated gastric juice and at 288 nm in pH 7.4 and 9. The result showed that availability of ofloxacin slightly changed in presence of all metals in all these dissolution mediums.

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 tissues, 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 availability studies of DTZ in presence of commonly used nonsteroidal anti-inflammatory drugs (NSAID's) like diclofenac sodium, flurbiprofen, 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.

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.

A 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(150x4.6 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 236 nm. 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 mg/ml (R2=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 0.0184 microg/ml and the quantitation limit was about 0.056 microg/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 degrees C and 60 degrees 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.

Review: 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 interactions of captopril with H2-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 degrees 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.