Biomedical subjects

Abhishek Gupta

Publications and source records attributed to Abhishek Gupta.

12 recordsLinked to original sources

PubMed2005

A comparison of two methods to determine the solubility of compounds in aerosol propellants.

A new on-line reverse phase HPLC method for determining the solubility of compounds in propellant based metered dose inhaler (MDI) formulations was compared with a conventional method. The new method employs a direct injection from a MDI vial into the needle injector port of a manual injector. To evaluate the two methods, beclomethasone dipropionate (BDP), 5,5-diphenyl hydantoin and 3,3'-diindolylmethane, were used as model compounds in propellant HFA-134a. Comparison was performed by analyzing known and unknown concentrations of BDP in various combinations of HFA-134a and ethanol. In addition, the solubility of 5,5-diphenyl hydantoin and 3,3'-diindolylmethane were determined in HFA-134a using both the new and the conventional methods. The two methods were found to be in good agreement with each other, with the new direct injection technique offering enhanced precision and accuracy along with considerable reduction in analysis time.

Aerosol Propellants↗

PubMed2005

An HPLC method for quantitation of perillyl alcohol in a topical pharmaceutical cream formulation.

A reverse phase high performance liquid chromatographic method for quantitation of perillyl alcohol in a topical cream pharmaceutical formulation was developed. Previously reported methods for analyzing drugs in lipid formulations are relatively complex and time consuming, with extraction, purification and derivatization involved. Through a simple dilution of the cream formulation in isopropyl alcohol, the present assay method enables the direct injection of the samples, on an Alltima C18 5 mu, 150 mm x 2.1 mm, narrow bore column (Alltech Associates, Deerfield, IL). The method includes an isocratic run with acetonitrile-water (40:60, v/v) at 0.35 mL/min for 12 min, followed by a gradient wash with isopropyl alcohol for 20 min, to ensure that all formulation excipients are eluted. Ultraviolet detection was performed at 210 nm with a retention time for perillyl alcohol of 7 min. The high sensitivity assay utilizes a small (5 microL) injection volume for the accurate and precise analysis of perillyl alcohol from a complex cream formulation.

Administration, Topical↗

PubMed2005

Proton MR CSF analysis and a new software as predictors for the differentiation of meningitis in children.

This article describes proton MR spectroscopic analysis of cerebrospinal fluid of 167 children suffering from meningitis and 24 control cases. Quantification of 12 well-separated and commonly observed cerebrospinal fluid metabolites viz., beta-hydroxybutyrate, lactate, alanine, acetate, acetone, acetoacetate, pyruvate, glutamine, citrate, creatine/creatinine, glucose (total) and urea was carried out using Bruker's NMRQUANT software with respect to a known concentration of sodium-3-(trimethylsilyl)-2,2,3,3-d4-propionate (TSP), serving as an external reference. The assignment of urea in CSF is reported for the first time by NMR. The presence of cyclopropane, observed for the first time in tuberculous meningitis overall in 85.1% of cases, acts as a finger-print marker for the differential diagnosis. Multivariate discriminant function analysis was carried out for the proton MR-detected metabolite information and the clinical symptoms data of the meningitis and control cases to find the important descriptors for classification, followed by a re-validation of the entire database. It was found that the control could be differentiated from the disease group with a success rate of 96.4%, followed by the differential diagnosis of tuberculous meningitis with a corresponding value of 77.2%. Excluding the presence of cyclopropane, bacterial meningitis could be classified 84.4% correct and viral meningitis with a rate of 83.3%. It is proposed that the NMR spectroscopic information, along with other routine clinical features, may serve as an additional diagnostic tool for the differential diagnosis of meningitis in children.

Algorithms↗

PubMed2005

In situ characterization of mercury-resistant growth-promoting fluorescent pseudomonads.

Pseudomonas fluorescens strains PRS9 and GRS1 (wild type) were made mercury resistant PRS9Hg(r) (147 microM HgCl2) and GRS1Hg(r) (55 microM HgCl2), respectively, in King's medium by enrichment selection and their in situ root colonization studies were carried out. Mercury resistant mutant of PRS9 was stable and resulted in significant increase in root and shoot fresh weight (P < 0.05). Both the mutants are positive for indoleacetic acid (IAA), 'P' solubilization and siderophore production. PRS9, potent 'P' solubilizer, exhibited higher 'P' solubilization as compared to GRS1. After 2 weeks of inoculation, the population level of wild type PRS9 and its mercury resistant mutants has increased (50 fold). Mercury resistance has no adverse effect on the growth promoting properties of mutants besides being comparable in its morphological and physiological properties with their wild type counterpart. Furthermore, mercury resistant character facilitates rhizospheric competition and thus helpful for establishment of growth promoting strains where metal ions are either limiting and/or present at toxic level.

Biomass↗

PubMed2004

On-line high-performance liquid chromatography method for analyte quantitation from pressurized metered dose inhalers.

A sensitive and rapid, on-line reversed-phase high-performance liquid chromatographic method for quantitation of compounds at low concentrations in pressurized metered dose inhaler (MDI) systems was developed. Traditional methods for the quantitation of compounds in MDI formulations involve the opening of the MDI vial along with sample dilution prior to quantitation. The new method, reported in this study, involves a direct injection from the MDI vial into the needle injector port of a manual injector. Since there is no dilution step involved, this method can be used to quantitate low concentrations of compounds in MDIs with excellent precision. In addition, since the method requires a small injection volume of 5 microl, repeated analyses can be performed in order to generate multiple data points using the same MDI vial. Validation of the method was performed using ethanol-1,1,1,2-tetrafluoroethane (134a)-based MDIs. Beclomethasone dipropionate (BDP), a corticosteroid used for the treatment of asthma, was used as a model compound. Phase separation studies were conducted to investigate the miscibility of the ethanol-134a mixtures with different mobile phase solvent compositions. For the MDI systems in this study, an acetonitrile-water (90:10, v/v) mobile phase at a flow rate of 0.9 ml/min was found to give acceptable chromatography for BDP on a Apollo C18 5 microm, 150 mm x 4.6 mm column (Alltech Associates, Deerfield, IL, USA). Ultraviolet detection was done at 240 nm and the retention time of BDP was 2.7 min. The on-line HPLC method was characterized to be accurate, precise, sensitive, and specific.

Chromatography, High Pressure Liquid↗

PubMed2004

Development of a perillyl alcohol topical cream formulation.

Perillyl alcohol (POH) is a relatively non-toxic agent that has been shown to be a promising anticancer monoterpene in preclinical models. Studies have indicated that topical application of POH may prove to be effective as a skin cancer chemoprevention therapy. The main aim of this study was to determine the influence of several factors on the stability of POH in solution and develop a topical formulation of POH. During preformulation, the influence of pH, temperature, ionic strength, and organic solvents, on the stability of POH was evaluated at four different temperatures: 4, 25, 37, and 48 degrees C. POH was found to degrade under acidic conditions with degradation following apparent first-order kinetics. A hydrophilic topical cream formulation of POH was developed and prepared for toxicology and clinical studies. A reverse phase gradient HPLC method was developed to quantitate POH in the complex formulation. Stability studies of the formulation and a placebo were performed and the formulation was found to be physically and chemically stable over a period of 1 year at 4 and 25 degrees C.

Administration, Topical↗

PubMed2004

Novel method for the determination of solubility in aerosol propellants.

A new on-line reverse-phase high-performance liquid chromatography method to determine the solubility of compounds in propellant-based metered-dose inhaler (MDI) formulations was developed. The new method uses a direct injection from an MDI vial into the port of a manual injector. The MDI vials were coupled with a filtration and injection assembly to filter the excess compound, and deliver the filtrate of the MDI vials to the injector port of the manual injector. A backpressure regulator was connected to the manual injector, to maintain the propellant in the liquid state after injection from the MDI vial. Phase separation studies were conducted to investigate the miscibility of hydrofluoroalkane 134a with different mobile-phase solvent compositions. Characterization of the new direct injection method was done by evaluating sample presentation and chromatography variables to determine the robust nature of the method. Beclomethasone dipropionate in ethanol/hydrofluoroalkane 134a was used as a model system for development. A chemically diverse set of nine compounds was used to evaluate solubility measurement reproducibility. Solubilities were determined at two different temperatures (25 and 37 degrees C) and the average relative standard deviation for all of the solubility measurements was <4%.

Aerosol Propellants↗

PubMed2004

Comparison of the TSI Model 3306 Impactor Inlet with the Andersen Cascade Impactor: solution metered dose inhalers.

The product performance of a series of solution Metered Dose Inhalers (MDIs) were evaluated using the TSI Model 3306 Impactor Inlet and the Andersen Cascade Impactor (ACI). The goal of the study was to test whether the fine particle and coarse particle depositions obtained using the Model 3306 were comparable to those results obtained by ACI testing. The analysis using the Model 3306 was performed as supplied by the manufacturer as well as with 20 cm and 40 cm vertical extensions that were inserted between the Model 3306 and the USP Inlet. Nine different solution formulations were evaluated. The drug concentrations ranged from 0.08 to 0.8% w/w and the ethanol cosolvent concentration varied between 5 and 20% w/w. In general, it was found that good correlations between the two instruments were obtained. However, for formulations containing 10-20% w/w ethanol it is shown that an extension fitted to the Model 3306 yielded an improved correlation to those obtained from the ACI.

Beclomethasone↗

PubMed2004

Bioaccumulation properties of nickel-, cadmium-, and chromium-resistant mutants of Pseudomonas aeruginosa NBRI 4014 at alkaline pH.

Nickel-, cadmium-, and chromium-resistant mutants of Pseudomonas aeruginosa sp. NBRI 4014 are potent growth promontory strains. In the presence of metal(s), they have shown increased cell morphology and could accumulate nickel (2.0874 mM/g), cadmium (2.295 mM/g), and chromium (2.997 mM/g) at pH 9. However, chromium accumulation was maximum, but the toxicity levels of nickel, cadmium, and chromium was ranged from 90 to 504 microM of used metal(s). Bioaccumulation increases up to the fifth day at the highest used metal concentration and then became constant. This suggests their exploitation for detoxification and subsequently loaded biomass treatment for the recovery of accumulated metal(s).

Absorption↗

PubMed2004

Effect of fly ash inhalation on biochemical and histomorphological changes in rat lungs.

Effect of respirable fly ash particles inhalation on lungs of rats was investigated by exposing them to respirable aerosols of size classified power plant fly ash at average concentrations of up to 14.4 +/- 1.77 mg/m3 for 4 hr/day for 28 consecutive days. A remarkable increase was found in blood eosinophil counts of fly ash exposed animals. Biochemical indicators of pulmonary damage viz. lactate dehydrogenase (cytoplasmic enzyme used as a measure of cell injury), gamma-glutamyl transferase (Clara cell damage) and alkaline phosphatase (potential measure of Type 11 cell secretions) in broncho alveolar lavage fluid (BALF) of fly ash exposed group showed significant elevation. Clumping of fly ash particles in the lungs was observed as evidenced by fly ash ladened macrophage accumulation in the alveolar region. The results suggest a damage, local inflammation and remodelling of lung as indicated by hypertrophy and hyperplasia. These changes reflect the toxic effects of the fly ash inhalation.

Air Pollutants↗

PubMed2003

Balancing ethanol cosolvent concentration with product performance in 134a-based pressurized metered dose inhalers.

The effects of formulation parameters on the product performance characteristics of solution metered dose inhalers (MDIs) were determined using ethanol as the cosolvent and HFA 134a as the propellant. Solubility of beclomethasone dipropionate (BDP) was determined in various blends of 134a and ethanol and was shown to increase with ethanol concentration. Product performance was assessed using the APS Model 3306 Impactor Inlet in conjunction with APS Model 3320 Aerodynamic Particle Sizer (APS). Nine solution formulations containing various BDP and ethanol concentrations were studied. Chemical analysis of the Impactor Inlet was performed in order to determine the "respirable" deposition of the MDI system. With increased ethanol concentration, the throat deposition and plate deposition increased and the respirable deposition decreased. The mass median aerodynamic diameter (MMAD) increased with the increasing drug concentration, but did not show a significant increase with an increase in ethanol concentration. This indicates that the efficiency of solution MDIs decreases with increased ethanol concentration. A Maximum Respirable Mass (MRM) was calculated based on the drug solubility at a particular ethanol concentration and the respirable deposition for a 50mcl valve and QVAR actuator for that ethanol concentration. The MRM represents the maximum amount of a given drug that can be delivered to the lungs theoretically and is very sensitive to the solubility profile of the drug. The MRM increased with the increasing ethanol concentration in the formulation until a plateau was reached at an ethanol concentration of 10-15% w/w. The MRM initially increases with increase in ethanol concentration due to the increase in drug solubility. However, at higher ethanol concentrations the increase in drug solubility was negated by a decrease in the respirable deposition. This study illustrates the importance of considering both formulation properties and product performance characteristics when optimizing a metered dose inhaler drug delivery system.

Administration, Inhalation↗

PubMed2002

Development of heavy metal-resistant mutants of phosphate solubilizing Pseudomonas sp. NBRI 4014 and their characterization.

Pseudomonas sp. NBRI 4014 is a potent phosphorus solubilizer (284 microg/ml). It also produced significant levels of siderophore (143.87 microg/ml) and IAA (5.6 microg/ml). Siderotyping indicated it was P. aeruginosa siderovar 1. Cadmium (180 microM), nickel (420 microM), and chromium (370 microM) resistant mutants were developed and characterized for their PGPR properties. Mutants were stable under non-selective pressure. In cases of nickel and cadmium, there were reductions of the siderophore levels. However, they were able to promote root and shoot elongation in soybeans ( Glycine max PK 564) at a significant level (p < 0.05) in the presence of metals unfamiliar to the wild type. The persistence and stability of mutants were evident in rhizospheric soil, thus their exploitation for polluted/contaminated sites was supported.

Indoleacetic Acids↗