Determination of aminophylline based on fluorescence quenching of amino-functionalized graphene quantum dots induced by photoilluminated riboflavin-aminophylline system.

A new method based on fluorescence spectroscopy for the sensitive determination of aminophylline (AP), an antiasthmatic drug, was developed in this work. Amino-functionalized graphene quantum dots (afGQDs) were synthesized based on a two-step method and they were characterized by transmission electron microscope, UV-vis absorption spectrum and infrared spectrum. The fluorescence of afGQDs was quenched by riboflavin (Rf) via both dynamic quenching and inner filter effect. Photoilluminated Rf-AP system in the presence of oxygen produced hydroxyl radicals (OH). The latter accepted electrons from afGQDs owing to a photo-induced electron transfer process and led to the further fluorescence decline. The changing extent of the fluorescence intensity was found to be proportional to the concentration of AP in the range of 0.10-10 µg mL-1 and the limit of detection arrived at 40 ng mL-1. The proposed method was successfully employed for the determination of AP in a pharmaceutical sample and the recovery rate varied in the range of 99%-106%.

Biological and physicochemical stability of ceftazidime and aminophylline on glucose parenteral solution

Ceftazidime is a broad spectrum antibiotic administered mainly by the parenteral route, and it is especially effective against Pseudomonas aeruginosa. The period of time in which serum levels exceed the Minimum Inhibitory Concentration (MIC) is an important pharmacodynamic parameter for its efficacy. One of the forms to extend this period is to administer the antibiotic by continuous infusion, after prior dilution in a Parenteral Solution (PS). The present work assessed the stability of ceftazidime in 5% glucose PS for 24 hours, combined or not with aminophylline, through High Performance Liquid Chromatography (HPLC). The physicochemical evaluation was accompanied by in vitro antimicrobial activity compared MIC test in the 24-hour period. Escherichia coli and Pseudomonas aeruginosa were the microorganisms chosen for the MIC comparison. The HPLC analysis confirmed ceftazidime and aminophylline individual stability on PS, while the MIC values were slightly higher than the mean described in the literature. When both drugs were associated in the same PS, the ceftazidime concentration by HPLC decreased 25% after 24 hours. Not only did the MIC values show high loss of antibiotic activity within the same period, but also altered MIC values immediately after the preparation, which was not detected by HPLC. Our results indicate that this drug combination is not compatible, even if used right away, and that PS might not be the best vehicle for ceftazidime, emphasizing the importance of the MIC evaluation for drug interactions.

Ceftazidima é um antimicrobiano administrado por via parenteral, que apresenta amplo espectro de ação, principalmente contra Pseudomonas aeruginosa. O tempo em que a concentração sérica de ceftazidima permanece acima da concentração mínima inibitória (MIC) é um importante parâmetro farmacodinâmico para a determinação da eficácia antimicrobiana e pode ser potencializado através da utilização de infusão contínua em soluções parenterais (PS). Este artigo visa a avaliar a estabilidade da ceftazidima em solução de glicose 5%, na presença e na ausência do fármaco aminofilina, através de cromatografia líquida de alta eficiência HPLC e MIC durante o período de 24 horas. Os microorganismos selecionados para a determinação do MIC foram Escherichia coli e Pseudomonas aeruginosa. Os ensaios em cromatógrafo líquido confirmaram a estabilidade dos fármacos ceftazidima e aminofilina quando são individualmente associados em PS, enquanto os valores de MIC ficaram maiores que os valores encontrados na literatura. Quando ambos os fármacos foram associados na mesma solução parenteral a concentração de ceftazidima obtida por HPLC diminuiu 25% depois de 24 horas. Os valores de MIC mostraram maior decaimento da atividade antimicrobiana neste mesmo período e também valores de MIC alterados nas soluções preparadas no tempo zero, decaimento este que não foi detectado em HPLC. Os resultados indicaram incompatibilidade na associação dos fármacos em PS, enfatizando a importância dos resultados de MIC para interações de fármacos.

Stability of furosemide and aminophylline in parenteral solutions / Estabilidade de furosemida e aminofilina em soluções parenterais

Parenteral solutions (PS) are one of the most commonly used drug delivery vehicles. Interactions among the drug, components in the drug's formulation, and the PS can result in the formation of inactive complexes that limit efficacy or increase side effects. The aim of this work was to evaluate possible interactions between the drugs and PS, assess drug stability and to identify degradation products after 20 h at room temperature. Furosemide (FSM) and Aminophylline (APN) were added to PS containing either 20 percent mannitol or 0.9 percent NaCl at pH 6.5-7.5 and 10-11. Their behavior was studied individually and as an admixture, after 1 h oxidation with H2O2, using a spectrophotometer and HPLC. Individually, FSM and APN added to 20 percent mannitol and 0.9 percent NaCl solutions had the highest stability at pH 10-11. When FSM and APN were combined, the behavior of FSM was similar to the behavior observed for the drug individually in the same solutions. With the drugs combined in 20 percent mannitol pH 10-11, HPLC showed that both drugs were stable after a 20 h period yielding two distinct peaks; in oxidized samples, the elution profile showed four peaks with retention times unrelated to the untreated samples.

Soluções parenterais de grande volume são frequentemente utilizadas no ambiente hospitalar para a veiculação de fármacos. No entanto, possíveis incompatibilidades entre as estruturas dos fármacos, em diferentes veículos de administração, podem gerar possíveis associações antagônicas ou sinérgicas, resultando em alterações das propriedades físico-químicas, consequentemente, dos efeitos farmacológicos e das respostas clínicas esperadas. Este artigo avaliou a estabilidade e a possível formação de produtos de degradação entre os fármacos furosemida e aminofilina quando estes foram veiculados em soluções parenterais, após o preparo e após o período de 20 h. Furosemida e aminofilina foram adicionadas às soluções de 20 por cento manitol e 0,9 por cento NaCl nos valores de pH 6,5-7,5 e 10-11. A estabilidade dos fármacos foi avaliada individualmente, combinada e após degradação com peróxido de hidrogênio através de espectrofotometria de UV e HPLC. Furosemida e aminofilina individualmente avaliadas mostraram alta estabilidade em ambas as soluções estudadas nos valores de pH 10-11. Quando os fármacos foram combinados o comportamento da furosemida foi similar ao observado na ausência de aminofilina. Os fármacos combinados em 20 por cento manitol pH10-11 por HPLC foram estáveis após o período de 20 h. Após degradação o perfil de cromatograma encontrado foi diferente do observado na ausência de degradação mostrando que o método é indicativo de estabilidade.

A novel spectrophotometric method for the determination of aminophylline with boric acid in pharmaceutical and mixed serum samples.

This paper firstly describes a novel method to determine aminophylline (Ami) with boric acid (BA) by spectrophotometry. The study indicates that at pH 12.00 the absorbance of Ami decreases when BA is added. A simple, rapid, sensitive and reliable novel method based on the product of Ami and BA is obtained. Beer's law is obeyed in the range of Ami concentrations of 0.20-200 microg ml(-1). The equation of linear regression is A=-2.57309x10(-4)-0.00355C (microg ml(-1)), with a linear correlation coefficient of 0.9969 and RSD 0.28%. The method is successfully applied to the determination of Ami in pharmaceutical samples and mixed serum samples, and average recoveries were in the range of 97.1-105.9%.

A novel spectrophotometric method for the determination of aminophylline in pharmaceutical samples in the presence of methanol.

A rapid, simple and sensitive method for the determination of aminophylline (Ami) using sodium 1, 2-naphthoquine-4-sulfonate (NQS) and methanol is established in this paper. It is based on the fact that a russety product can be formed by the reaction between aminophylline (Ami) and sodium 1, 2-naphthoquine-4-sulfonate (NQS) in pH 13.00 buffer solution. When methanol is added to the solution, the sensitivity of the color development reaction between Ami and NQS is improved, and the color of the system of NQS-Ami becomes a salmon pink. Beer's law is obeyed in a range of 4.97-69.5 microg ml(-1) of Ami at the maximum absorption of 453 nm (epsilon=4.87 x 10(3) l mol(-1) cm(-1)). The linear regression equation of the calibration curve is A=0.14458+0.00832C (microg ml(-1)), with a linear regression correlation coefficient of 0.9944. The detection limit is 0.7 microg ml(-1) (3sigma/k), R.S.D. is 1.1% and the recovery rate is in range of 92.5-105%. Furthermore, this method has been successfully applied to the determination of Ami in pharmaceutical samples.

Influence of aminophylline on the anticonvulsive action of gabapentin in the mouse maximal electroshock seizure threshold model.

Accumulating evidence indicates that aminophylline [theophylline(2) x ethylenediamine] markedly attenuates the anticonvulsant action of conventional antiepileptic drugs in experimental animal models of epilepsy and evokes severe seizure activity in patients treated with this methylxanthine. The objective of this study was to determine the influence of acute (single) and chronic (twice daily for 14 consecutive days) treatments with aminophylline on the anticonvulsant potential of gabapentin (a second-generation antiepileptic drug) in the mouse maximal electroshock seizure threshold model. Additionally, the effects of acute and chronic administration of aminophylline on the adverse effect potential of gabapentin in terms of motor coordination impairment were assessed in the chimney test. To evaluate pharmacokinetic characteristics of interaction between drugs, total brain concentrations of gabapentin and theophylline were estimated with high-pressure liquid chromatography and fluorescence polarization immunoassay, respectively. Results indicated that gabapentin (at doses of 75 and 100 mg/kg, i.p.) increased the threshold for electroconvulsions in mice. Aminophylline in non-convulsive doses of 50 and 100 mg/kg (i.p.), both in acute and chronic experiments, did not attenuate the anticonvulsant potential of gabapentin in the maximal electroshock seizure threshold test in mice. Similarly, aminophylline at a dose of 100 mg/kg had no impact on the adverse effect potential of gabapentin in the chimney test. Pharmacokinetic evaluation of total brain concentrations of gabapentin and theophylline revealed no significant changes in total brain concentrations of the drugs after both, acute and chronic applications of aminophylline in combination with gabapentin. The data show that aminophylline did not alter the ability of gabapentin to protect mice against seizures induced by electroconvulsive shock. The observed interaction between gabapentin and aminophylline in both acute and chronic experiments was pharmacodynamic in nature.

Quantitative determination of diclofenac sodium and aminophylline in injection solutions by FT-Raman spectroscopy.

The FT-Raman quantification of diclofenac sodium and aminophylline commercial injection solutions was performed. The efficiency of various spectra treatment procedures including classical univariate intensity ratio and multivariate partial least squares (PLS) and principal component regression (PCR) methods was compared. First, the calibration models were built using unnormalised spectra. Next, spectra normalised by the intensity of a selected band of CH(3)CN added as an internal standard to the studied samples were utilised. To compare the predictive ability of the models constructed, the relative standard error of prediction (RSEP) was calculated. The errors found for multivariate calibrations were a few times smaller than those for the univariate ones. Usually, the most effective was the PLS method, for which RSEP values of the order of 1-2% for calibration and 2-3% for testing data sets were obtained. Four commercial preparations of diclofenac sodium and one of aminophylline containing by weight, 2.4% of the active pharmaceutical ingredient (API) were quantified applying the developed models. Concentrations found from the Raman data analysis correlate with the declared values and the results of reference analyses. For the studied diclofenac sodium solutions they amount to 99.2-101.2% of the former and 101.2-102.4% of the latter quantities for the PLS models optimised for each medicine based on unnormalised spectra. These values for the aminophylline preparation were found to be 101.0 and 99.1%, respectively. It shows that the proposed procedure based on the chemometric treatment of FT-Raman spectra can be a fast and convenient alternative to the standard pharmacopoeial procedures of API quantification even in relatively diluted injection solutions.

HPLC determination of aminophylline, methoxyphenamine hydrochloride, noscapine and chlorphenamine maleate in compound dosage forms with an aqueous-organic mobile phase.

A high-performance liquid chromatography procedure for the simultaneous determination of aminophylline, methoxyphenamine hydrochloride, noscapine and chlorphenamine maleate in commercially available compound capsule dosage forms has been developed and validated. The separation and quantification were achieved on an Ultrasphere C18 column using a mobile phase of dichloromethane-methanol-0.25% (v/v) diethylamine aqueous solution (20:60:20, v/v/v) at a flow rate of 1 ml min(-1) with detection of all analytes at 264 nm. The separation was achieved within 6 min for each drug mixture. The method showed good linearity for the aminophylline, noscapine, chlorphenamine maleate and methoxyphenamine hydrochloride mixture in the 125-750, 35-210, 10-60 and 62.5-375 microg ml(-1) ranges, respectively. The intra- and inter-day R.S.D.s ranged from 0.4 to 0.5%, 0.4-0.6%, 0.5-0.7% and 0.4-0.6% for aminophylline, noscapine, chlorphenamine maleate and methoxyphenamine hydrochloride, respectively. The recoveries (mean+/-S.D.) of low, middle and high concentrations were 99.9+/-0.9, 100.4+/-1.3 and 99.7+/-0.7% for aminophylline; 99.9+/-1.1, 100.4+/-0.7 and 100.1+/-0.8% for noscapine; 99.8+/-1.1, 99.7+/-1.0 and 100.7+/-0.8% for chlorphenamine maleate; and 99.8+/-0.9, 100.4+/-1.6 and 99.9+/-0.9% for methoxyphenamine hydrochloride, respectively.

Study on the paper substrate room temperature phosphorescence of theobromine, caffeine and theophylline and analytical application.

Paper substrate room temperature phosphorescence (RTP) of theobromine (TB), caffeine (CF) and theophylline (TP) were investigated. The method is based on fast speed quantitative filter paper as substrate and KI-NaAc as heavy atom perturber. Various factors affecting their RTP were discussed in detail. Under the optimum experimental conditions, the linear dynamic range, limit of detection (LOD), and relative standard deviation (R.S.D.) were 14.41 approximately 576.54 ng per spot, 1.14 ng per spot, 4.8% for TB, 5.44 approximately 699.08 ng per spot, 0.78 ng per spot, 1.56% for CF, 7.21 approximately 360.34 ng per spot, 1.80 ng per spot, 3.80% for TP, respectively. The first analytical application for the determination of these compounds was developed. The recovery of standard samples added to commercial products chocolate, tea, coffee and aminophylline is in the range 92.80-106.08%. The proposed method was successfully applied to real sample analysis without separation.

Kinetic-spectrophotometric determination of theophylline, dyphylline, and proxyphylline by use of partial least-squares regression.

A kinetic-spectrophotometric method for the determination of theophylline, dyphylline and proxyphylline, based on their azo coupling reaction with the diazonium ion of sulfanilic acid after a treatment with alkali, is proposed. The absorbance is recorded from 340 to 600 nm every second during reaction for 90 s, and calibration is performed by partial least-squares regression, using first derivative spectra values. Mixtures containing 2.5-13 micro g mL(-1) dyphylline and proxyphylline, and 2-9 micro g mL(-1) theophylline were successfully resolved with root mean squared errors of prediction (RMSEP) of 0.4, 0.3, and 0.2 for dyphylline, proxyphylline, and theophylline, respectively. The proposed method was satisfactorily applied to the determination of the three compounds in a commercially available pharmaceutical preparation and provided results similar to those obtained by HPLC.

Application of micellar electrokinetic chromatography to the quality control of a pharmaceutical preparation containing three bronchodilators.

Theophylline(1,3-dimethylxanthine), dyphylline [7-(2,3-dihydroxypropyl)theophylline] and proxyphylline [7-(beta-hydroxypropyl)theophylline] are three bronchodilators administered jointly in a single pharmaceutical preparation used against asthma. A micellar electrokinetic chromatography (MEKC) method for their resolution using a background electrolyte consisting of 20 mM tetraborate at pH 8.5 and 100 mM sodium dodecyl sulfate is proposed. The method was used to determine the three active principles in a pharmaceutical preparation. The small amount of sample required and the expeditiousness of the procedure allow content uniformity to be determined in individual tablets. The values of the validation parameters for the method (viz. selectivity, linearity, accuracy, precision, limit of detection, limit of quantitation and robustness) are reported. A complete factor design (2(3)x2) including pH, the surfactant concentration and the ionic strength of the background electrolyte as factors was used to estimate robustness. Based on the results, the method is robust enough for quantitation purposes.

[Preparation and evaluation of alkyl ether-bonded phase for reversed-phase high performance liquid chromatography].

A new silane coupling agent, beta-(3,4-epoxycyclohexyl)ethyltrimethoxy silane, was for the firsty time used to react with octanol, then the intermediate product was coupled onto porous silica to obtain a novel bonded phase for reversed-phase high performance liquid chromatography (RP-HPLC). Characterization of prepared packing was carried out with elemental analysis, solid-state 13C nuclear magnetic resonance spectrometry (NMR), Fourier transform infrared(FT-IR) spectroscopy. Chromatographic evaluations were carried out by using a mixture of organic compounds and methanol-water as the binary mobile phase. The results showed that the stationary phase has excellent chromatographic properties and resist to hydrolysis at a pH value between 2.5 and 7.5. The silanophilic activity of the OEBP was weakened because of the existence of the cyclohexyl group in the packing. It can be efficiently used for the separation of basic compounds.

Aminophylline stability in total parenteral nutrition admixtures.

Aminophylline stability (dose 0.5 and 0.75 g) was estimated in typical AIO nutrient admixtures [Salviamin 12.5% 1000.0 cm3; Glucose 500 g; Intralipid 20% 500.0 cm3; Soluvit N; Vitalipid N Adult; Addamel N; total volume 3000.0 cm3] prepared in DIMIX bags [Diffuplast srl, Italy]. The pH. particle size distribution [Coulter Counter ZM] and theophylline concentration [Spectrophotometer Pye Unicam] were measured immediately after preparation and after 24, 48, 72 hours of storage in low temperature and then after 24 hours in room temperature. Aminophylline proved to be stable in above mentioned doses and now is commonly added into AIO in practice.

[The relationship of the theophylline concentration in the saliva and the blood serum in patients with a broncho-obstructive syndrome]. / Izuchnie sviazi kontsentratsii teofillina v sliune i v syvorotke krovi u bol'nykh s bronkhoobstruktivnym sindromom.

Theophylline salivary and serum concentrations (Tser and Tsal) were quantified after a single dose administration of theophylline drugs: euphylline (2.4% solution, 10 ml i.v. jet and 0.15 orally), theo-dur, retaphil, theopek, theobilong (0.3 g orally). The drugs were given to patients with broncho-obstructive syndrome. The samples were obtained within 6 and 24 hours upon administration for euphylline and other drugs, respectively. Tser and Tsal were determined at high-performance liquid chromatography. The authors revealed a linear relationship between Tser and Tsal in different time intervals. The percentage factors and formulas of Tser calculation by its Tsal values have been estimated.

Dissolution assay of theophylline, diprophylline and proxyphylline from a sustained release dosage form by high performance thin layer chromatography.

The content and dissolution rate of theophylline, diprophylline and proxyphylline from a sustained release formulation were determined by UV in situ densitometry. After separation the chromatographic zones corresponding to the spots of theophylline, diprophylline and proxyphylline on the high performance thin layer chromatographic plates were scanned in reflectance/absorbance mode at 275 nm. Quantification was performed with a second degree polynomial function over the range 40-200 ng for theophylline and 60-300 ng for diprophylline and proxyphylline. Percentages of dissolved theophylline, diprophylline and proxyphylline were monitored over 1, 3 and 6 h. The method was found to be simple, accurate, reliable, time-saving (up to 18 samples can be determined simultaneously) and low-cost.

Effect of retrograde aminophylline administration on calcium and phosphate solubility in neonatal total parenteral nutrient solutions.

The effect of retrograde administration of aminophylline injection on calcium and phosphate solubility in neonatal total parenteral nutrient (TPN) solutions was studied. Neonatal TPN solutions containing two amino acids solutions in three concentrations (Travasol 1% and 2% and TrophAmine 2%) were formulated. Calcium and phosphate salts were added to achieve calcium concentrations of 10, 15, 20, 25, 30, or 40 meq/L and phosphorus concentrations of 10, 15, 20, 25, 30, or 40 mmol/L. Samples were inspected visually after 18-24 hours; solutions free of precipitation were then infused through two parallel syringe-pump systems designed to simulate clinical conditions for TPN solution administration to a 1-kg neonate. To one system, a 7.5-mg aminophylline dose was added as a manual retrograde injection; sterile water for injection was added as a manual retrograde injection to the other system. The solutions were inspected throughout a one-hour infusion period for precipitate formation in the i.v. apparatus, and the pH of the effluents was determined. Concurrent aminophylline administration resulted in visible precipitate in all but a few of the solutions tested. The solution containing Travasol 2%, calcium 10 meq/L, and phosphorus 10 mmol/L remained clear, as did the solutions containing TrophAmine 2% and the following concentrations of calcium and phosphorus: calcium 10 meq/L and phosphorus 10, 15, or 20 mmol/L; calcium 15 meq/L and phosphorus 10 or 15 mmol/L; and calcium 20 meq/L and phosphorus 10 or 15 mmol/L. An average increase in pH of 0.63 unit was noted in all solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of polymeric network structure on drug release from cross-linked poly(vinyl alcohol) micromatrices.

Three types of poly(vinyl alcohol) were cross-linked by glutaraldehyde to form water-swellable materials possessing a three-dimensional, molecular network. Proxyphylline and theophylline were incorporated into the polymer networks during the cross-linking reaction. The firm hydrogels formed were dried and reduced to a particle size of 400-630 microns. The molecular structure of the gels was characterized by equilibrium swelling measurements which allowed the determination of the average distance between two cross-links and, hence, the macromolecular mesh size. The sulfate and glutaraldehyde residues contained in the purified and nonpurified cross-linked polymers were analyzed, and methods for their elimination and inactivation were developed. Drug release from the highly cross-linked gels could be controlled over more than 12 hr, as the diffusion process in these very dense macromolecular networks is rather slow. The extent of branching and entanglement of the polymeric chains appeared to have an important effect. In addition, the release rate was influenced greatly by the amount and, to a lesser extent, by the type of drug in the network.