RESUMO
Graphene nanopores are receiving great attention due to their atomically thin membranes and intrinsic electrical properties that appear greatly beneficial for biosensing and DNA sequencing. Here, we present an extensive study of the low-frequency 1/f noise in the ionic current through graphene nanopores and compare it to noise levels in silicon nitride pore currents. We find that the 1/f noise magnitude is very high for graphene nanopores: typically two orders of magnitude higher than for silicon nitride pores. This is a drawback as it significantly lowers the signal-to-noise ratio in DNA translocation experiments. We evaluate possible explanations for these exceptionally high noise levels in graphene pores. From examining the noise for pores of different diameters and at various salt concentrations, we find that in contrast to silicon nitride pores, the 1/f noise in graphene pores does not follow Hooge's relation. In addition, from studying the dependence on the buffer pH, we show that the increased noise cannot be explained by charge fluctuations of chemical groups on the pore rim. Finally, we compare single and bilayer graphene to few-layer and multi-layer graphene and boron nitride (h-BN), and we find that the noise reduces with layer thickness for both materials, which suggests that mechanical fluctuations may be the underlying cause of the high 1/f noise levels in monolayer graphene nanopore devices.
Assuntos
Técnicas Biossensoriais/métodos , Grafite/química , Nanopartículas Metálicas/química , Nanoporos , Nanotecnologia/métodos , Benzofenonas , Soluções Tampão , DNA/química , Etanol/química , Análise de Fourier , Concentração de Íons de Hidrogênio , Cetonas/química , Microscopia Eletrônica de Transmissão , Polietilenoglicóis/química , Polímeros , Reprodutibilidade dos Testes , Análise de Sequência de DNA , Razão Sinal-RuídoRESUMO
On the basis of biopharmaceutic-pharmacokinetic and galenic aspects a new sustained-release preparation of theophylline according to the "divided-dose" principle was developed. The technological procedure used allows a reproducible manufacture of a stable product with narrow limits of pharmaceutical quality. The bioavailability of the sustained-release pellets in a dose corresponding to 350 mg active principle is examined in comparison to an aqueous solution or retard-tablet formulation on the marked (containing 260 mg drug/dose), respectively, after single or multiple dose administration to 7 healthy volunteers. The relative bioavailability of the new formulation is about 100%. During chronic application the controlled drug delivery from the sustained-release pellets warrants only slight fluctuations of plasma levels by avoiding peak concentrations. Formulations with a dosage of 200, 350 or 500 mg, respectively, allow adaptation of continuous plasma levels in the therapeutic range between 5--20 micrograms/ml according to the therapeutic necessities of a patient.
Assuntos
Teofilina/administração & dosagem , Adulto , Disponibilidade Biológica , Preparações de Ação Retardada , Estabilidade de Medicamentos , Humanos , Cinética , Masculino , Modelos Biológicos , Teofilina/metabolismo , Fatores de TempoRESUMO
A method is described which allows the oral administration of drugs in solid form by hardgelatin mini-caps to rats with a simple device. The method is especially suitable for the administration of solid, radioactively labelled drugs.
Assuntos
Administração Oral/veterinária , Preparações Farmacêuticas/administração & dosagem , Animais , Cápsulas , Equipamentos e Provisões , Métodos , RatosAssuntos
Alcanossulfonatos , Benzilatos , Cinética , Octanóis , Solubilidade , Relação Estrutura-Atividade , ÁguaRESUMO
Distribution studies in vitro predict increasing absorption rates in vivo with increasing distribution coefficients up to a limiting value. Buccal absorption tests with homologous, quaternary cholinesterbromides of benzilic acid do not confirm this hypothesis. The reasons could be the rather hydrophilic properties of the mucosal membranes and thus adsorption of drug to the mucosa. The evaluation of results with undissociated homologous carboxylic acids, however, shows a good correlation between the prediction from in vitro studies and the buccal absorption test.
Assuntos
Benzilatos/metabolismo , Mucosa Bucal/metabolismo , Compostos de Amônio Quaternário/metabolismo , Absorção , Difusão , Ésteres , Humanos , Lipídeos de Membrana , Membranas Artificiais , Modelos TeóricosRESUMO
The addition of NaBr, Na-butansulfonate or Na-trichloracetat increases the partition coefficients of homologous quaternary cholinesters of benzilic acid between n-octanol and water. In a three-phase model (water/n-octanol/water) thus the rates of equilibration increase considerably for hydrophilic compounds.
Assuntos
Benzilatos , Compostos de Amônio Quaternário , Brometos , Butanos , Fenômenos Químicos , Físico-Química , Difusão , Cinética , Octanóis , Solubilidade , Relação Estrutura-Atividade , Ácidos Sulfônicos , Propriedades de Superfície , Fatores de Tempo , Ácido TricloroacéticoRESUMO
The partition of homologous quaternary esters of benzilic acid is studied in a modified three-phase model according to Schulmann (water-n-octanol-water). The logarithms of the partition coefficients of the compounds increase linearly with increasing alkyl chain. The rate determining step for the interphase transport of hydrophilic compound is the diffusion through the organic diffusion layer. The rate constants for the transfer from the aqueous to the organic phase increase linearly with the corresponding partition coefficient, whereas the rate constants for the reverse reaction are not influenced. With increasing chain length the diffusion through the aqueous diffusion layer becomes rate determining for the interphase transport. Thus the rate constants for the transfer from the aqueous to the organic phase are independent of partition coefficients. The rate constants for the reverse transfer are inversely proportional to the corresponding partition coefficients. The half-lives of the transfer of the homologous compounds under sink conditions show a minimum between the heptyl and octyl derivative. The equilibration time decreases with increasing agitation, concentration and temperature. The significance of the results for biological problems is discussed.