AC biosusceptometry in the study of drug delivery

Conventionally, pharmaceutical substances are administered orally because the gastrointestinal tract possesses the appropriate features for drug absorption. Nevertheless, the gastrointestinal tract physiology is complex and influenced by many factors. These factors must be completely understood for the optimization of oral drug delivery systems. Although in vitro tests provide information about release and drug absorption profiles, in vivo studies are essential, due to the biological variability. Several techniques have been employed in an attempt to conveniently characterize the behavior of solid dosage forms in vivo. The noninvasive biomagnetic technique of alternate current biosusceptometry (ACB) has been used in studies focusing on gastrointestinal motility and, more recently, to evaluate the performance of magnetic dosage forms. This article will discuss the main characteristics of AC biosusceptometry and its applicability for determination of the relationship between the human gastrointestinal tract and orally administered pharmaceutical dosage forms. (c) 2005 Elsevier B.V. All rights reserved.

AC Biosusceptometry as a Tool for Monitoring the Gastrointestinal Transit of Multiparticulate Drug Delivery System

Drug delivery systems based on natural polysaccharides, such as chitosan (CS) and pectin (PC), rather than on synthetic polymers, have been widely studied. Some reasons for that are low toxicity and costs and high biodegradability of the formers. A multiparticulate system based on CS and PC was developed in our laboratories, including the addition of an enteric polymer, cellulose acetate phtalate (CAP). Such improvement promoted stronger gastric and enteric resistances, as assessed in vitro, making the systems more selective to enzymatic degradation in the colon. Although in vitro dissolution tests can simulate some properties concerning the gastrointestinal transit (GT), collaborating to characterize the systems behavior in the biological fluids, frequently they do not result in satisfactory in vitro/in vivo correlations. The objective of this work was to follow in vivo the GT of the particles developed by means of AC biosusceptometry (ACB), a non-invasive and of low cost methodology. The particles containing ferrite in powder form were prepared by complex coacervation using an ideal 3:1:1 mass ratio for PC:CS:CAP. The magnetic particles were administered to healthy volunteers by oral route. The GT was monitored by using multi-sensor ACB system and the signal acquisition was performed every IS min until the colonic region was reached. By means of ACB technique, it was possible to acquiring images generated by the magnetic particles within the whole gastrointestinal tract including the colonic region. Variable particles transit times were observed among the volunteers, but without interference on the mapping of the particles until the colonic region. The particles were able to produce magnetic field strong enough to generate signals adequate for mapping the particles. The results suggest that integral particles reached the colon, after they resisted against gastric and enteric media. Studies associating transit time and in vivo drug release are in development in order to confirm the efficiency of the systems.

Analysis of the E-J Curve of HTS Tapes Under DC and AC Magnetic Fields at 77 K

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

DC and AC side harmonics in CCC converters

The capacitor-commutated converter (CCC) has frequently been used in the conception of HVDC systems connected to busbars with low short circuit level. This alternative arrangement, in substitution to the conventional ones, guarantees less sensitive operational conditions to problems related with the commutation failure in the inverters besides supplying part of the reactive energy to be compensated. Studies related with its performance in steady and transient states have been presented in several works, however its behavior as harmonic source is still little explored. This work presents preliminary studies focusing the generation of characteristic harmonics by this type of converter. Subjects related with the amplification of the harmonic magnitudes are investigated and compared considering similar arrangements of conventional static converters (LCC) and CCC schemes. It is also analyzed the harmonic generation on the dc side of the installation and its influence on the ac side harmonics. The results are obtained from simulations in the time domain in PSpice environment and they clearly illustrate the operational differences between the L CC and the CCC schemes with regard to characteristic harmonic generation.

DCM Boost interleaved converter for operation in AC and DC to trolleybus application

This paper is based on the development and experimental analysis of a DCM Boost interleaved converter suitable for application in traction systems of electrical vehicles pulled by electrical motors (Trolleybus), which are powered by urban DC or AC distribution networks. This front-end structure is capable of providing significant improvements in trolleybuses systems and in the urban distribution network costs, and efficiency. The architecture of proposed converter is composed by five boost power cells in interleaving connection, operating in discontinuous conduction mode. Furthermore, the converter can operate as AC-DC converter, or as DC-DC converter providing the proper DC output voltage range required by DC or AC adjustable speed drivers. Therefore, when supplied by single-phase AC distribution networks, and operating as AC-DC converter, it is capable to provide high power factor, reduced harmonic distortion in the input current, complying with the restrictions imposed by the IEC 61000-3-4 standards. The digital controller has been implemented using a low cost FPGA and developed totally using a hardware description language VHDL and fixed point arithmetic. Thus, two control strategies are evaluated considering the compliance with input current restrictions imposed by IEC 61000-3-4 standards, the regular PWM modulation and a current correction PWM modulation. In order to verify the feasibility and performance of the proposed system, experimental results from a 15 kW low power scale prototype are presented, operating in DC and AC conditions.

Efficient method for AC transmission network expansion planning

A combinatorial mathematical model in tandem with a metaheuristic technique for solving transmission network expansion planning (TNEP) using an AC model associated with reactive power planning (RPP) is presented in this paper. AC-TNEP is handled through a prior DC model while additional lines as well as VAr-plants are used as reinforcements to cope with real network requirements. The solution of the reinforcement stage can be obtained by assuming all reactive demands are supplied locally to achieve a solution for AC-TNEP and by neglecting the local reactive sources, a reactive power planning (RPP) will be managed to find the minimum required reactive power sources. Binary GA as well as a real genetic algorithm (RCA) are employed as metaheuristic optimization techniques for solving this combinatorial TNEP as well as the RPP problem. High quality results related with lower investment costs through case studies on test systems show the usefulness of the proposal when working directly with the AC model in transmission network expansion planning, instead of relaxed models. (C) 2010 Elsevier B.V. All rights reserved.

Mesoscopic structure evidenced by AC dielectric nonlinearities in Sr(0.75)Ba(0.25)Nb(2)O(6) relaxor ferroelectric thin films

The AC electric field and temperature dependences of the dielectric permittivity for strontium barium niobate (Sr(0.75)Ba(0.25)Nb(2)O(6)) relaxor ferroelectric thin films have been investigated. The results indicate the existence of a true mesoscopic structure evidenced by the nonlinear dielectric response of these films, which is similar to those observed for bulk relaxor ferroelectrics. A tendency for a temperature dependent crossover from a linear to a quadratic behaviour of the dielectric nonlinearity was observed, indicating an evolution from paraelectric to glass-like behaviour on cooling the samples towards the freezing temperature transition.

AC Conductivity and Impedance Properties of 0.65Pb(Mg1/3Nb2/3)O-3-0.35PbTiO(3) Ceramics

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Scintigraphic validation of AC Biosusceptometry to study the gastric motor activity and the intragastric distribution of food in humans

Abnormal intragastric distribution of food (IDF) and a phasic contractility in the proximal stomach have been related to dyspeptic symptoms. Thus, the behaviour of the stomach and the proximal region, in particular, continues to attract attention and demand for reliable and comfortable techniques. The aims of this study were to employ AC Biosus-ceptometry (ACB) and scintigraphy to evaluate IDF and gastric motor activity in humans. Fifteen healthy volunteers ingested 60 mL of yogurt containing 2 mCi of Tc-99m and 4 g of ferrite. Each volunteer had gastric motility and IDF evaluated twice on separate days; on one occasion by ACB and another by scintigraphy. Digital signal processing was performed in MatLab (Mathworks Inc., Natick, MA, USA). Results were expressed as mean +/- SD. Similar results of distal accumulation time (P < 0.001) were obtained for scintigraphy (6.93 +/- 3.25 min) and for ACB (7.04 +/- 3.65 min). Fast Fourier Transform revealed two dominant frequencies (P > 0.9). Besides the well-know frequency of 3 cpm, our results showed identical frequencies in proximal stomach recordings (P < 0.001) for scintigraphic (1.01 +/- 0.01 cpm) and ACB (0.98 +/- 0.06 cpm). In summary, our data showed that scintigraphy and ACB are promising techniques to evaluate several aspects of gastric motility. Moreover, ACB is non-invasive, radiation-free and deserves the same importance as conventional methods for this kind of analysis.

Magnetic images of the disintegration process of tablets in the human stomach by ac biosusceptometry

Oral administration of solid dosage forms is usually preferred in drug therapy. Conventional imaging methods are essential tools to investigate the in vivo performance of these formulations. The non-invasive technique of ac biosusceptometry has been introduced as an alternative in studies focusing on gastrointestinal motility and, more recently, to evaluate the behaviour of magnetic tablets in vivo. The aim of this work was to employ a multisensor ac biosusceptometer system to obtain magnetic images of disintegration of tablets in vitro and in the human stomach. The results showed that the transition between the magnetic marker and the magnetic tracer characterized the onset of disintegration (t(50)) and occurred in a short time interval (1.1 +/- 0.4 min). The multisensor ac biosusceptometer was reliable to monitor and analyse the in vivo performance of magnetic tablets showing accuracy to quantify disintegration through the magnetic images and to characterize the profile of this process.

Gastrointestinal transit and disintegration of enteric coated magnetic tablets assessed by ac biosusceptometry

The oral administration is a common route in the drug therapy and the solid pharmaceutical forms are widely used. Although much about the performance of these formulations can be learned from in vitro studies using conventional methods, evaluation in vivo is essential in product development. The knowledge of the gastrointestinal transit and how the physiological variables can interfere with the disintegration and drug absorption is a prerequisite for development of dosage forms. The aim of this work was to employing the ac biosusceptometry (ACB) to monitoring magnetic tablets in the human gastrointestinal tract and to obtain the magnetic images of the disintegration process in the colonic region. The ac biosusceptometry showed accuracy in the quantification of the gastric residence time, the intestinal transit time and the disintegration time (DT) of the magnetic formulations in the human gastrointestinal tract. Moreover, ac biosusceptometry is a non-invasive technique, radiation-free and harmless to the volunteers, as well as an important research tool in the pharmaceutical, pharmacological and physiological investigations. (c) 2005 Elsevier B.V. All rights reserved.

Enteric coated magnetic HPMC capsules evaluated in human gastrointestinal tract by AC biosusceptometry

Purpose. To employ the AC Biosusceptometry (ACB) technique to evaluate in vitro and in vivo characteristics of enteric coated magnetic hydroxypropyl methylcellulose (HPMC) capsules and to image the disintegration process.Materials and Methods. HPMC capsules filled with ferrite (MnFe2O4) and coated with Eudragit (R) were evaluated using USP XXII method and administered to fasted volunteers. Single and multisensor ACB systems were used to characterize the gastrointestinal (GI) motility and to determine gastric residence time (GRT), small intestinal transit time (SITT) and orocaecal transit time (OCTT). Mean disintegration time (t (50)) was quantified from 50% increase of pixels in the imaging area.Results. In vitro and in vivo performance of the magnetic HPMC capsules as well as the disintegration process were monitored using ACB systems. The mean disintegration time (t (50)) calculated for in vitro was 25 +/- 5 min and for in vivo was 13 +/- 5 min. In vivo also were determined mean values for GRT (55 +/- 19 min), SITT (185 +/- 82 min) and OCTT (240 +/- 88 min).Conclusions. AC Biosusceptometry is a non-invasive technique originally proposed to monitoring pharmaceutical dosage forms orally administered and to image the disintegration process.

AC Biosusceptometry Technique to Evaluate the Gastrointestinal Transit of Pellets under Influence of Prandial State

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pharmaceutical applications of AC Biosusceptometry

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Measurement of gastric contraction activity in dogs by means of AC biosusceptometry

The mechanical nature of gastric contraction activity (GCA) plays an important role in gastrointestinal motility. The aim of this study was to detect GCA in anaesthetized dogs, using simultaneously the techniques of AC biosusceptometry (ACB) and manometry, analysing the characteristics of frequency and amplitude (motility index) of GCA, modified by drugs such as prostigmine and N-butyl-scopolamine. The ACB method is based on a differential transformer of magnetic flux and the magnetic tracer works as a changeable external nucleus. This magnetic tracer causes a modification in the magnetic flux, which is detected by the coils. The results obtained from the ACB showed a performance comparable to the manometry in measuring the modifications in the frequency and amplitude of the GCA. We concluded that this ACB technique, non-invasive and free of ionizing radiation, is an option for evaluating GCA and can be employed in future clinical studies.