Formulation development and characterization of liquisolid tablets containing clozapine

L’objectif de ce projet était de développer une formulation liquisolide (LS) de clozapine ayant des propriétés de dissolution améliorées et évaluer sa stabilité et ainsi que sa robustesse à la modification d’excipients. Le propylène glycol (PG), la cellulose microcrystalline (MCC) et le glycolate d’amidon sodique (SSG) ont été utilisés respectivement en tant que véhicule liquide non volatile, agent de masse et agent désintégrant pour la préparation de comprimés LS. Le dioxyde de silicium colloïdal (CSD), le silicate de calcium (CS) et l'aluminométasilicate de magnésium (MAMS) ont été choisis comme agents d’enrobage sec. La caractérisation complète des mélanges et des comprimés a été effectuée. Le taux de libération des comprimés LS était statistiquement supérieur à celui des comprimés réguliers. La surface spécifique des matériaux d’enrobage avait un effet sur les propriétés d’écoulement des mélanges et la taille des particules des matériaux d’enrobage a eu un effet sur la vitesse de dissolution. Le ratio support/enrobage du mélange de poudres (valeur de R) était un paramètre important pour les systèmes LS et devait être plus grand que 20 afin d’obtenir une meilleure libération du médicament. La formulation choisie a démontré une stabilité pour une période d’au moins 12 mois. La technique LS s’est avéré une approche efficace pour le développement de comprimés de clozapine ayant des propriétés de dissolution améliorées. Les comprimés oro-dispersibles (ODT) sont une formulation innovante qui permettent de surmonter les problèmes de déglutition et de fournir un début d'action plus rapide. Dans l’optique d’améliorer les propriétés de dissolution, un essai a été effectué pour étudier la technique LS dans la formulation des ODT de clozapine. Le PG, la MCC, le CSD et la crospovidone (CP) ont été utilisés respectivement en tant que véhicule liquide non volatile, agent de masse, agent d’enrobage sec et agent superdésintégrant pour la préparation de comprimés oro-dispersibles liquisolides (OD-LST). Le mannitol a été choisi comme agent de masse et agent édulcorant. La saccharine de sodium a été utilisée comme agent édulcorant. La caractérisation complète des comprimés a été effectuée. Le taux de libération des OD-LSTs était statisquement supérieur comparativement aux comprimés ODTs. La formulation choisie a démontré une stabilité pour une période d’au moins 6 mois. Il a été conclu que des ODT de clozapine peuvent être préparés avec succès en utilisant la technologie LS dans le but d’améliorer la désintégration et le taux de dissolution de la clozapine dans la cavité orale.

Development and plasticity of locomotor circuits in the zebrafish spinal cord

A fundamental goal in neurobiology is to understand the development and organization of neural circuits that drive behavior. In the embryonic spinal cord, the first motor activity is a slow coiling of the trunk that is sensory-independent and therefore appears to be centrally driven. Embryos later become responsive to sensory stimuli and eventually locomote, behaviors that are shaped by the integration of central patterns and sensory feedback. In this thesis I used a simple vertebrate model, the zebrafish, to investigate in three manners how developing spinal networks control these earliest locomotor behaviors. For the first part of this thesis, I characterized the rapid transition of the spinal cord from a purely electrical circuit to a hybrid network that relies on both chemical and electrical synapses. Using genetics, lesions and pharmacology we identified a transient embryonic behavior preceding swimming, termed double coiling. I used electrophysiology to reveal that spinal motoneurons had glutamate-dependent activity patterns that correlated with double coiling as did a population of descending ipsilateral glutamatergic interneurons that also innervated motoneurons at this time. This work (Knogler et al., Journal of Neuroscience, 2014) suggests that double coiling is a discrete step in the transition of the motor network from an electrically coupled circuit that can only produce simple coils to a spinal network driven by descending chemical neurotransmission that can generate more complex behaviors. In the second part of my thesis, I studied how spinal networks filter sensory information during self-generated movement. In the zebrafish embryo, mechanosensitive sensory neurons fire in response to light touch and excite downstream commissural glutamatergic interneurons to produce a flexion response, but spontaneous coiling does not trigger this reflex. I performed electrophysiological recordings to show that these interneurons received glycinergic inputs during spontaneous fictive coiling that prevented them from firing action potentials. Glycinergic inhibition specifically of these interneurons and not other spinal neurons was due to the expression of a unique glycine receptor subtype that enhanced the inhibitory current. This work (Knogler & Drapeau, Frontiers in Neural Circuits, 2014) suggests that glycinergic signaling onto sensory interneurons acts as a corollary discharge signal for reflex inhibition during movement. v In the final part of my thesis I describe work begun during my masters and completed during my doctoral degree studying how homeostatic plasticity is expressed in vivo at central synapses following chronic changes in network activity. I performed whole-cell recordings from spinal motoneurons to show that excitatory synaptic strength scaled up in response to decreased network activity, in accordance with previous in vitro studies. At the network level, I showed that homeostatic plasticity mechanisms were not necessary to maintain the timing of spinal circuits driving behavior, which appeared to be hardwired in the developing zebrafish. This study (Knogler et al., Journal of Neuroscience, 2010) provided for the first time important in vivo results showing that synaptic patterning is less plastic than synaptic strength during development in the intact animal. In conclusion, the findings presented in this thesis contribute widely to our understanding of the neural circuits underlying simple motor behaviors in the vertebrate spinal cord.

Constructions et représentation de la classe ouvrière du Nord du Québec à Fermont

À l'ère de la mondialisation, où la matrice capitaliste continue de dominer, la classification dans les groupes se définit encore en termes de classes, de genres et d'ethnicité. Les transformations causées par la mondialisation actuelle entraînent de nouveaux modes de production, qui à leur tour transforment les modes de définition et de régulation des populations. Le projet d'exploitation du Nord du Québec est un phénomène relativement récent; or, le processus de construction d'une classe sociale n'est pas un phénomène nouveau. La formation des classes sociales étant toujours en évolution, il semble aujourd'hui pertinent de réexaminer les facteurs économiques, sociologiques et historiques des caractéristiques théoriques nécessaires à la construction et à la représentation d'une classe sociale dont l'existence est liée à l'exploitation accrue des richesses naturelles, la classe ouvrière du Nord du Québec.

 À Fermont, dans le Nord du Québec, les compagnies minières emploient depuis 2011 une grande quantité de travailleurs québécois provenant de l'extérieur de la région, des travailleurs permanents non- résidents. Ainsi, la structure sociale construite sur la force de travailleurs locaux est aux prises avec de nouvelles dynamiques de mobilité sociale géographique. Au travail, les femmes et les autochtones sont aussi affectés par les relations des systèmes de pouvoir de la vie quotidienne, car les emplois de l'industrie minière et du domaine de la construction sont socialement et historiquement fondés sur des capitaux sociaux et culturels (blanc et homme). La classe ouvrière du Nord du Québec est redéfinit par son rapport à la migration géographique des travailleurs permanents non- résidents, par ses relations avec les minorités de genre et les minorités autochtones, relations qui engendrent une organisation sociale complexe et hétérogène.

Development and use of a multiplex real-time quantitative polymerase chain reaction assay for detection and differentiation of Porcine circovirus-2 genotypes 2a and 2b in an epidemiological survey.

By the end of 2004, the Canadian swine population had experienced a severe 2 increase in the incidence of Porcine circovirus-associated disease (PCVAD), a problem that was 3 associated with the emergence of a new Porcine circovirus-2 genotype (PCV-2b), previously 4 unrecovered in North America. Thus it became important to develop a diagnostic tool that could 5 differentiate between the old and new circulating genotypes (PCV-2a and -2b, respectively). 6 Consequently, a multiplex real-time quantitative polymerase chain reaction (mrtqPCR) assay that 7 could sensitively and specifically identify and differentiate PCV-2 genotypes was developed. A 8 retrospective epidemiological survey that used the mrtqPCR assay was performed to determine if 9 cofactors could affect the risk of PCVAD. From 121 PCV-2–positive cases gathered for this 10 study, 4.13%, 92.56% and 3.31% were positive for PCV-2a, PCV-2b, and both genotypes, 11 respectively. In a data analysis using univariate logistic regressions, PCVAD compatible 12 (PCVAD/c) score was significantly associated with the presence of Porcine reproductive and 13 respiratory syndrome virus (PRRSV), PRRSV viral load, PCV-2 viral load, and PCV-2 14 immunohistochemistry (IHC) results. Polytomous logistic regression analysis revealed that 15 PCVAD/c score was affected by PCV-2 viral load (P = 0.0161) and IHC (P = 0.0128), but not by 16 the PRRSV variables (P > 0.9); suggesting that mrtqPCR in tissue is a reliable alternative to IHC. 17 Logistic regression analyses revealed that PCV-2 increased the odds ratio of isolating 2 major 18 swine pathogens of the respiratory tract, Actinobacillus pleuropneumoniae and Streptococcus 19 suis serotypes 1/2, 1, 2, 3, 4, and 7, which are serotypes commonly associated with clinical 20 diseases.

Design, Development & Performance Evaluation of an Anechoic Chamber for

The design, erection and evalution procedures for it microwave anechuic chamber competed at Cochin University for antenna studies are presented the chamber has an average reflectivity level of - 32 dB on at X-band frequencies, and it i, comparable to international standards.

Studies on the Development and Control of Desiccation cracks in compacted clay liner soils

The present study aimed at critically looking at the current practice of the installation of compacted clay liner using bentonite enhanced sand (BES). The application of bentonite is currently the most accepted practice for lining purposes. The ideal bentonite sand combination, which satisfies the liner requirements is 20% bentonite and 80% sand, was selected as one of the liner materials for the investigation of development of desiccation cracks. Locally available sundried marine clay and its combination with bentonite were also included in the study. The desiccation tests on liner materials were conducted for wet/dry cycles to simulate the seasonal variations. Digital image processing techniques were used to measure the crack intensity factor (CIF), a useful and effective parameter for quantification of desiccation cracking. The repeatability of the tests could be well established, as the variation in CIF values of identical samples had a very narrow range of 0 to 2%. The studies on the development of desiccation cracks showed that the CIF of bentonite enhanced sand mixture (BES) was 18.09%, 39.75% and 21.22% for the first, second and third cycles respectively, while it was only 9.83%, 7.52% and 4.58% respectively for sun dried marine clay (SMC). Thus the locally available, alternate liner material suggested, viz SMC, is far superior to BES, when subjected to alternate wet/dry cycles. Further, the improvement of these liner materials when amended with randomly distributed fibre reinforcements was also investigated. Three types of fibres ,namely nylon fibre, polypropylene monofilament and polypropylene fibre mesh were used for the study of fibre amended BES and SMC.The influence of these amendments on the properties of the above liner materials is also studied. The results showed that there is definite improvement in the properties of the liner materials when it is reinforced with discrete random fibres. The study also proved that the desiccation cracks could be controlled with the help of fibre reinforcement.

Development And Analysis Of A Compact Coplanar Antenna With Flared Monopole For Dual Band Applications

Department of Electronics, Cochin University of Science and Technology

DEVELOPMENT AND ANLAYSIS OF BROADBAND L·STRIP FED MICROSTRIP ANTENNAS

The thesis is the outcome of the experimental and theoretical Investigations on novel feeding techniques for bandwidth enhancement of microstrip patches. The new feeding techniques provide bandwidth enhancement without deteriorating the radiation characteristics of the antenna. The antenna is analysed using finite Difference Time Domain (FDTD) method. The predicated results are compared with the experimental results and excellent agreement is observed. The results are also verified using IE3D simulation software. The antenna is suitable for personal and broadband communications.

DEVELOPMENT AND ANALYSIS OF DUAL FREQUENCY MICROSTRIP ANTENNAS

Department of Elecctronics, Cochin University of Science and Technology

Development and Analysis of Microstrip Antennas For Dual Band Microwave Communication

The thesis explores the outcome of the exhaustive theoretical and experimental investigations performed on Octagonal Microstrip Antenna configurations. Development of the MATLAB TM backed 3D-Conformal Finite Difference Time Domain (CFDTD)Modeller for the numerical computation of the radiation characteristics of the antenna is the theme of the work. The predicted results are verified experimentally and by IE3D TM simulation. The influence of the patch dimensions,feed configurations,feed dimensions and feed positions upon the radiation performance of the antenna is studied in detail. Octagonal Microstrip Antenna configurations suitable for Mobile-Bluetooth application is dealt in detail. A simple design formula for the regular Octagonal geometry is also presented. A compact planar multi band antenna for GPS/DCS/2.4/5.8GHz WLAN application is included as appendix A. Planar near field measurement technique is explained in appendix B.

Development and Analysis of a Novel Isosceles Trapezoidal Dielectric Resonator Antenna For Wireless Communication

This thesis describes the development and analysis of an Isosceles Trapezoidal Dielectric Resonator Antenna (ITDRA) by realizing different DR orientations with suitable feed configurations enabling it to be used as multiband, dual band dual polarized and wideband applications. The motivation for this work has been inspired by the need for compact, high efficient, low cost antenna suitable for multi band application, dual band dual polarized operation and broadband operation with the possibility of using with MICs, and to ensure less expensive, more efficient and quality wireless communication systems. To satisfy these challenging demands a novel shaped Dielectric Resonator (DR) is fabricated and investigated for the possibility of above required properties by trying out different orientations of the DR on a simple microstrip feed and with slotted ground plane as well. The thesis initially discusses and evaluates recent and past developments taken place within the microwave industry on this topic through a concise review of literature. Then the theoretical aspects of DRA and different feeding techniques are described. Following this, fabrication and characterization of DRA is explained. To achieve the desired requirements as above both simulations and experimental measurements were undertaken. A 3-D finite element method (FEM) electromagnetic simulation tool, HFSSTM by Agilent, is used to determine the optimum geometry of the dielectric resonator. It was found to be useful in producing approximate results although it had some limitations. A numerical analysis technique, finite difference time domain (FDTD) is used for validating the results of wide band design at the end. MATLAB is used for modeling the ITDR and implementing FDTD analysis. In conclusion this work offers a new, efficient and relatively simple alternative for antennas to be used for multiple requirements in the wireless communication system.

Development and Analysis of Compact AMicrostrip Antennas

The practical applications of microstrip antennas for mobile systems are in portable or pocket-size equipment and in vehicles. Antennas for VHFIUHF handheld portable equipment, such as pagers, portable telephones and transceivers, must naturally be small in size, light in weight and compact in structure. There is a growing tendency for portable equipment to be made smaller and smaller as the demand for personal communication rapidly increases, and the development of very compact hand-held units has become urgent.In this thesis work, main aim is to develop a more and more reduced sized microstrip patch antenna. It is well known that the smaller the antenna size, the lower the antenna efficiency. During the period of work, three different compact circular sided microstrip patches are developed and analysed, which have a significant size reduction compared to standard circular disk antenna (the most compact one of the basic microstrip patch configurations), without much deterioration of its properties like gain, bandwidth and efficiency. In addition to this the interesting results, dual port operation and circular polarization are also observed for some typical designs of these patches. These make the patches suitable for satellite and mobile communication systems.The theoretical investigations are carried out on these compact patches. The empirical relations are developed by modifying the standard equations of rectangular and circular disk microstrip patches, which helps to predict the resonant frequencies easily.

Development and Evaluation of Blind Identification Techniques for Nonlinear Systems

Identification and Control of Non‐linear dynamical systems are challenging problems to the control engineers.The topic is equally relevant in communication,weather prediction ,bio medical systems and even in social systems,where nonlinearity is an integral part of the system behavior.Most of the real world systems are nonlinear in nature and wide applications are there for nonlinear system identification/modeling.The basic approach in analyzing the nonlinear systems is to build a model from known behavior manifest in the form of system output.The problem of modeling boils down to computing a suitably parameterized model,representing the process.The parameters of the model are adjusted to optimize a performanace function,based on error between the given process output and identified process/model output.While the linear system identification is well established with many classical approaches,most of those methods cannot be directly applied for nonlinear system identification.The problem becomes more complex if the system is completely unknown but only the output time series is available.Blind recognition problem is the direct consequence of such a situation.The thesis concentrates on such problems.Capability of Artificial Neural Networks to approximate many nonlinear input-output maps makes it predominantly suitable for building a function for the identification of nonlinear systems,where only the time series is available.The literature is rich with a variety of algorithms to train the Neural Network model.A comprehensive study of the computation of the model parameters,using the different algorithms and the comparison among them to choose the best technique is still a demanding requirement from practical system designers,which is not available in a concise form in the literature.The thesis is thus an attempt to develop and evaluate some of the well known algorithms and propose some new techniques,in the context of Blind recognition of nonlinear systems.It also attempts to establish the relative merits and demerits of the different approaches.comprehensiveness is achieved in utilizing the benefits of well known evaluation techniques from statistics. The study concludes by providing the results of implementation of the currently available and modified versions and newly introduced techniques for nonlinear blind system modeling followed by a comparison of their performance.It is expected that,such comprehensive study and the comparison process can be of great relevance in many fields including chemical,electrical,biological,financial and weather data analysis.Further the results reported would be of immense help for practical system designers and analysts in selecting the most appropriate method based on the goodness of the model for the particular context.

Structure and far-infrared edge modes of quantum antidots at zero magnetic field

We have investigated edge modes of different multipolarity sustained by quantum antidots at zero magnetic field. The ground state of the antidot is described within a local-density-functional formalism. Two sum rules, which are exact within this formalism, have been derived and used to evaluate the energy of edge collective modes as a function of the surface density and the size of the antidot.

Development and Investigations of Mobile Antennas for less Radiation Hazards

Antennas, the key element in wireless communication devices had undergone amazing developments especially in the direction of compactness and safety aspects. In the last two decades, the use of the cellular phones has become the most popular mode of communication across the globe. At the same time, the concerns about the radiation effects have increased in the general public. The main concern of this thesis is to develop a mobile antenna which gives reduced RF interference to the user. The reduction of the power absorbed by the user can tremendously avoid any possible health hazards. The radiation characteristic of a monopole antenna is modified with good radiation characteristics suitable for a mobile handset. The modification is implemented by using different resonating structures which provides reduced radiation along one direction. The direction of less radiation can be changed by modifying the planar antenna structure to a ground folded antenna. This modified structure with excellent radiation characteristic is suitable for modern wireless handheld devices with less user RF interference. Specific Absorption Rate (SAR) is an important parameter for mobile handset. The SAR is estimated for the newly developed antenna for different conditions and discussed in this thesis.