Hydrophilic polymers in a swellable matrix tablet hydrate quickly to form a hydrogel layer on the exterior of the dosage once in contact with water or biologic fluid. The resultant hydrogel serves as a barrier to regulate water permeation into the matrix and drug diffusion from the preparation. It is therefore important to understand how the polymer is hydrated and what mechanism exists between hydrogel formation and drug dissolution from a swellable matrix tablet. In this thesis, a TA texture analyzer was utilized to monitor and characterize matrix swelling properties during dissolution process. Multiple regression models were employed to analyze the quantitative relationship between drug dissolution or hydrogel thickness and major formulation factors (polymer ratio, drug solubility). Modified release matrix tablets were prepared using four APIs with a range of aqueous solubility, i.e., acetaminophen (ACE), chlorpheniramine (CHL), ibuprofen (IBU), and pseudoephedrine hydrochloride (PSE). Two hydrophilic polymers, polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) were selected and tested as primary matrix polymers for the formulations. It was found from the experiments that multiple regression model was capable of estimating drug dissolution for both PEO and HPMC matrix preparations. Based on major formulation factors the regression models provide satisfactory prediction of drug release, which could further aid in formulation development and optimization.

Hydrophilic polymers in a swellable matrix tablet hydrate quickly to form a hydrogel layer on the exterior of the dosage once in contact with water or biologic fluid. The resultant hydrogel serves as a barrier to regulate water permeation into the matrix and drug diffusion from the preparation. It is therefore important to understand how the polymer is hydrated and what mechanism exists between hydrogel formation and drug dissolution from a swellable matrix tablet. In this thesis, a TA texture analyzer was utilized to monitor and characterize matrix swelling properties during dissolution process. Multiple regression models were employed to analyze the quantitative relationship between drug dissolution or hydrogel thickness and major formulation factors (polymer ratio, drug solubility). Modified release matrix tablets were prepared using four APIs with a range of aqueous solubility, i.e., acetaminophen (ACE), chlorpheniramine (CHL), ibuprofen (IBU), and pseudoephedrine hydrochloride (PSE). Two hydrophilic polymers, polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) were selected and tested as primary matrix polymers for the formulations. It was found from the experiments that multiple regression model was capable of estimating drug dissolution for both PEO and HPMC matrix preparations. Based on major formulation factors the regression models provide satisfactory prediction of drug release, which could further aid in formulation development and optimization.

Ce travail concerne l'étude du comportement rhéologique de nanocomposites modèles à base de Laponite dans du polyoxyde d'éthylène ou des mélanges polyoxyde d'éthylène avec du polyméthacrylate de méthyle. L'influence des paramètres moléculaires, masse molaire de la matrice et mode de protection des particules sur les propriétés rhéologiques a été étudiée. La meilleure dispersion est obtenue à partir d'une solution, la dilution d'un mélange maître conduisant à des matériaux hétérogènes. Les mélanges POE/PMMA sont compatibles à l'état fondu dans toute la gamme de concentrations mais hétérogènes à température ambiante au-dessus de 30% en poids de particules. En diluant un mélange Laponite/PEO dans le PMMA, nous avons montré que ces domaines se concentrent en particules en dessous de 30% de PEO et qu'une cocontinuité de phases PEO contenant les particules et PMMA essentiellement pur est formée au-dessus de 30% de PEO. La présence des particules diminue fortement la cristallinité. / This study concerns model nanocomposites based on Laponite and polyethylene oxide, alone or blended with polymethylmethacrylate. We studied the influence of the parameters on rheological properties of model PEO/Laponite nanocomposites such as matrix molecular weight, preparation method. The best dispersion state of the particles is obtained from solution. Melt dispersion leads to a low frequency modulus which depends on the length and grafting density of the particles. Heterogeneous materials are obtained from melt dispersion of a master batch. PMMA/PEO blends appear to be homogeneous at room temperature only for PEO concentration less than 30wt%. Laponite particles are concentrated in small domains where most of PEO has been extracted. At higher concentrations of PEO, a continuous phase containing PEO and Laponite above percolation concentration is observed, leading to an elastic modulus at low frequency. The presence of Laponite decreases significantly the crystallinity of PEO.

De nouvelles familles de liquides ioniques conducteurs par ion lithium; à anions aromatiques et aliphatiques de type perfluorosulfonate perfluorosulfonylimidure attachés à des oligoéthers (méthoxy polyéthylène glycol mPEG) de longueurs différentes ont été synthétisées et caractérisées dans le but d'améliorer l'interaction entre les chaînes de POE et les sels de lithium en améliorant la mobilité segmentaire. Ainsi différentes membranes amorphes ou peu cristallines améliorent le transport cationique par rapport aux électrolytes polymères usuels. . Leurs propriétés ont été évaluées dans deux types de polymères hôtes : un polyéther linéaire (POE) et un polyéther réticulé préparé par un procédé "VERT". Leurs parties oligooxyéthylène aident à la solvatation des cations lithium et conduisent à l'augmentation des propriétés de transport; c'est à dire la conductivité cationique et le nombre de transport. Leurs stabilités thermiques et électrochimiques sont adaptées à l'application batterie lithium-polymère. / The new families of lithium-conducting ionic liquids; aromatic and aliphatic lithium salts based on perfluorosulfonate and perfluorosulfonylimide anions attached to an oligoether (methoxy polyethylene glycol mPEG) with different lengths were synthesized and characterized with the aim to improve the salt interaction with the host polymer's POE chains while keeping a high segmental mobility. They allowed obtaining membranes with lower crystallization degree and higher cationic transport number as compared with benchmarked salts. Their properties as lithium salts were investigated in two types of host polymers i.e. a linear polyether (POE) and a cross-linked polyether prepared by a ‘GREEN' process. Their oligooxyethylene moieties improve the lithium cation solvation leading to an increase in cationic transference numbers. Their electrochemical and thermal stabilities are suitable for lithium battery application.

De nouvelles familles de liquides ioniques conducteurs par ion lithium; à anions aromatiques et aliphatiques de type perfluorosulfonate perfluorosulfonylimidure attachés à des oligoéthers (méthoxy polyéthylène glycol mPEG) de longueurs différentes ont été synthétisées et caractérisées dans le but d'améliorer l'interaction entre les chaînes de POE et les sels de lithium en améliorant la mobilité segmentaire. Ainsi différentes membranes amorphes ou peu cristallines améliorent le transport cationique par rapport aux électrolytes polymères usuels. . Leurs propriétés ont été évaluées dans deux types de polymères hôtes : un polyéther linéaire (POE) et un polyéther réticulé préparé par un procédé "VERT". Leurs parties oligooxyéthylène aident à la solvatation des cations lithium et conduisent à l'augmentation des propriétés de transport; c'est à dire la conductivité cationique et le nombre de transport. Leurs stabilités thermiques et électrochimiques sont adaptées à l'application batterie lithium-polymère. / The new families of lithium-conducting ionic liquids; aromatic and aliphatic lithium salts based on perfluorosulfonate and perfluorosulfonylimide anions attached to an oligoether (methoxy polyethylene glycol mPEG) with different lengths were synthesized and characterized with the aim to improve the salt interaction with the host polymer's POE chains while keeping a high segmental mobility. They allowed obtaining membranes with lower crystallization degree and higher cationic transport number as compared with benchmarked salts. Their properties as lithium salts were investigated in two types of host polymers i.e. a linear polyether (POE) and a cross-linked polyether prepared by a ‘GREEN' process. Their oligooxyethylene moieties improve the lithium cation solvation leading to an increase in cationic transference numbers. Their electrochemical and thermal stabilities are suitable for lithium battery application.

Electrospinning, un procédé original de mise en forme de polymère par application d'un champ électrique élevé, est largement utilisé pour la synthèse de membranes non tissées nanofibreuses. Les membranes électrospinnées ont une forte porosité et un rapport surface / volume élevé. En effet, ces matériaux ont suscité beaucoup d'intérêt et d'études au cours des dernières décennies, ce qui ouvre la voie à de nombreuses applications telles que la détection, l'ingénierie tissulaire ou la livraison de médicaments. La recherche actuelle vise à avoir des membranes fibreuses avec une architecture contrôlée utilisant différents types de collecteurs.Le développement de nanofibres à base de biopolymères et une stratégie thérapeutique pour la régénération des tissus mous.Le premier objectif de cette thèse était de développer de nouveaux matériaux biocompatibles et bio résorbables à l'aide de fibres à l'échelle nanométrique obtenues par électrospinning. En outre, cette étude a examiné l'influence de la viscosité, de la concentration et de la tension superficielle des solutions de polymère sur les fibres obtenues. En outre, le débit, la tension appliquée et les paramètres environnementaux (température et humidité) ont également été optimisés au cours de la production de nanofibres.Les fibres ont été obtenues à partir de PEO, polymère biocompatible. C'est un polymère linéaire qui se compose de segments éthylène et éther [-CH2CH2O-]n. L'oxyde d'éther peut être utilisé pour interagir avec des espèces hydrophiles. En raison de sa solubilité dans l'eau, sa non-toxicité et sa capacité à être électrospinné, le PEO a été utilisé comme additif dans des solutions de biopolymères pour permettre la formation d'électrodes fibreuses. La résistance mécanique du PEO dépend de la masse moléculaire, de la conformation des chaînes polymères et de la taille des fibres ainsi que la structure du réseau.Le deuxième effort majeur de cette thèse s'est concentré sur le contrôle des mailles fibreuses. Une telle activité de recherche est justifiée par l'influence attendue de la morphologie du réseau de fibres sur les propriétés mécaniques des membranes et leur caractère biomimétique qui favorise la colonisation et la croissance des cellules du tissu hôte. Le contrôle de cette structure a été réalisé grâce au développement de collecteurs.L'objectif de la thèse est de fabriquer des structures fibreuses non tissées aléatoires et structurées par electrospinning. Ces structures fibreuses sont obtenues à partir de Poly (oxyde d'éthylène), PEO, en solutions à différentes concentrations et masses moléculaires.Le dépôt de fibres est réalisé sur deux types de collecteurs: a) Feuille d'aluminium, b) Collecteur micro-structuré (dimension 3 × 3 cm). Les analyses morphologiques des membranes ont été menées à l'aide d'une microscopie électronique à balayage (MEB) et leurs propriétés mécaniques sous traction ont été réalisées à l'aide du rhéomètre ARESG2.La morphologie des matériaux electrospinnées passe graduellement d'une structure de type perles à des fibres uniformes lorsque la concentration et la masse moléculaire augmentent. Une étude comparative des propriétés morphologiques et mécaniques (essai de traction) des deux structures fibreuses a été réalisée. Cette étude a montré qu'il est possible d'avoir une distribution de fibres formant une cellule primitive très uniforme dans un réseau de dimension 3 × 3 cm. Ce réseau structuré a une contrainte à la rupture plus importante que celle du réseau fibreux aléatoire obtenu conventionnellement avec une feuille d'aluminium. / Electrospinning, an original polymer process under high electric fields to produce a network of thin fiber having a micrometer diameter, is widely used for the synthesis of nanofibrous non-woven membranes. The fabricated electrospun membranes have a high porosity and a high surface to volume ratio. Indeed, they reveal much interest and have been much developed in the last decades, which paves the way for numerous applications such as sensing, tissue engineering or drug delivery. Current research aims to have fibrous membranes with a controlled architecture using various types of collectors.This thesis is part of a global and emerging project that focuses on the production of structured scaffolds nanofibers based on biopolymers and dedicated to the therapeutic strategy for the regeneration of soft tissues.In the present work, the first focus was to develop new biocompatible and bioresorbable materials composed of nanoscale fibers obtained by electrospinning. In addition, this study examined the influence of viscosity, concentration, and surface tension of PEO solutions on the obtained fibers. Further, the flow rate, applied voltage and environmental parameters (temperature and humidity) were also optimized in the course of nanofibers production.Biocompatible fibers have been obtained by using PEO. It is a linear polymer that consists of ethylene and ether segments [-CH2CH2O-]n. The ether oxygen allows this polymer to interact with other hydrophilic species, while the ethylene part participates in hydrophobic interactions. Due to its water solubility, non-toxicity and electrospinn ability, PEO has been used as an additive in biopolymer solutions to enable the formation of electrospun fibers. The mechanical strength of the PEO depended on the molecular weight, the conformation of the polymer chains and the fiber scale, the structure of the network.The second major effort of this thesis focused on the control of the mesh fibers. Such research activity is justified by the expected influence of the morphology of the fiber network on the mechanical properties of scaffolds and their biomimetic character that could favor the colonization and growth of the cells of the host tissue. The control of this structure has been achieved through the development of collectors.The objective of this project is making non-woven fibrous structures in uncontrolled architecture as well as non-woven with controlled architecture by using the electrospinning process. These fibrous structures are obtained from Poly(ethylene oxide), PEO, solutions with different concentration and molecular weight. The deposit of fibers is made on two types of collectors: a) Aluminum foil, b) micro-structured collector (dimension 3×3 cm). The morphological analyses of the membranes were investigated using scanning electron microscopy (SEM) and their mechanical properties were characterized by tensile test using the ARESG2 rheometer. The morphology of the electrospun polymer gradually changes from beads to uniform fibers with increasing polymer concentration and molecular weight. A comparative study of the morphological and mechanical (tensile test) properties, of both fibrous structures is performed. This study showed that it is possible to have a distribution of fiber forming a very uniform primitive cell in a network of dimension 3×3 cm. This structured network has a strain at the break more important than that for the network fibers, which are collected on Aluminum foil.

Dans le but de développer des matériaux actifs antimicrobiens biodégradables à libération contrôlée, des mélanges de deux polymères biodégradables incompatibles ont été mis en oeuvre par les voies classiques de transformation des matériaux plastiques (extrusion). L'originalité de ces mélanges réside dans la recherche d'une stratégie de contrôle de la libération d'espèces actives incorporées dans l'une des phases du système et générée par la tortuosité/disponibilité de chemins de diffusion sélectifs obtenue en jouant sur les proportions relatives des 2 polymères en présence. Les systèmes binaires étudiés sont : [amidon de maïs plastifié, PLS et poly(butylène succinate-co-adipate) ou PBSA] et un système référence [(poly(oxyethylène) PEO et PBSA]. Dans ces mélanges, les polymères polaires (PLS ou PEO) jouent le rôle de matrice hôte pour solubiliser les migrants actifs ou modèles, souvent polaires et le polymère semipolaire,le PBSA, compense la faiblesse des propriétés mécaniques et barrières à l'eau de la phase amylacée et /ou hydrophile tout en présentant une température de fusion basse (85°C) compatible avec une stratégie à plus long terme d'incorporation d'actifs peu thermostables. Les systèmes obtenus sont caractérisés afin de corréler les différentes morphologies obtenues en jouant sur la composition des mélanges (phase dispersées dans une matrice continue, ou continuité partielle ou totale, systèmes pseudo-multicouches) aux phénomènes de transport de diverses molécules. Les caractérisations effectuées ont alors pour objectif d'élucider les morphologies obtenues par i) extraction sélective par voie solvant (ou hydrolyse) enrichie par des observations microscopiques ii) par utilisation de sondes gazeuses via les propriétés de transport de vapeur d'eau (qui privilégiera les chemins offerts par la matrice polaire) ou de l'oxygène (qui, lui, privilégiera les chemins de diffusions offerts par le PBSA) iii) par la réalisation des isothermes et cinétiques de sorption d'eau et enfin iv) par l'étude de la libération dans l'eau de migrants actifs ou modèles préalablement incorporés dans la phase polaire (fluorescéinate de sodium, acides organiques, glycine, di-glycine). Il a ainsi pu être montré pour les mélanges PLS/PBSA que les phénomènes de diffusion sont contrôlés par la tortuosité générée par la présence de PBSA dans le cas du relargage de la fluorescéine et par l'hydratation limitée de la phase polaire en présence de fortes teneurs en PBSA dans le mélange pour les phénomènes de sorption d'eau. Ainsi, la diffusion de la fluorescéine, par exemple, est nettement plus influencée que celle de l'eau par la tortuosité (elle-même gouvernée par la composition du mélange), très probablement en raison de sa plus grande masse moléculaire. Pour les mélanges PEO/PBSA, des comportements distincts ont été mis en évidence selon la composition des mélanges. Pour les mélanges à faibles teneurs ou teneurs intermédiaires en PBSA, un transport rapide se produit principalement via la dissolution du PEO. La morphologie ne semble pas influencer les cinétiques de libération. Pour des teneurs élevées en PBSA, la cinétique de libération est cette fois dépendante de la morphologie présente un temps de latence caractéristique d'une cinétique de perméation (libération proportionnelle au temps). En conclusion, les matériaux élaborés par les voies migrants polaires tels que des conservateurs pour élaborer par exemple des emballages actifs antimicrobiens / In order to develop biodegradable and active materials s, blends of two incompatible biodegradable polymers have been implemented by conventiona plastic material processing (extrusion). The originality of these blends lies in the search for a strategy to control the release of active species included in one of the phases of the system. Therefore, the tortuosity / availability of selective diffusion paths obtained by varying the relative proportions of the two polymers involved will be exploited. Studied binary systems consist of: [plasticized corn starch, PLS and poly (butylene succinate-co-adipate) or PBSA] and a reference system [(poly (oxyethylene) PEO and PBSA]. In these blends, polar polymers (PLS or PEO) play the role of host matrix to solubilize the active migrants or model molecules which are often polar, and the semi-polar polymer (PBSA) compensates for the weakness of the mechanical properties of the starchy and / or hydrophilic phase while having a low melting temperature (85 ° C) consistent with a longer-term strategy of incorporation of thermostable active molecules such as lysozyme or nisin. The resulting systems were characterized to correlate the different morphologies obtained by varying the composition of the blends (dispersed phase in a continuous matrix, partial or total continuity, or pseudo-layer systems) to the transport phenomena of various molecules. The performed characterizations aim to elucidate the morphologies by i) selective solvent extraction method (or hydrolysis) enriched by microscopical observations ii) using gaseous probes via the determination of water vapor transport properties (water will favor the paths provided by the polar matrix) or oxygen transport properties (O2 will favor the diffusion paths provided by the PBSA matrix) iii) by determining water sorption isotherms and kinetics and finally iv) by the study of the release in water of active or model migrants previously incorporated in the polar phase (sodium fluoresceinate, organic acids, glycine, diglycine). It has been observed that the diffusion phenomena in PLS / PBSA blends are controlled by the tortuosity generated by the presence of PBS and by the limited hydration of the polar phase at high PBSA contents in the blends for water sorption phenomena. Thus, the diffusion of fluorescein, for example, is much more influenced by the tortuosity (itself governed by the composition of the blends) than that of water, which is likely due to its higher molecular weight. For PEO / PBSA blends, distinct behaviors were observed according to the blends composition. For the blends with low or intermediate content of PBSA, rapid transport occurs mainly via the dissolution of the PEO. The morphology did not seem to influence the release kinetics. For high contents of PBSA, the release kinetics were dependent on the morphology and a time lag which is characteristic of permeation kinetics (release proportional to time) appeared. In conclusion, the multiphasic materials prepared by plastic processing look promising for the controlled release of polar migrants such as food preservatives to develop antimicrobial active packaging

In the present investigation, surface coatings employing laser surface alloying (LSA) and plasma electrolytic oxidation (PEO) processes have been prepared on Mg alloys. The coatings have been investigated for corrosion and wear behaviour. Two important Mg alloys based on Mg–Al system were selected namely, MRI 230D and AM50 as substrates. LSA coatings have been prepared employing Al and Al2O3 as precursors using different laser scan speeds. PEO coatings were prepared in standard silicate and phosphate based electrolytes employing unipolar, pulsed DC. Hybrid coatings using a combination of the two processes were also produced and investigated for corrosion and wear behaviour. Hybrid coatings of LSA followed by PEO (LSA+PEO) were investigated for effectiveness of sealing the cracks in the LSA coatings by subsequent PEO process and consequent improvement in the corrosion resistance. Hybrid coatings of PEO followed by LSA (PEO+LSA) were prepared with an objective of sealing the pores in the PEO coating LSA treatment. In an attempt to produce more compact PEO coatings, electrolyte containing montmorillonite clay additives was employed for the PEO process of AM50 Mg alloy. The coatings were produced employing different current densities and the effect of current density on the microstructure and corrosion behaviour of coating was investigated. Electrochemical corrosion tests of uncoated and coated alloys were carried out in 3.5 wt.% (0.6M)NaCl, neutral pH, solution with an exposed area of 0.5 cm2 for a time duration of 18.5 h. For the PEO coatings with clay additives, corrosion tests were conducted additionally in 0.5 wt.% (0.08 M) NaCl, neutral pH, solution for a time duration of 226.1 h. Wear behaviour of LSA coatings was analyzed by employing a pin on disc tribo–tester conforming to ASTM G–99 standard at ambient conditions with ground EN32 steel disc of hardness Rc 58 as the counterface. Tests were conducted under dry sliding conditions for a sliding distance of 1.0 km at a sliding velocity of 0.837 m/s employing normal loads of 10, 20, 30 and 40 N. Friction and wear behavior of PEO and PEO+LSA coatings were analyzed at ambient conditions by employing a ball−on−flat linearly oscillating tribometer conforming to ASTM G–133 standard. AISI 52100 steel ball of diameter 6 mm was employed as the friction partner. Wear tests were conducted under dry sliding conditions for a total sliding distance of 100 m at normal loads of 2 N and 5 N with oscillating amplitude of 10 mm and mean sliding speed of 5 mm/s. LSA coatings could not improve the corrosion resistance of MRI 230D Mg alloy. This was attributed to the presence of cracks in the LSA coating, which resulted in the accelerated galvanic corrosion of the substrate. LSA coatings improved the wear resistance at all loads. The improved wear resistance was attributed to β (Mg17Al12) phase and Al2O3 particles in the coating which increased the hardness of the LSA layer. No trend in corrosion and wear resistance with laser scan speed was observed for LSA coatings. PEO coatings improved the corrosion resistance of the MRI 230D Mg alloy significantly. The improved corrosion resistance was attributed to the enhanced barrier protection provided by dense barrier layer formed at the substrate/coating interface and to the insoluble phase constituents in the coatings. PEO coating was effective in improving the wear resistance at low loads/contact pressures. At higher loads, the coating underwent micro–fracture as a result of the porosity in the coatings. Hybrid coatings of LSA followed by PEO (LSA+PEO) in silicate based electrolyte improved the corrosion resistance of LSA coatings. However, the corrosion resistance was not improved to the extent of PEO coatings on as–cast alloy as a result of cracks in the primary coatings, which were not fully sealed by the plasma conversion products. No trend in corrosion resistance with laser scan speed was observed for LSA+PEOcoatings. In hybrid coatings of PEO followed by LSA (PEO+LSA), primary PEO coating was completely melted and mixed with applied precursor to form a single composite LSA layer. The corrosion resistance of the hybrid coatings was observed to be lower than that of the as–cast alloy. The presence of solidification cracks reduced the barrier properties and resulted in the accelerated galvanic corrosion of the substrate similar to LSA coatings. Hybrid (PEO+LSA) coatings exhibited improved wear resistance as compared to as–cast alloy at lower loads as a result of increase in the hardness due to β (Mg17Al12) phase and oxide/ceramic particles in the hybrid layer. At higher loads, hybrid coatings exhibited higher wear rate as compared to as–cast alloy and PEO coatings. This was attributed to three–body abrasive wear as a result of dislodged hard oxide/ceramic particles in the wear tracks. No trend in corrosion and wear resistance with laser scan speed was observed for PEO+LSA coatings. PEO coatings on AM50 Mg alloy by employing clay additives in the electrolyte resulted in the reactive uptake of clay particles producing a predominantly amorphous coating at low current density. Clay additives were effective in improving the compactness of the coating at lower current density. At higher current densities, the porosity of the coatings increased. The clay particles got re–constituted producing increasing amount of crystalline phases with increase in current density. Long term impedance measurements showed that clay addition as well as increased current density employed for the PEO process was not effective in improving the corrosion resistance of the coatings. At low current density, even though the coating with clay additives was more compact, it was deficient in MgO and consisted predominantly of an amorphous phase, which underwent fast dissolution in electrolyte thereby resulting in an early loss of barrier properties. At higher current densities, even though the coatings consisted of increased amount of MgO and crystalline phases, which resist dissolution in the electrolyte, the increased porosity and defective barrier layer resulted in easy permeation of the electrolyte into the substrate/coating interface, which resulted in much earlier loss of barrier properties and inferior corrosion resistance.

This work presents a basic research on the influence of electron beam technology modification on chemical, structural and phases changes of Elektron 21 magnesium alloy. The samples were systematically modified under various parameters of the electron beam and coatings on their respective surfaces were deposited via controlled plasma electrolytic oxidation (PEO) subsequently. The influence of the EB modification on the PEO coating formation was observed. Several samples with remelted fine-grained surface layer were obtained. Having a thickness of 10^1 to 10^3 µm, the average grain sizes in this layer were quantitatively evaluated. The performed EDS analysis revealed in identical chemical composition of the remelted surface layer and the original alloy material, despite the detected sample weight loss upon the EB treatment. XRD analysis revealed an increased content of Mg3(Nd,Gd) intermetallic phase in the remelted area. The PEO coatings were more compact and less porous as compared with their counterpart coatings on the original, unmodified alloy material.The results of the presented work showed, among others, a suitable microstructure and chemical composition of some of the modified samples that could potentially exhibit enhanced corrosion resistance as opposed to the unmodified material. The corrosion testing will be part of a follow-up study. More compact PEO coatings formed on some of the modified surface layers likely represent, too, a more durable variant as compared to the original material.

MSc (Med),Dept of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand / Pain is the net effect of multidimensional mechanisms that engage most parts of the central nervous system (CNS) and the treatment of pain is one of the key challenges in clinical medicine (Le Bars et al., 2001; Miranda et al., 2008). Polypharmacy is seen as a barrier to analgesic treatment compliance, signifying the necessity for the development of fixed dose combinations (FDCs), which allow the number of tablets administered to be reduced, with no associated loss in efficacy or increase in the prevalence of side effects (Torres Morera, 2004). FDCs of analgesic drugs with differing mechanisms of nociceptive modulation offer benefits including synergistic analgesic effects, where the individual agents act in a greater than additive manner, and a reduced occurrence of side-effects (Raffa, 2001; Camu, 2002). This study aimed at producing a novel, rate-modulated, fixed-dose analgesic formulation for the treatment of mild to moderate pain. The fixed-dose combination (FDC) rationale of paracetamol (PC), tramadol hydrochloride (TM) and diclofenac potassium (DC) takes advantage of previously reported analgesic synergy of PC and TM as well as extending the analgesic paradigm with the addition of the anti-inflammatory component, DC. The study involved the development of a triple-layered tablet delivery system with the desired release characteristics of approximately 60% of the PC and TM being made available within 2 hours to provide an initial pain relief effect and then sustained zero-order release of DC over a period of 24 hours to combat the on-going effects of any underlying inflammatory conditions. The triple-layered tablet delivery system would thus provide both rapid onset of pain relief as well as potentially address an underlying inflammatory cause. The design of a novel triple-layered tablet allowed for the desired release characteristics to be attained. During initial development work on the polymeric matrix it was discovered that only when combined with the optimized ratio of the release retarding polymer polyethylene oxide (PEO) in combination with electrolytic-crosslinking activity, provided by the biopolymer sodium alginate and zinc gluconate, could the 24 hour zero-order release of DC be attained. It was also necessary for this polymeric matrix to be bordered on both sides by the cellulosic polymers containing PC and TM. Thus the application of multi-layered tableting technology in the form of a triple-layered tablet were capable of attaining the rate-modulated release objectives set out in the study. The induced barriers provided by the three layers also served to physically separate TM and DC, reducing the likelihood of the bioavailability-diminishing interaction noted in United States Patent 6,558,701 and detected in the DSC analysis performed as part of this study. The designed system provided significant flexibility in modulation of release kinetics for drugs of varying solubility. The suitability of the designed triple-layered tablet delivery system was confirmed by a Design of Experiments (DoE) statistical evaluation, which revealed that Formulation F4 related closest to the desired more immediate release for PC and TM and the zero-order kinetics for DC. The results were confirmed by comparing Formulation F4 to typical release kinetic mechanisms described by Noyes-Whitney, Higuchi, Power Law, Pappas-Sahlin and Hopfenberg. Using f1 and f2 fit factors Formulation F4 compared favourably to each of the criteria defined for these kinetic models. The Ultra Performance Liquid Chromatographic (UPLC) assay method developed displayed superior resolution of the active pharmaceutical ingredient (API) combinations and the linearity plots produced indicated that the method was sufficiently sensitive to detect the concentrations of each API over the concentration ranges studied. The method was successfully validated and hence appropriate to simultaneously detect the three APIs as well as 4-aminophenol, the degradation product related to PC. Textural profile analysis in the form of swelling as well as matrix hardness analysis revealed that an increase in the penetration distance was associated with an increase in hydration time of the tablet and also an increase in gel layer thickness. The swelling complexities observed in the delivery system in terms of both the PEO, crosslinking sodium alginate and both cellulose polymers as well as the actuality of the three layers of the tablet swelling simultaneously suggests further intricacies involved in the release kinetics of the three drugs from this tablet configuration. Modified release dosage forms, such as the one developed in this study, have gained widespread importance in recent years and offer many advantages including flexible release kinetics and improved therapy and patient compliance.