A dissolução de um fármaco a partir de uma forma farmacêutica (FF) sólida oral é um pré-requisito para que o mesmo seja absorvido pelo organismo e cumpra seus efeitos terapêuticos. O ensaio de dissolução de medicamentos permite avaliar a quantidade de princípio ativo que é liberado a partir de sua FF, mimetizando in vitro o processo que ocorre no trato gastrointestinal (TGI). O DDDPlus® é o único programa de computador dedicado exclusivamente a simular ensaios de dissolução. O objetivo deste trabalho foi avaliar a capacidade do programa de computador DDDPlus® em fornecer perfis de dissolução in silico de comprimidos matriciais contendo metformina semelhantes aos perfis de dissolução in vitro e avaliar a possibilidade de substituir a comparação de perfis de dissolução in vitro de diferentes formulações de comprimidos matriciais contendo metformina pela comparação de perfis de dissolução in silico fornecidos pelo DDDPlus®.Para tanto, um planejamento estatístico foi realizado para obtenção de perfis de dissolução, variando a velocidade das pás e o uso do sinker. Os perfis de dissolução de 3 formulações teste (T1, T2 e T3) de comprimidos de liberação modificada por matriz polimérica contendo metformina foram comparadas pelos métodos de eficiência de dissolução (ED), tempo médio de dissolução (TMD), fator de diferença (f2) e fator de semelhança (f1). Os resultados indicaram o uso do sinker como fator determinante para a ED e TMD. Assim, o método que utilizava o sinker e a velocidade das pás de 50RPM foi utilizado para avaliar 4 produtos comercializados no Brasil. No DDDPlus® os ensaios de dissolução in vitro das formulações T1, T2 e T3 foram otimizadas para a obtenção das constantes de calibração (CC), as CC foram utilizadas para simular os ensaios de dissolução de T1, T2 e T3 em velocidades de 25 e 50RPM. Os perfis de dissolução simulados foram comparados aos perfis observados, resultando em valores de R2. Valores de R2 acima de 0,90 foram obtidos para todas as simulações realizadas utilizando CC de ensaios in vitro que utilizaram sinker, indicando o potencial do programa em auxiliar o desenvolvimento de novas formulações. Valores de R2 abaixo de 0,70 foram obtidos após a simulação de ensaios utilizando CC de ensaios in vitro que não utilizavam o sinker, indicando que o programa de computador não previu a adesão do comprimido ao fundo da cuba de dissolução durante o ensaio. Os perfis de dissolução simulados das formulações T1, T2 e T3 foram comparadas por f1 e f2 com os perfis de dissolução dos produtos do mercado. Tais comparações concluíram que o software não é indicado como substituto dos ensaios in vitro quando se almeja comparar perfis de dissolução. / Dissolution of a drug from an oral solid pharmaceutical form (FF) is a prerequisite for it to be absorbed by the body and to fulfill its therapeutic effects. in vitroDrug dissolution assay allows the amount of active principle released from a FF and mimics the in vivo the process that occurs in the gastrointestinal tract (TGI). DDDPlus® is the only computer program dedicated exclusively to simulating dissolution testing. The objective of this work was to evaluate the ability of DDDPlus® software to provide in silico dissolution profiles of matrix tablets containing metformin similar to in vitro dissolution profiles and to evaluate the possibility of replacing in vitro dissolution profiles comparison of different formulations of matrix tablets containing metformin for a comparison of in silico dissolution profiles provided by DDDPlus®. For this purpose, a statistical design was used, varying agitation speed and the use of sinker to obtain dissolution profiles for 3 test formulations (T1, T2 and T3) of polymer matrix-modified release tablets containing metformin. Dissolution profiles were compared by means of dissolution efficiency (ED), mean dissolution time (TMD), difference factor (f2) and similarity factor (f1). The results indicated the use of sinker as a determinant factor for ED and TMD. Thus, the method that used sinker and agitation speed of 50RPM was used to evaluate 4 products commercialized in Brazil. in vitro dissolution tests of the T1, T2 and T3 formulations were optimized using In DDDPlus® to obtain the calibration constants (CC), which were used to simulate dissolution profiles of T1, T2 and T3 at speeds of 25 and 50RPM. in silico dissolution profiles were compared to in vitro dissolution profiles, resulting in R2 values. R2 values above 0.90 were obtained for all simulations performed using CC from in vitro assays using sinker, indicating the potential of the program to assist the development of new formulations. R2 values below 0.70 were obtained after the simulation of assays using CC from in vitro assays that did not use the sinker, indicating that the computer program did not predict adhesion of the tablet to the bottom of the dissolution cell during the assay. The simulated dissolution profiles of the T1, T2 and T3 formulations were compared by f1 and f2 with the dissolution profiles of the market products. Such comparisons concluded that the software is not indicated as a substitute for in vitro assays when comparing dissolution profiles is desired.

Este trabalho teve por finalidade desenvolver um método para a caracterização do perfil de dissolução de suspensões de mebendazol (MBZ), discriminatório para as formas polimórficas do fármaco. Pertencendo a classe II do Sistema de Classificação Biofarmacêutica (SCB), além da baixa solubilidade, o MBZ é bastante crítico por apresentar-se comercialmente disponível em duas formas polimórficas (A e C) e misturas destas. Além disso, pouca informação é encontrada acerca de métodos de dissolução de suspensões. O material apresentado está dividido em três capítulos, sendo o primeiro deles uma revisão da literatura sobre a dissolução de suspensões de fármacos que apresentam polimorfismo. Neste capítulo é feita uma abordagem sobre questões relacionadas ao desenvolvimento de métodos, como inserção das amostras na cuba de dissolução, agitação, uso de tensoativos no meio e a quantificação do fármaco. No segundo capítulo é apresentado o desenvolvimento do método de dissolução, com ênfase no estudo da solubilidade das formas polimórficas A e C de MBZ e sua interação com tensoativos. Foram realizados ensaios de solubilidade pelo método do equilíbrio, cálculo de concentração micelar crítica para os tensoativos lauril sulfato de sódio e polissorbato 80, sendo ao final realizado delineamento experimental (DOE) para o desenvolvimento do método. Pela avaliação do DOE, o local de inserção da amostra não influencia a dissolução de MBZ, por outro lado, a presença de tensoativo, assim como a forma polimórfica empregada, exercem efeito nos resultados apresentados. A partir destas informações, o método indicado para avaliação das suspensões de MBZ com potencial discriminatório de suas formas polimórficas foi definido pela utilização do aparato 2 (pá) a 75 rpm, com 2 litros de HCl 0,1 M sem tensoativo, como meio de dissolução. No último capítulo, o método desenvolvido foi utilizado na avaliação de especialidades farmacêuticas adquiridas no Brasil e em alguns países da América Latina, sendo os respectivos perfis de dissolução, comparados por meio de uma análise multivariada de componentes principais, com formulações contendo o MBZ em diferentes proporções de polimorfos. A partir dos resultados, foi possível observar que grande parte das formulações comercializadas não apresentaram perfil de dissolução satisfatório, isso pode estar relacionado com a presença considerável de polimorfo A nas matérias-primas utilizadas, comprometendo assim a sua solubilidade. / The aim of this work was to develop a method for characterization of the dissolution profile of mebendazole (MBZ) suspensions, being discriminatory for the polymorphic forms of the drug. MBZ belongs to class II of the Biopharmaceutics Classification System (BCS), besides its low solubility, it is very critic, being commercially available in two polymorphic forms (A and C) and their mixtures. Moreover, there is low information about dissolution methods for suspensions. The text presented herein is divided into three chapters, the first chapter is a literature review about dissolution of suspensions containing drugs that present polymorphism. In this chapter is made a discussion about the variables of the method, as sample insertion in the dissolution vessel, rotation speed, use of surfactants in the dissolution medium and drug quantification. The development of the dissolution method, focused on the solubility study of MBZ polymorphic forms A and C and their interaction with surfactants is presented in the chapter 2. Some tests were performed: solubility using shake flask method, calculation of micellar critical concentration for the surfactants sodium lauryl sulphate and polysorbate 80, and an experimental design (DOE) was done for developing the method. By DOE evaluation, the sample insertion site does not influence on MBZ dissolution, but the presence of surfactant and the polymorphic form used, show effect on the results. Based on these information, the method indicated for evaluation of MBZ suspensions, with discriminatory power for its polymorphic forms was defined by using apparatus 2 (paddle) at 75 rpm and 2 L of 0.1M HCl without surfactant as dissolution medium. In chapter 3, the method developed was used to evaluate pharmaceutical suspensions from Brazil and from some countries of Latin America. The respective dissolution profiles were compared by means of multivariate analysis of principal components with formulations containing MBZ in different polymorphs ratios. From the results, it was possible to observe that a great part of the commercially available formulations do not presented a satisfactory dissolution profile, and this fact can be related to a considerable amount of the crystalline form A in the raw material, which compromises its solubility.

O presente trabalho teve como objetivo desenvolver metodologia para avaliação da dissolução intrínseca (DI) de amostras de albendazol (ABZ) e mebendazol (MBZ), empregando-se o método de disco rotativo. Inicialmente foi realizada a caracterização físico-química dos fármacos, empregando-se os ensaios de termogravimetria (TG), calorimetria exploratória diferencial (DSC), difratometria de raios X (DRX), microscopia eletrônica de varredura (MEV), densidade verdadeira, área superficial e tamanho de partícula, para sete amostras de ABZ e oito de MBZ. Com as análises de DRX e DSC foi possível verificar a presença dos polimorfos I e II, além de outras estruturas cristalinas nas amostras de ABZ. Em relação ao MBZ foi possível identificar os polimorfos A, C e a mistura destes polimorfos. Mediante o ensaio de solubilidade, verificou-se que as amostras que possuem o polimorfo C foram as mais solúveis nos meios de HCl 0,1N e suco gástrico. Finalmente, desenvolveu-se a metodologia para a avaliação da DI de ABZ e MBZ. Para avaliar o impacto das condições de ensaio na DI, escolheu-se uma amostra de ambos fármacos, que foi submetida a diferentes ensaios conforme delineamento experimental ortogonal de Taguchi do tipo L9(34). Verificou-se que tanto para o ABZ quanto para o MBZ, a variável que apresentou maior impacto na velocidade de dissolução intrínseca (VDI) foi o meio de dissolução. Dessa maneira, selecionaram-se as condições para a realização dos ensaios comparativos entre as amostras (diferentes fornecedores). Observou-se que as amostras que apresentam o polimorfo II (ABZ) e o C (MBZ) são aquelas que mostraram maiores valores de VDI. As condições empregadas para o estudo da VDI das amostras dos fármacos permitiram evidenciar diferenças entre os polimorfos demonstrando que a técnica de dissolução intrínseca é viável na caracterização das formas polimórficas de ABZ e MBZ. / The purpose of this study was to develop a methodology for evaluating the intrinsic dissolution (ID) of samples of albendazole (ABZ) and mebendazole (MBZ), employing the rotating disk method. Initially, a physicochemical characterization of seven samples of ABZ and eight samples of MBZ was carried out through thermogravimetric tests (TG), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM), as well as evaluations of true density, surface area and particle size. With the XRD and DSC analyses, it was possible to ascertain the presence of polymorphs I and II, as well as other crystalline structures in the ABZ samples. With regards to MBZ, it was possible to identify polymorphs A and C, as well as a mixture of these polymorphs. With the execution of a solubility test, it was ascertained that the samples with polymorph C were the most soluble in the HCl 0.1N and gastric acid media. Finally, a methodology for the evaluation of the ID of ABZ and MBZ was developed. In order to evaluate the impact of the test conditions on ID, samples of both drugs were chosen, which were then subjected to different tests, according to the L9 (34) Taguchi experimental orthogonal array. It was ascertained that for both ABZ and MBZ, the variable with the greatest impact on the intrinsic dissolution rate (IDR) was the dissolution medium. Accordingly, the conditions for the execution of comparative tests between the samples were selected (different suppliers). It was observed that the samples that presented the polymorph II (ABZ) and C (MBZ) were also those that presented the greatest IDR values. The conditions employed for the IDR study of the drug samples enabled differences between the polymorphs to be ascertained, thus demonstrating that the intrinsic dissolution technique is viable for the characterization of polymorphic forms of ABZ and MBZ.

A dissolução do carbonato está ligada à circulação dos oceanos e às variações climáticas. Através desse estudo foi possível identificar, durante o último ciclo glacial (150 mil anos), três eventos de dissolução na Bacia de Santos, durantes os estágios isotópicos marinhos 5d, 5b e 4. Para isso foram utilizados indicadores de dissolução micropaleontológicos, geoquímicos e sedimentares. Através destes indicadores foi possível inferir quais processos estão associados à dissolução do carbonato durante estes períodos. Os indicadores micropaleontológicos densidade área (ρA), espécies resistentes à dissolução (ERD e BDI) e índice de fragmentação (IF) foram capazes de identificar o início dos eventos de dissolução, enquanto os indicadores de variação tamanho de grão no sedimento bruto, teor de carbonato de cálcio (%CaCO3) em diferentes frações de tamanho, razão entre foraminíferos bentônicos e planctônicos (B/P) e peso normalizado (SBW) foram relacionados ao auge da dissolução. Os indicadores com base em cocolitoforídeos (CEX\'), índice Broecker/Clark e índice Chiu/Broecker apresentaram resultados inconclusivos. Observou-se que durante os três eventos de dissolução houve um aumento na contribuição de uma massa d\'água de origem sul (mais corrosiva ao carbonato) na região, indicado a partir da variação de δ13Cbentônico. Os eventos de dissolução também coincidiram com o aumento do aporte de sedimento não-carbonático (indicador de aporte continental, Fe/Ti e Ti/Ca). Os indicadores de paleoprodutividade (PP, RN e razão G. bulloides/G. ruber) não indicaram um aumento de produtividade primária durante os eventos de dissolução, de modo que a produtividade não foi considerada como um dos processos principais que induziram os eventos de dissolução neste estudo. As profundidades em que estes testemunhos se encontram (∼2000 m) também eliminam a possibilidade de que a dissolução tenha ocorrido em função da variação da posição da lisoclina, mesmo considerando que esta tenha estado ∼1000 m mais rasa durante o último período glacial. Desta forma, acreditamos que os eventos de dissolução estejam relacionados com a maior contribuição de uma massa d\'água de sul, mais corrosiva ao carbonato, em torno de 2000 m de profundidade, durante os MIS 5d, 5b e 4, como resultado da reorganização das massas d\'água profundas na região (uma redução na intensidade da AMOC) nestes períodos. / The calcium carbonate dissolution is linked to ocean circulation and climate change. Through this study it was possible to identify, during last glacial cycle (150 kyrs), three dissolution events occurring in the Santos Basin, during MIS 5d, 5b and 4. For this, micropaleontological, geochemical and sedimentary proxies were used. Through these proxies it was possible to infer which processes are associated with the carbonate dissolution during this period. The micropaleontological proxies of area density (ρA), dissolution resistent species (ERD and BDI) and fragmentation index (IF), were able to identify the beginning of the dissolution events, while the proxies of grain size variation, calcium carbonate content in different size fractions, benthic/planktonic ratio (B/P) and size normalized weight (SBW) were related with the dissolution peak. The proxies based in cocoliths (CEX\'), Broecker/Clark Index and Chiu/Broecker Index presented inconclusive results. It was observed that during the three dissolution events there was an increase in the contribution of the water mass of southern origin (more corrosive to the carbonate) in the region, indicated from the variation of δ13C in benthic foraminifera. This increase also coincided with the increase in the contribution of non-carbonate sediment (continental input indicator -IAC, Fe/Ca and Ti/Ca). The paleoproductivity proxies (based in cocoliths - PP, RN, and G. bulloides/G. ruber ratio) did not indicate an increase in primary productivity during dissolution events, therefore productivity was not considered as one of the processes that led to dissolution in this study. The depths at which these sediment cores are found (∼2000 m) also eliminate the possibility that the dissolution occurred as a function of the variation of the position of the lysocline, even if considering that it was ∼1000 m shallower during the last glacial period. In this way, we believe that the dissolution events are related to an increased southern-sourced water mass more corrosive to the carbonate during MIS 5d, 5b and 4, which implies the reorganization of the water masses in the region and a reduction in the strength of AMOC during these periods.

The objective of this study is to investigate cocrystal solubility and dissolution behavior to elucidate the factors affecting these processes in various media. Six cocrystals with xanthines (theophylline (THP), caffeine (CAF) and theobromine (THB)) were prepared and characterized by powder X-ray diffraction and thermal methods. Two cocrystals (CAFCA I and THBSA) are new solids and their crystal structures were determined by single crystal X-ray diffraction. Cocrystal solubility behavior depended on the dissolving complex solubility and its dissociation behavior in solution. Two THP cocrystals - one with acetaminophen (ACE) and one with citric acid (CA) created different degrees of free THP supersaturation in solubility and dissolution studies. High transient THP supersaturation caused almost immediate THP hydrate crystallization from THPCAH and led to non-congruent solubility behavior. Such behavior was not observed with the ACETHP because free THP supersaturation was not sufficient to induce rapid crystallization but did so over longer equilibration times. Three salicylic acid (SA) cocrystals with xanthines (THP, CAF, and THB) were prepared; two (THPSA and CAFSA) had low aqueous solubility compared to their pure components and one (THBSA) had higher solubility. Both cocrystal components in these cocrystals produced higher solubility/dissolution rates in alkaline media due to ionization. Also, at higher pH, THB precipitated from THBSA solutions because of higher THB supersaturation under alkaline conditions. Caffeine (CAF) and theophylline (THP) both form cocrystals with citric acid (CA) which is a highly water-soluble cocrystal former. Both CAFCA Form I and II solubility and dissolution behavior were studied. THPCAH exhibited non-congruent dissolution because of rapid precipitation of THP hydrate on the dissolving cocrystal surface. CAFCA exhibited congruent dissolution because it did not produce sufficient supersaturation to precipitate CAF hydrate during dissolution. CA cocrystals also have the unusual behavior of high viscosities produced in the dissolution boundary layer due to CA’s high solubility. These viscosities alter diffusion coefficients which reduce dissolution rates from that expected based purely on solubility. To further understand cocrystal dissolution, a diffusion-convection-reaction (DCR) model was developed to predict cocrystal dissolution rates in various media. This model predicted concentration profiles of all species (complex, free components and reactive species) in the diffusion layer of a rotating disk intrinsic dissolution system. Predicted dissolution rates had varying degrees of agreement with experimental data depending on the cocrystal model and the medium into which the cocrystal dissolved.

The dissolution behavior of a drug substance is an important part of its bioavailability. Three solid dissolution mechanisms are recognized: transport control, interface control and mixed-kinetic control. The mixed-kinetic control mechanism is not well studied as the majority of dissolution phenomena in pharmaceutical research are assumed to be transport-controlled. A phenomenological model for mixed-kinetic control was developed in which the interfacial step comprises molecular detachment and re-deposition and is described by chemical kinetic theory. This model encompasses interface control and transport control as limiting cases. Experimental studies on three organic compounds showed that they dissolved by transport control at 37°C, but exhibited certain degrees of interface control at lower temperatures (10°C and 3°C), which, according to the model, indicates that reducing the dissolution temperature slowed down re-deposition more than transport. Using mathematical approaches derived from the model, up to 27% interface control was calculated from the experimental results. The second experimental investigation showed significant degrees of interface control in benzoic acid dissolution in sodium dodecyl sulfate (NaDS) solutions at 25°C. The dissolution behavior was well described by the mixed-kinetic control model and up to 73% interface control was calculated. An extension of the model was proposed to describe a potential micelle-interface interaction mechanism indicated by the model-fitted parameters. The third investigation showed that FD&C Blue #1, a water-soluble dye, inhibited sulfathiazole dissolution in acidic media but not in water. The inhibition was attributed to the blocking of dissolution sites by dye adsorption. A potential pH-dependent adsorption mechanism was proposed in which protonation at sulfathiazole solid surface gives rise to preferential dye adsorption on detachment rates and thus reduced dissolution rates.

Iron-based alloys containing 15% chromium, 2-3% molybdenum and 0.02-1.7% carbon, consisting of M23C6 and M6C carbides in an austenitic matrix were oxidised at 8500C to study their oxidation resistance and a precipitate-free zone formation. Alloy design was carried out using a thermodynamic software Thermo-Calc. Carbides in these alloys were expected to dissolve during oxidation, releasing chromium required for the protective oxide formation. Decarburisation of the matrix was expected to trigger the carbide dissolution, and form a precipitate-free zone. Transformation of the austenitic into ferritic matrix in the precipitate-free zone was expected be essential for providing a fast chromium supply to the oxide/alloy interface. Upon exposure to pure oxygen, most of the alloys oxidised non-protectively due to the fast oxidation attack and low chromium content in the matrix, while carbide dissolution was too slow. The alloys were then pre-oxidised in H2+10%H2O to grow a purely chromia scale. In this low oxygen partial pressure environment, carbides in the alloy's sub-surface dissolved and formed a ferritic precipitate-free zone. The precipitate dissolution model developed by previous investigators was then tested and proven to be valid in this iron-based alloy system. The endurance of the pre-formed chromia scale with its underlying precipitate-free zone was then tested in pure oxygen environment. All of the alloys that had successfully developed a ferritic precipitate-free zone in the pre-oxidation stage, survived the subsequent oxidation in pure oxygen up until 3 weeks observation. Although x-ray diffraction found some minor iron oxides, the oxide consisted of mainly Cr2O3. Since iron activity had increased and iron oxides had become stable after the pure oxygen gas was introduced, the growth of the precipitate-free zone had to compete with the rate at which it was consumed by oxidation. It was concluded that the transformation from austenite to ferrite at the subsurface region of the alloy could be achieved provided that the volume fraction of the carbides did not exceed 0.2. Evidence indicated that the chromia scale grew by chromium provided by the dissolving carbides. Pre-oxidation led to a promising use of the alloys at atmospheric oxygen pressure.

Nous présentons dans cette thèse deux approches de modélisation 3D de la gravure chimique des monocristaux. A partir de la géométrie initiale d'un cristal et de ses propriétés physiques, les modèles décrits permettent de prévoir l'évolution de la forme du cristal au cours du temps. La prémière méthode que nous proposons est une extension en 3D de la construction géométrique dûe à Wulff et Jaccodine, basée sur l'analyse de résultats expérimentaux. Nous montrons qu'un sommet 3D peut être représenté par une composition de demi-espaces, dont chacun se déplace suivant une vitesse correspondant à son orientation. Nous étudions ensuite les limitations de cette méthode, liées à son implémentation. La seconde méthode que nous proposons s'appuie sur un modèle théorique original. Nous établissons tout d'abord une propriété applicable aux surfaces de classe C1 sur lesquelles la vitesse d'un point ne dépend que de la normale en ce point. Nous montrons ensuite qu'il est possible d'approcher la forme d'un cristal polyédrique par une surface de classe C1 et ainsi de lui appliquer le résultat précédent par passage à la limite. Pour représenter la forme du cristal et la trajectoire des points de sa surface, nous utilisons la notion d'espaces fibres. Nous présentons enfin une implémentation sous forme d'acteurs de cette méthode en 2D et montrons comment la méthode peut être étendue en 3D.

La cellulose, polymère naturel appartenant à la famille des polysaccharides, est non fusible. Pour la mettre en forme, il est donc nécessaire soit de la dériver, soit de la solubiliser. L'objectif de notre travail est de préciser les mécanismes qui conduisent à la dissolution de la cellulose native. Cinq mécanismes sont observés lors de cette étude, basée sur des fibres de cellulose native d'origine diverse (coton, bois, ramie, jute, lin, chanvre, sisal et abaca). Chaque échantillon est observé dans une large gamme de systèmes aqueux (NMMO - eau à différentes teneurs en eau ou hydroxyde de sodium - eau - additif) et des liquides ioniques. Des données recueillies sur des échantillons dépourvus de leurs parois externes suite à un traitement enzymatique, ainsi que des dérivés cellulosiques, viennent compléter cette étude. Nous avons identifié cinq mécanismes de gonflement et de dissolution de fibres de cellulose native : Mode 1: dissolution rapide par désintégration de la fibre en fragments Mode 2: gonflement par ballonnement, dissolution de toute la fibre Mode 3: gonflement par ballonnement, dissolution partielle de la fibre Mode 4: gonflement homogène, non dissolution de la fibre Mode 5: pas de gonflement ni de dissolution (cas d'un système non solvant) Malgré les différences morphologiques entre toutes les fibres de cellulose testées et les dérivés cellulosiques, les mécanismes de gonflement et de dissolution restent similaires. Trois zones le long des fibres de cellulose sont définis lors d'un mécanisme impliquant un gonflement par ballonnement: les ballons, la membrane des ballons, les sections non gonflées (zones situées entre les ballons). Chacune de ces zones présentent un mécanisme de dissolution particulier. Le mode 2 est donc détaillé en 4 étapes. Les ballons sont des entités constituées d'une membrane (paroi primaire, plus une partie de la paroi secondaire), caractérisée par une structure hélicoïdale. La membrane est la partie de la fibre la plus difficile à dissoudre. Il est important de noter que la cellulose à l'intérieur des ballons est dissoute. Les mécanismes de gonflement et de dissolution ne sont pas liés à la nature chimique des agents solvants. La qualité du solvant influe évidemment sur le mode de dissolution induit, mais le facteur clé des mécanismes est la structure morphologique de la fibre.

La cellulose, bio-polymère de la famille des polysaccharides, fait depuis des années l'objet de nombreuses études de recherches visant une meilleure maîtrise de sa modification et de sa mise en forme. N'étant pas fusible en dessous de sa température de dégradation, la cellulose nécessite une mise en forme par dissolution. Pourtant, les procédés utilisés aujourd'hui pour sa mise en forme ne sont pas toujours bien optimisés entraînant une perte de matière ou des qualités du produit final qui ne sont pas toujours celles visées par l'industrie. Cette limitation est en partie due à sa structure complexe qui rend les chaînes de la cellulose difficilement accessibles. L'objectif scientifique de notre travail était d'analyser et essayer de comprendre certains des paramètres qui peuvent avoir une influence sur l'accessibilité de la cellulose: état humide, application d'une tension mécanique uniaxiale, irradiation. Nous avons montré que la structure poreuse de la cellulose est un facteur important à prendre en compte dans son accessibilité. Ainsi, en présence d'un mauvais solvant comme le NaOHeau les fibres de cellulose montrent une meilleure accessibilité dans l'état jamais séché en comparaison avec les fibres à l'état séché, en raison d'une structure plus ouverte des fibres. La porosité a également été mise en évidence lors du séchage et re-humidification des surfaces modèles où nous avons mis en évidence le rôle des microporosités dans la reprise en eau. Ceci nous a permis de déduire que la faible hornification observée sur les produits régénérés à partir du procédé viscose est due à l'existence de microporosités à la surface de macroporosités qui ne permettent pas le contact entre les parois des pores lors de leur fermeture pendant le séchage, limitant fortement la capacité à créer des liaisons hydrogène irréversibles. Nous avons également montré qu'un facteur à prendre en compte lorsque l'on veut effectuer une modification chimique de la cellulose est le besoin que les chaînes soient suffisamment mobiles pour accéder à un éventail de conformations spécifiques.