O objetivo deste estudo foi investigar adesão, proliferação, atividade de fosfatase alcalina e de síntese de matriz mineralizada por células derivadas da granulação óssea (células GO-1) e fibroblastos gengivais humanos (FGH-1) em discos de titânio com diferentes tratamentos de superfícies. Discos de titânio comercialmente puro grau IV foram divididos em 4 grupos de acordo com o tratamento de superfície: (1) discos usinados L (controle); (2) discos usinados seguido de jateamento abrasivo (JATO); (3) discos usinados, jateados e tratados por subtração ácida (superfície NeoPoros NP); (4) discos com tratamento superficial para melhora da hidrofilia (superfície Acqua - ACQ). A microtopografia de superfície dos diferentes tipos de disco de titânio foi avaliada por meio de MEV. A composição química dos discos de titânio de superfícies L, JATO, NP e ACQ foi analisada por espectrometria de energia dispersiva de raios-X (EDS). Para determinar a influência dos diferentes tratamentos de superfície sobre a adesão de células de linhagens fibroblásticas gengivais e osteoblásticas, foram cultivadas células GO-1 e FGH-1 sobre os discos de titânio dos diferentes grupos e as células aderidas foram avaliados por meio de microscopia eletrônica de varredura (MEV) após 24h (adesão) e 48 h (proliferação). No ensaio de mineralização os discos de titânio foram corados com vermelho de alizarina para evidenciação dos nódulos de mineralização. Para avaliação da atividade de fosfatase alcalina, as células FGH-1 e GO-1 foram plaqueadas sobre discos de titânio, a atividade da FA foi observada nas células lisadas usando 25 &#x3BC;l da amostra em placa de 96 poços adicionado com 200 &#x3BC;L de fosfato p-nitrofenol (pNPP) e determinada em espectofotômetro. Não houve diferenças entre os grupos para os parâmetros de rugosidade encontrados nas amostras, com exceção do parâmetro Rsk(asimetria), onde diferenças significantes foram observadas do grupo L em relação aos grupos JATO, NP e ACQ (p< 0.05. Os implantes de superfície L e NP apresentaram apenas Ti, a superfície JATO apresentou, além do Titânio, as substâncias Oxigênio e Alumínio enquanto na superfície ACQ foram observados Titânio, Sódio e Potássio. No período de 24 horas após o cultivo celular, houve maior proliferação de células FGH sobre as superfícies L (89,43% ± 9,13;) e JATO (100%), neste período, observou-se que 100% das superfícies JATO e ACQ estavam recobertas por células GO. Apos 48h diferenças significantes entre o percentual de área recoberta por células FGH nas superfícies JATO comparativamente às superfícies NP e ACQ e, para as células GO, entre as superfícies NP comparativamente às superfícies JATO e ACQ. Houve maior percentual de área recoberta pelas células GO do que pelas células FGH. Houve formação de nódulos mineralizados em todas as superfícies, análise comparativa mostrou diferenças estatisticamente significantes para as células GO cultivadas em DMEM sobre as superficies L (31,45% ± 1,51%) e ACQ (54,94% ± 4,80%). A atividade de fosfatase alcalina foi maior em discos com superfície Lisa e hidrófilica(ACQ). Esses resultados sugerem que todas as superfícies favorecem a adesão e proliferação de fibroblastos gengivais e células osteoblásticas humanas. Superfícies moderadamente rugosas favorecem a maior adesão e proliferação de células osteoblásticas, assim como maior atividade de mineralização in vitro. / The objective of this study was to investigate adhesion, proliferation, alkaline phosphatase activity and matrix synthesis mineralized by cells derived from the bone granulation (GO cells) and human gingival fibroblasts (HGF) in titanium disks with different surface treatment. Titanium discs commercially pure grade IV were used, divided into 4 groups according to the surface treatment: (1) machined discs - L (control); (2) machined discs followed by abrasive blasting (JATO); (3) machined discs, sandblasted and treated by acid subtraction (Neoporos surface - NP); (4) disks with surface treatment to improve the hydrophilic (Acqua surface - ACQ). The surface microtopography of different types of titanium disk was evaluated by SEM. The chemical composition of the surfaces of titanium disks, L, JET, NP and ACQ was analyzed by energy dispersive X-ray spectrometry (EDS). To determine the influence of different surface treatments on the cell adhesion of gingival fibroblast and osteoblast lines were cultured GO-1 and FGH-1 cells on titanium discs of different groups and the adhered cells were assessed by electron microscopy (SEM) after 24 (adherence) and 48 h (proliferation). To test the mineralization titanium disks were stained with alizarin red for disclosure of mineralization nodules. To evaluate the alkaline phosphatase activity, the FGH-1 and GO-1 cells were plated on titanium disks, AP activity was observed in cells lysed using 25 &#x3BC;l of sample in a 96 well plate with 200 &#x3BC;l added phosphate p nitrophenol (pNPP) and determined in spectrophotometer. There were no differences between groups for the roughness parameters found in the samples, except for the parameter Rsk(asimetry) where significant differences were observed in the group L compared to JATO groups, NP and ACQ (p <0.05). The L and NP surface implants had only Ti, JATO surface showed, in addition to titanium, oxygen and the substances aluminum, while the ACQ surface were observed titanium, sodium and potassium. Within 24 hours after cell culturing, there was a greater proliferation of FGH on the cell surface L (89.43 ± 9.13%;) and JATO (100%), in this period, it was observed that 100% of the surfaces JATO and ACQ were covered by GO cells. After 48 hours there were significant differences between the percentage of area covered by FGH cells in JATO surfaces compared to NP surfaces and ACQ, and for GO cells, between NP surfaces compared with the JATO and ACQ surfaces. There was a higher percentage of area covered by GO cells than by FGH cells. There mineralized nodule formation on all surfaces, comparative analysis revealed statistically significant differences for the GO cells cultured in DMEM on the surfaces L (31.45% ± 1.51%) and ACQ (54.94% ± 4.80% ). Alkaline phosphatase activity was higher in discs with a smooth and hydrophilic surfaces (ACQ). These results suggest that all surfaces to promote adhesion and proliferation of gingival fibroblasts and human osteoblastic cells. Moderately rough surfaces leads to high adhesion and proliferation of osteoblast cells, as well as higher mineralization activity in vitro.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / A obesidade associada às alterações metabólicas, tais como a resitência à insulina, provoca significativas modificações no decorrer do processo de cicatrização. O objetivo desse estudo foi inicialmente avaliar os efeitos da resistência à insulina induzida por uma dieta com elevado teor de gordura durante o reparo tecidual. E, em seguida, investigar o papel dos macrófagos neste processo. Observamos que os animais submetidos à dieta hiperlipídica (RHL) tornaram-se intolerantes à glicose e resistentes à insulina, além de aumentarem as taxas plasmáticas de colesterol e triglicerídeos em relação aos animais alimentados com ração padrão (RP). O grupo RHL apresentou uma menor taxa de contração da lesão e reepitelização em relação ao grupo RP. Observamos ainda maior quantidade de células inflamatórias (células NOS 2-positivas, macrófagos, e neutrófilos), menor densidade de fibras do sistema colágeno e maior densidade de miofibroblastos e vasos sanguíneos no grupo RHL. O dano oxidativo estava maior no grupo RHL bem como a expressão proteica do fator de crescimento transformante-&#946;1 (TGF-&#946;1) e &#945;-actina de músculo liso (&#945;-SMA). O grupo RHL apresentou altos níveis plasmáticos de TNF-&#945; quando comparado com o grupo RP. Além disso, a proporção das células M1 (macrófagos ativados classicamente) e M2 (macrófagos ativados alternativamente) foi a mesma em ambos os grupos. Em relação a síntese e liberação de citocinas e fatores de crescimento avaliados através dos ensaios in vitro, observamos ainda que os níveis do fator de necrose tumoral-&#945; (TNF-&#945;) e interleucina-1&#946; (IL-1&#946;) estavam maiores no meio condicionado de macrófagos isolados dos animais do grupo RHL (MCRHL) em relacão ao meio condicionado de macrófagos isolados dos animais do grupo RP (MCRP). Além disso, os nossos resultados demonstraram claramente que os fatores solúveis produzidos por macrófagos isolados a partir de animais resistentes à insulina inibem a proliferação e a migração de fibroblastos. Através desses resultados podemos mostrar que a resistência à insulina retarda o processo de cicatrização e sugerir os macrófagos participam deste retardo. / Obesity associated with with metabolic alterations such as insulin resistance causes significant modifications during the healing process. Our aim was initially to analyse the effects of insulin resistance induced by a high- significant changes in skin combined fat diet during cutaneous wound healing. And then investigate the role of macrophages in this process. We observed that animals subjected to a high-fat diet (HFC) became glucose intolerant and insulin resistant and increased plasma cholesterol and triglycerides levels when compared to animals fed with a standard chow (SC). The HFC group had a lower rate of wound contraction and re-epithelialization than the SC group. Besides, HFC group presented a greater number of inflammatory cells (NOS 2- and F4/80-positive cells, and neutrophils), lower density of collagen fibers and higher density of myofibroblasts and blood vessels. Oxidative damage was greater in the HFC group as well as the protein expression of TGF-&#946;1 and &#945;-smooth muscle actin (&#945;- SMA). The HFC group presented higher levels of plasma TNF-&#945; when compared to RP group. Furthermore, the proportion of M1 cells (classically activated macrophages) and M2 (alternatively activated macrophages) was the same in both groups. Regarding to the synthesis and release of cytokines and growth factors evaluated by in vitro assays, we also observed that the levels of TNF-&#945; and IL-1&#946; were higher in conditioned medium of macrophages isolated from animals of HFC (MCHFC) group when compared to the conditioned medium of macrophages isolated from animals in of RP (MCSC) group. Furthermore, our results clearly demonstrate that soluble factors produced by macrophages isolated from insulin resistant animals inhibit the proliferation and migration of fibroblasts. Thus, we can show that insulin resistance delays wound healing process and suggest that the macrophages are involved in this delay.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Granulation is an industrial process where fine particles are bound together into larger granules. The process has numerous applications including the manufacture of pharmaceuticals and the production of cosmetics, chemicals, detergents and fertilisers. This thesis studies aspects of wet granulation which involves the application of a viscous binder, usually in the form of a spray, to an agitated bed of powder particles. Individual powder particles may adhere together, joined by small quantities of binder fluid called liquid bridges. By a process of collision and adherence additional particles may join the newly formed agglomerates. Agglomerates may also coalesce together which is a process that leads to granule formation. On the completion of this process, granules are typically dried.This thesis studies wet granulation on three different levels. First, micro-level investigations of liquid bridges between two and three particles are performed. For the two-particle case, the fluid profile of static (stationary) and dynamic (moving) liquid bridges is investigated. For the static case, a numerical solution to the Young-Laplace equation is obtained; this relates the volume of binder fluid to liquid bridge properties such as the inter-particle force. An analytic solution is also obtained, providing the liquid bridge profile in terms of known mathematical functions. For both solutions, the radii of the (spherical) primary particles may be different. The dynamic case is then studied using the Navier-Stokes equations with the low Reynolds number approximation. The motion of the approaching particles is shown to be damped by the viscosity of the liquid bridge. Static liquid bridges between three equally sized primary particles are then studied. Symmetry of the problem is used to obtain a numerical solution to the Young-Laplace equation. Liquid bridge properties are calculated in terms of the binder fluid volume. Experimental agreement is provided.Secondly, a model to estimate the stickiness (fractional wet surface area) of agglomerates is proposed. Primary particles are approximated as spheres and are added one at a time in a closely packed arrangement. The model includes parameters to control the inter-particle separation distance and the fluid saturation state. Computational geometry is used to obtain results which relate the number of particles and the volume of binder fluid to the stickiness of the agglomerates.Finally, a population balance model for wet granulation is developed by extending an earlier model to incorporate the effects of binder fluid. Functions for the inter-particle collision rate and drying rate are proposed, including functions which are derived from the geometric model, described above, for the case of maximum particle consolidation. The model is solved numerically for a range of coalescence kernels and results are presented which show the effect of binder volume and the drying rate.

La granulation sèche de poudres organiques pose des problèmes : parfois il faut une mise au point très longue avant d'obtenir les paramètres optimaux de compaction ; d'autres fois on n'y parvient pas. Bien connaître l'aptitude à la compaction et à la granulation des poudres reste ainsi un enjeu très important pour les industriels qui utilisent ou produisent des matériaux sous forme de poudre.<br />L'objet de cette étude est donc de chercher à mieux appréhender les liens qui peuvent exister entre les caractéristiques de la poudre, les paramètres d'alimentation et de compaction du procédé et les caractéristiques des plaquettes produites lors de la compaction en presse à rouleaux. Ainsi, par des expériences simples réalisées sur la poudre, le but est de gagner du temps sur l'optimisation du procédé ou de ne pas en perdre (si on trouve le moyen de savoir si oui ou non le produit peut être compacté). L'aspect "granulation" n'est pas traité ici dans son ensemble : l'étude s'arrête avant le passage de la plaquette dans le granulateur. Afin de répondre au mieux aux attentes de Rhodia, nous avons travaillé en parallèle sur deux fronts : d'une part au niveau expérimental, une presse à rouleaux instrumentée a été réalisée, pour permettre de visualiser un certain nombre de paramètres instrumentaux au cours de la compaction : le couple, l'entrefer et la distribution de pression à la surface des rouleaux ; d'autre part au niveau simulation numérique, en modélisant le procédé sur un logiciel du commerce. L'objectif est de comprendre grâce au montage expérimental les paramètres qui ont une réelle influence sur l'état des compacts produits, et à un niveau intermédiaire sur les profils de pression entre les rouleaux. Nous voulons aussi valider les résultats de la simulation numérique en les confrontant aux résultats expérimentaux ; le but ultime étant de pouvoir travailler de manière prédictive à partir des tests simples sur la poudre de départ, et d'essais de simulation. En résumé, l'objectif de ce travail de thèse peut s'énoncer comme suit : "A partir d'une poudre donnée, être capable par des expériences simples de caractérisation et grâce à la modélisation (numérique ou non) de : 1/prédire si cette poudre pourra être compactée en presse à rouleaux ; 2/connaître les paramètres optimaux de compaction ; 3/ savoir quelle qualité (homogénéité, densité, cohésion) pourra être obtenue au mieux sur les plaquettes produites ; et tout ceci en s'attachant à réduire au maximum le temps dévolu aux expériences et aux calculs numériques."

Tissue neovascularization in postnatal life occurs during post-traumatic tissue healing, neoplastic growth and in the endometrium during the reproductive cycle of females. Although embryonic angiogenesis has been intensively studied, far less is known about tissue revascularization and vessel remodeling in adults due to methodological difficulties. In the current studies, we developed a novel in vivo model of neovascularization that is performed on the chicken chorioallantoic membrane (CAM). A provisional matrix placed on the CAM was vascularized in response to FGF-2. In order to distinguish new from pre-existing vessels, the matrix was separated from the CAM by a nylon grid. Techniques to visualize the three dimensional structure of vascular networks and a method for rapid and semi-automated quantification were developed. This novel model allowed us to study the effects of potential inhibitors of tissue vascularization and their effects on the pre-existing vasculature. We found that while fumagillin or inhibition of MEK and Src inhibited only neovascularization, addition of cortisol or wortmannin was toxic to pre-existing vessels. The CAM model allowed intravital observations during extended periods of time, which together with immunohistochemical analysis revealed a novel mechanism of tissue vascularization. Tensional forces generated by myofibroblast-mediated contraction of the provisional matrix, induced and directed ingrowth of vascular tissue. During the initial stages of vascularization, the vascular network was recruited from the surrounding tissue through a non-angiogenic mechanism by elongation and enlargement of pre-existing vessels, which were moved as vascular loops with constant functional circulation. Ingrown vessels were remodeled, presumably through intussusception, fusion and pruning. The CAM model was validated by observations of neovascularization associated with healing of the injured mouse cornea.

There are mainly two manufacturing processes used in the pharmaceutical industry, namely direct compression and granulation of which granulation can be subdivided into wet granulation and dry granulation. Wet granulation is a process still widely used in the pharmaceutical industry and provides better control of drug content uniformity and compactibility at low drug concentrations. Lactose monohydrate and microcrystalline cellulose (MCC) were used as fillers in this study. Both these fillers possess unacceptable powder flow properties and the use of wet granulation may improve this property. One of the advantages of lactose monohydrate over MCC is that it is partially water soluble. A fractional factorial design was used in this study. Twelve tablet formulations were formulated containing different combinations of active ingredients (furosemide or pyridoxine hydrochloride), fillers (lactose monohydrate or MCC) and a binder (Kollidon® VA64) in three different concentrations (0.75, 1.5 or 3.0% w/w). The binder was used to produce granules by means of wet granulation, using ethanol as granulating fluid. The granules were dried in an oven and screened through different sized sieves to produce the final granulated powder formulations ready for tableting. A disintegrant (Ac-di-sol®) and lubricant (magnesium stearate) were incorporated into the granulated powder formulations extra-granular (0.5% w/w) and were kept as a constant in this study throughout all the formulations. A Turbula® mixer was used to mix the granulated powder formulations for a constant 5 minutes. During the first phase of the study, tablets were compressed using 2 compression settings (22 and 24). These compression settings were used to determine what effect different external pressures would have on the different tablet properties. Tablet weight for all the formulations was kept constant at 250 mg, although the volume of the matrix differed for each tablet formulation. The physical properties of the tablets were evaluated with regard to weight variation, mechanical strength (crushing strength and friability) and disintegration. Tablet formulation 12 yielded unsatisfactory tablets, due to poor powder flow into the die. Tablet formulations that contained the highest binder concentration (3.0% w/w) and were compressed at the highest compression setting (24) (formulations 4 and 9), exhibited the highest mechanical strength. The disintegration results revealed that the tablet formulations containing MCC as filler disintegrated faster compared to those containing lactose monohydrate. The increase in binder concentration caused an increase in mechanical strength, possibly decreasing tablet porosity, therefore prolonging disintegration time due to impeded water penetration into the tablet matrix. During the final phase of the study, dissolution studies were conducted on the different tablet formulations in 0.1 M HCl for 120 minutes. In terms of dissolution results, the initial dissolution rate (DRi) and extent of dissolution (AUC) were compared. It was found that the tablet formulations containing pyridoxine hydrochloride as active pharmaceutical ingredient (API) exhibited faster drug dissolution (higher DRi and AUC-values) compared to those tablet formulations containing furosemide. The faster dissolution exhibited by the pyridoxine hydro- chloride containing formulations can possibly be attributed to the fact that pyridoxine hydrochloride is good water soluble whereas furosemide is practically insoluble in water. The effect of the filler depended on the aqueous solubility of the filler and the concentration of the binder (Kollidon VA64) employed. An increase in binder concentration led to a decrease in the initial rate of dissolution as well as the extent of drug dissolution. In the case of the pyridoxine hydrochloride containing formulations, formulation 9 exhibited the slowest DRi and lowest extent of drug dissolution (1.40 ± 0.03 µg.cm-3.min-1 and 2396.52 ± 26.43 µg.cm-3.min respectively). In the case of the furosemide containing formulations, formulation 4 exhibited the slowest DRi and lowest extent of drug dissolution (0.22 ± 0.07 µg.cm-3.min-1 and 1018.62 ± 59.74 µg.cm-3 min respectively). In both cases, the formulations contained Kollidon VA64 in a concentration of 3% w/w and were compressed at compression setting 24. The disintegration process of tablets goes hand in hand with the dissolution process and results have shown that by establishing rapid contact between drug particles and the surrounding medium proves to be a necessity for rapid drug dissolution. Disintegration does not assure drug dissolution, but when prolonged, slower dissolution rates can be obtained, implying a slow rate and low extent of drug dissolution. The disintegrant in this study was incorporated extra-granular ensuring rapid tablet disintegration. However, due to binder concentration of 3% w/w, granule disintegration was probably negatively affected resulting in a lower drug surface area exposed to the surrounding dissolution medium, leading to a slower initial rate and extent of drug dissolution. From the results obtained during this study it was evident that formulation variables such as the type of filler, the concentration of the binder and compression setting employed during tablet manufacturing can have a ronounced effect on the pharmaceutical availability of the active ingredient. However, the extent of the effect was dependent on the aqueous solubility of the active ingredient. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

There are mainly two manufacturing processes used in the pharmaceutical industry, namely direct compression and granulation of which granulation can be subdivided into wet granulation and dry granulation. Wet granulation is a process still widely used in the pharmaceutical industry and provides better control of drug content uniformity and compactibility at low drug concentrations. Lactose monohydrate and microcrystalline cellulose (MCC) were used as fillers in this study. Both these fillers possess unacceptable powder flow properties and the use of wet granulation may improve this property. One of the advantages of lactose monohydrate over MCC is that it is partially water soluble. A fractional factorial design was used in this study. Twelve tablet formulations were formulated containing different combinations of active ingredients (furosemide or pyridoxine hydrochloride), fillers (lactose monohydrate or MCC) and a binder (Kollidon® VA64) in three different concentrations (0.75, 1.5 or 3.0% w/w). The binder was used to produce granules by means of wet granulation, using ethanol as granulating fluid. The granules were dried in an oven and screened through different sized sieves to produce the final granulated powder formulations ready for tableting. A disintegrant (Ac-di-sol®) and lubricant (magnesium stearate) were incorporated into the granulated powder formulations extra-granular (0.5% w/w) and were kept as a constant in this study throughout all the formulations. A Turbula® mixer was used to mix the granulated powder formulations for a constant 5 minutes. During the first phase of the study, tablets were compressed using 2 compression settings (22 and 24). These compression settings were used to determine what effect different external pressures would have on the different tablet properties. Tablet weight for all the formulations was kept constant at 250 mg, although the volume of the matrix differed for each tablet formulation. The physical properties of the tablets were evaluated with regard to weight variation, mechanical strength (crushing strength and friability) and disintegration. Tablet formulation 12 yielded unsatisfactory tablets, due to poor powder flow into the die. Tablet formulations that contained the highest binder concentration (3.0% w/w) and were compressed at the highest compression setting (24) (formulations 4 and 9), exhibited the highest mechanical strength. The disintegration results revealed that the tablet formulations containing MCC as filler disintegrated faster compared to those containing lactose monohydrate. The increase in binder concentration caused an increase in mechanical strength, possibly decreasing tablet porosity, therefore prolonging disintegration time due to impeded water penetration into the tablet matrix. During the final phase of the study, dissolution studies were conducted on the different tablet formulations in 0.1 M HCl for 120 minutes. In terms of dissolution results, the initial dissolution rate (DRi) and extent of dissolution (AUC) were compared. It was found that the tablet formulations containing pyridoxine hydrochloride as active pharmaceutical ingredient (API) exhibited faster drug dissolution (higher DRi and AUC-values) compared to those tablet formulations containing furosemide. The faster dissolution exhibited by the pyridoxine hydro- chloride containing formulations can possibly be attributed to the fact that pyridoxine hydrochloride is good water soluble whereas furosemide is practically insoluble in water. The effect of the filler depended on the aqueous solubility of the filler and the concentration of the binder (Kollidon VA64) employed. An increase in binder concentration led to a decrease in the initial rate of dissolution as well as the extent of drug dissolution. In the case of the pyridoxine hydrochloride containing formulations, formulation 9 exhibited the slowest DRi and lowest extent of drug dissolution (1.40 ± 0.03 µg.cm-3.min-1 and 2396.52 ± 26.43 µg.cm-3.min respectively). In the case of the furosemide containing formulations, formulation 4 exhibited the slowest DRi and lowest extent of drug dissolution (0.22 ± 0.07 µg.cm-3.min-1 and 1018.62 ± 59.74 µg.cm-3 min respectively). In both cases, the formulations contained Kollidon VA64 in a concentration of 3% w/w and were compressed at compression setting 24. The disintegration process of tablets goes hand in hand with the dissolution process and results have shown that by establishing rapid contact between drug particles and the surrounding medium proves to be a necessity for rapid drug dissolution. Disintegration does not assure drug dissolution, but when prolonged, slower dissolution rates can be obtained, implying a slow rate and low extent of drug dissolution. The disintegrant in this study was incorporated extra-granular ensuring rapid tablet disintegration. However, due to binder concentration of 3% w/w, granule disintegration was probably negatively affected resulting in a lower drug surface area exposed to the surrounding dissolution medium, leading to a slower initial rate and extent of drug dissolution. From the results obtained during this study it was evident that formulation variables such as the type of filler, the concentration of the binder and compression setting employed during tablet manufacturing can have a ronounced effect on the pharmaceutical availability of the active ingredient. However, the extent of the effect was dependent on the aqueous solubility of the active ingredient. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

Darbo tikslas – parengti augalinės žaliavos granuliavimo ir kapsuliavimo technologiją, atlikti biofarmacinius tyrimus ir panaudojus gautus rezultatus pagaminti eksperimentinę kapsuliuoto produkto seriją. Darbo uždaviniai: Įvertinti karčiojo kiečio augalinių miltelių technologines savybes; Parinkti ir pritaikyti tinkamą granuliavimo technologiją; Atlikti granulių kokybės vertinimą; Pritaikyti augalinės žaliavos kapsuliavimo technologiją; Atlikti kapsulių kokybės vertinimą ir biofarmacinius tyrimus, palyginti ir įvertinti laboratorijoje ir pusiau pramoniniu būdu pagamintų kapsulių kokybės rodiklius. Tyrimo objektas – karčiojo kiečio milteliai ir jų pagrindu pagaminti produktai. Metodai: atliktas karčiojo kiečio miltelių vertinimas, nustatant miltelių birumą, kūgio kampą ir suberiamąjį tankį. Drėgnos granuliacijos būdu pagamintoms granulėms nustatytas procentinis drėgmės kiekis, atliktas suberiamojo tankio nustatymas, išmatuotas granulių dydis. Įvertinta vidutinė kapsulių masė, nustatytas kapsulių suirimo laikas ir bendras fenolinių junginių kiekis išsiskiriantis iš vienos kapsulės. Rezultatai: karčiojo kiečio milteliai yra nebirūs, įsielektrinę, vidutinis dalelių dydis – 22,15 µm, jos nelygiais kraštais. Atlikus drėgną granuliaciją miltelių dalelės tapo lygesniais kraštais, vidutinis dydis – 16,67 µm. Daugeliu atveju suberiamasis tankis viršijo 0,3 g/cm3, išskyrus 2 proc. želatinos tirpalą ir 64 proc. cukraus sirupo tirpalą. Didžiausią kapsulės svorį pasiekėme su 5 proc... [toliau žr. visą tekstą] / Objective of work: to prepare plant material granulation and encapsulation technology to perform biopharmaceutical research and use the results to produce a series of experimental encapsulated product. Tasks: Evaluate wormwood plant powder technological features; Select and apply appropriate granulation technology; Perform pellet quality; Adapt plant material encapsulation technology; Perform quality assessment capsules and biopharmaceutical research, compare , and evaluate laboratory and semi- industrial scale capsules made of quality indicators. The object of investigation – wormwood powder and products based on this material. Method: wormwood powder biopharmaceutical evaluation set pourability, cone angle and tapped density. Wet granulation extruded pellets fixed percentage of moisture carried tapped density of measured grain size. The estimated average weight of capsules set time capsule disintegration and total phenolic compounds, different from one capsule. Results: wormwood powder is non – bulk, charged an average particle size – 22.15 μm, it’s rough edges. After a wet granulation powder particles become more even edges, the average size – 16.67 μm. In most cases, tapped density over 0.3 g/cm3, with the exception of 2 percent gelatin solution and 64 percent sugar syrup solution. The greatest weight of the capsule reached the 5 percent gelatine, 5 percent. methylcellulose and 64 percent granulate sugar syrup. The hardest part was filled in capsules granulate made with... [to full text]

This study was carried out to develop combined cultures which were composed of anaerobic and aerobic cultures, and could survive and operate under alternating aerobic and/or microaerobic / anaerobic conditions in semi-continuous and Upflow Sludge Blanket (USB) reactors. Granular combined cultures with median diameter of 1.28-1.86 mm and 0.8 mm were developed from suspended anaerobic and aerobic cultures in semi-continuous and USB reactors, respectively. Significant specific methanogenic activity (SMA, 14-42 mL CH4/g VSS.hr) and specific oxygen uptake rate (SOUR, 6-47 mg DO/g VSS.hr) values of combined granules in semi-continuous reactors were comparable to those of anaerobic and aerobic granules. Similarly, combined granules in USB reactors exhibited noteworthy SMA and SOUR values of 11-77 mL CH4/g VSS.hr and 10-75 mg DO/g VSS.hr, respectively. Combined granules developed in semi-continuous reactors were found to overcome the drawbacks of both anaerobic and aerobic granules such as the need for long start-up and low stability, respectively. Combined cultures were also developed from anaerobic granular and suspended aerobic cultures in three USB reactors aerated at 10 mL air/min for 4 hours/day (R2), every other day (R3) and 24 hours/day (R4). The use of combined cultures was found to be advantageous compared to the anaerobic granules for the treatment of low strength wastewaters. During municipal wastewater treatment at influent 5-day biochemical oxygen demand (BOD5) concentration of 53-118 mg/L (Hydraulic retention time, HRT: 0.75 day), combined cultures in R2, R3 and R4 exhibited average BOD5 removal efficiencies of 52, 75 and 76%, respectively. Combined granules developed in USB reactor also displayed significant BOD5 removal efficiencies (66-68%) during municipal wastewater application (HRT: 0.75 day). Combined cultures/granules developed in USB reactors might be proposed as an alternative for municipal wastewater treatment due to their advantages such as achievement of required discharge standards, prevention of biomass loss / settleability problems unlike activated sludge systems and possible methanogenic activity as well as high settling characteristics comparable to those of anaerobic granules.