Magister Pharmaceuticae - MPharm / Artemisia afra (A. afra) is traditionally used for a variety of ailments and contain flavonoids e.g. luteolin which may contribute to some of its activity. It is generally administered as a tea or decoction, and such liquid dosage forms present challenges as far as long term storage and stability are concerned, as well as sub-optimal oral bioavailability of actives they contain. Freeze dried aqueous extracts (FDAE) can alleviate such problems but may be hygroscopic and unstable. The use of modified forms of FDAE can counter the problem of hygroscopicity (e.g. use of alginate) and alleviate the issue of sub-optimal bioavailability of plant actives (e.g. polymethylmethacrylate). The objectives of this study, were to: (1) prepare the freeze dried aqueous extract (FDAE) and modified forms, which include alginate-extract beads (alginate-FDAE) and polymethylmethacrylate coated alginate matrix beads of herbal extract (PMMA-alginate-FDAE) of the FDAE of A. afra, (2) determine and compare the pharmaceutical characteristics of the above mentioned preparations of A. afra,(3) quantify and compare the total flavonoid and specifically luteolin levels of the different forms of A. afra,(4) evaluate and compare the release characteristics of FDAE of A. afra from the alginate-FDAE and PMMA-alginate-FDAE beads in gastrointestinal fluids and (5) determine the intestinal permeability of luteolin contained in selected modified Artemisia afra extract preparations. It was hypothesized that making the alginate beads and the polymethylmethacrylate coated alginate beads would make the FDAE less hygroscopic with a lower moisture content, that the rate of release of luteolin from A. afra FDAE into gastrointestinal fluids would be faster than from the modified forms, and that the effective gastrointestinal permeability of luteolin in the alginate-FDAE and PMMA-alginate-FDAE beads of A. afra is equal to that in FDAE. To realize these objectives, the FDAE was prepared by freeze drying the aqueous extract of the A. afra dried leaves, alginate-FDAE prepared by dispersing FDAE into 4% sodium alginate solution, then adding the resulting stock solution into a 2% calcium chloride solution and drying resulting beads and PMMA-alginate-FDAE prepared by a modified water-in-oil-in-water emulsion solvent evaporation method using water as an internal aqueous phase. Using pharmacopoeial methods and methods adapted from other workers the organoleptic and pharmaceutical characteristics were determined to compare the pharmaceutical quality of these preparations of A. afra. To identify and determine the levels of luteolin in the plant preparations, a validated HPLC assay was developed. Finally, the in situ perfused rat intestine model was used to determine the in vitro bioavailability, i.e. gastrointestinal permeability, of luteolin from solutions containing luteolin in pure form, FDAE, alginate-FDAE and PMMA-alginate-FDAE. The A. afra forms were obtained in moderate to good yields and FDAE was brown and hygroscopic in nature, the alginate beads dark brown free flowing and spherical in shape and the PMMA-alginate beads light brown in colour with rough edges. The A. afra plant forms on average contained 0.185 ± 0.24, 0.067 ± 0.014, 0.012 ± 0.071 μg/mg of free luteolin (n=3) in FDAE, alginate-FDAE and PMMA-alginate-FDAE respectively and 0.235 ± 0.026, 0.079 ± 0.093, 0.058 ± 0.082 μg/mg of total luteolin (n=3) in FDAE, alginate-FDAE and PMMAalginate- FDAE respectively. The Plumen values for intestinal uptake of luteolin were significantly higher from solutions of A. afra forms than the pure luteolin solution (i.e. Plumen values in the range of 0.02 - 0.035 cm/s for all plant forms vs Plumen values in the range of 0.010 - 0.014 cm/s for pure luteolin, t-test p = 0.0252). The permeability of luteolin in FDAE appeared to be slighter greater than that of the modified forms (Plumen values >0.03 cm/s for FDAE and Plumen values <0.03 cm/s for both modified forms). In summary, the results showed that, the modified A. afra forms; alginate-FDAE and PMMAalginate- FDAE were of acceptable pharmaceutical quality with luteolin better taken up in the plant forms than in its pure form. The A. afra forms prepared had similar rates of uptake (permeability) of free and total luteolin with the rates being highest for the FDAE. Collectively, these results indicate that alginate-FDAE and PMMA-alginate-FDAE bead forms should be suitable for use in a solid dosage form (e.g. tablet or capsule) of A. afra.

Thesis. 1976. M.S.--Massachusetts Institute of Technology. Dept. of Nutrition and Food Science. / Microfiche copy available in Archives and Science. / Bibliography: leaves 121-127. / M.S.

No description available.

No description available.

Every year, accidents, falls, sport injuries and other incidents cause thousands of people to suffer spinal cord injury (SCI). In the United States alone, it is estimated that the number of Americans that live with SCI is around 259,000, with 12,000 new cases that happen annually (1). These injuries lead to spinal cord damages expressed by massive nerve tract degeneration followed by neurological loss, paralysis and disabilities. Therapy of SCI patients with non-steroidal anti-inflammatory drugs (NSAIDs) help in diminishing secondary injury and lessen pain and swelling. However these drugs do not promote tissue repair. Therefore there is an unmet clinical need to develop technologies and therapeutic strategies that compensate loss of neuronal tissue, support and facilitate reestablishment of nerve tracks connectivity in the injured spinal cord. Recent progress in nerve regeneration indicates that a tissue engineering approach using soft tissue scaffolds, stem cells and neurotrophins, can lead to a partial therapy in animal models of SCI. Bioengineered scaffolds prepared by freeze casting technology provide an experimental tool for guidance of regenerating neuronal tracts and/or axons and therefore are useful for regeneration of injured spinal cord. In this engineering approach for scaffold preparation, temperature controlled directional solidification of an aqueous polymer(s) solution creates channels of different diameters that can direct axonal outgrowth of neurons populating the scaffold. In a previous study from our laboratory, such scaffolds promoted differentiation of neurons, a process facilitated by co-population of the scaffold’s channels with endothelial cells. “Green” plant proteins, such as soybean proteins, are becoming an attractive alternative source of natural polymers for a variety of biomedical applications including scaffold fabrication for neuronal tissue regeneration. In the present study, we developed a second generation of improved, microchanneled composite scaffolds from gelatin and soy protein isolate cross-linked with genipin (2 w/v %, 0.5 w/v %, 1 w/v %, respectively). The fabrication of these scaffolds by a controlled freeze drying technique, their mechanical properties (stiffness, ~3-4 kPa) as well as their uniform longitudinal channels of a diameter of ~30-55 µm is described. Preliminary biocompatibility experiments in 2D and 3D using the above mentioned scaffolds populated with either undifferentiated PC12 cells or nerve growth factor differentiated PC12 cells indicated partial biocompatibility of the scaffolds for neuronal growth. Improving the biocompatibility of these composite scaffolds is under investigation in our laboratory. / Bioengineering

Porous silica-based nanocomposites are promising ceramics, as they exhibit high specific surface area, highly porous network, and a surface that can be easily functionalized. This dissertation describes the results of a study on the formation and properties of porous silica nanoparticle-based composites, using techniques of freeze casting and sintering. Kaolinite platelets and silica nanorods were added into the nanoparticle system, and their effects on modifying the porous microstructures and physical properties were investigated. During freeze casting, homogeneous microstructures with highly interconnected porosity are fabricated. Kaolinite addition results in large and more interconnected pores, while added silica nanorods cause a pore morphology evolution from circular to elongated spherical pores with increasing aspect ratio. The specific surface areas (area/mass) of the particles are conserved during freeze casting and values for the resulting composites can be accurately predicted using the area and mass of the components assuming conservation of area. Both kaolinite platelets and silica nanorods effectively improved the strength of the freeze cast green composites as they distribute any applied stress over a larger portion of the sample. Upon sintering, added kaolinite is found to modify the sintering behavior of the silica nanoparticles and a transitioning interfacial phase is identified when sintering temperature is above 1250 °C. This new phase contributes to the further enhancement of strength and this strengthening effect depends on composition and initial solids loading. After sintering at 1250 °C for 1 h, a ceramic containing 10 vol% kaolinite and 8 vol% silica has a maximum strength while maintaining a ~69% porosity. The kaolinite-silica composites with lower solids loading exhibit faster sintering (e.g. larger shrinkage, more extensive thickening of the pore walls), which, in turn, results in a rapid increase in mechanical strength. Based on the understanding of the composite properties and the underlying principles, a novel method for creating nanocomposites with precisely controllable specific surface area is developed. With repeated nanoparticle suspension infiltration, freeze drying, and sintering, the specific surface area can be varied from less than one to well over 100 m2/g, demonstrating potential application as liquid membranes. / Ph. D.

There has been a lot of interest in Roselle (Hibiscus sabdariffa L.), called Bissap in Senegal, hibiscus recently because of consumer interest in nutraceutical products. However, beverages made from hibiscus have a short self-life due to anthocyanin and flavor degradation. The purpose of our study was first to assess the impacts of water, extraction procedure and origin on the anthocyanins of hibiscus extracts and secondly, to examine the impacts of freeze-drying on the anthocyanins and the volatiles compositions of hibiscus extracts. For the first experiment, a 2x3 factorial design was used with hibiscus calyces from Senegal and Egypt for the factor origin, distilled water and reformulated Dakar (Senegal) water for the second factor water, and then cold and hot extraction procedures were applied. For the second experiment, Senegalese hibiscus was extracted with hot and cold water and one part of each extract was freeze-dried. For both objectives, a ratio of 1:15 w/v (1 kilogram of calyces for 15 liters of water) were used. The time-temperature was 98°C / 30 min for hot and 22°C / 4 hours for cold extractions. The anthocyanins were determined using high performance liquid chromatography (HPLC). And the volatiles were measured using headspace-solid phase microextraction and gas chromatography-mass spectrometry (HS-SPME-GCMS). Origin and temperature as well as their interaction had significant effects on the anthocyanin contents, with respective p-values of 0.0036 and 0.0025 and 0.0002. Freeze-drying showed no effect on the anthocyanins in cold extracts. In contrast, a significant difference between the hot extract and its freeze-dried product was observed with a p-value of 0.0013. For the flavor compounds, the aroma profiles were different between cold and hot extracts and their instant powders. Globally the results of this study can help in the optimization when processing hibiscus derivatives. / MSLFS

The results of this investigation indicate: 1. The deterioration rate in the lateral direction of the uniaxially prestressed members subjected to the deep-seated type of freeze-thaw damage increased as the level of the compressive stress field increased. 2. Under all levels of uniaxial compression, cracks formed parallel to the direction of the applied stress field and in any plane parallel to this direction when the members were subjected to freeze-thaw damage. 3. The cracks are assumed to start at the boundary of a capillary within the aggregate and propagate through the aggregate to the aggegate- mortar interface. 4. Due to previous investigations, bond and mortar cracks are assumed to exist in the concrete. These cracks increase for increasing stress levels. 5. For the prestressed direction of any uniaxially prestressed member, there was a certain prestress level for which the change in length due to internal freeze-thaw damage equaled the change in length due to the applied prestressing force plus any longitudinal creep effects. This resulted in a total zero change in length. This zero change in length condition is called the "stress equilibrum condition" and the level of prestress which causes this condition is called the "prestress stability level." However, this condition can only last a short while before equilibrium is destroyed, since freeze-thaw daamage and and creep are continuously changing. / Master of Science

The freeze-drying process has been plagued with problems, such as long drying times and inefficiency. Microwave freeze-drying has proven its potential as way of reducing long drying times associated with freeze-drying, and as a result, there has been a considerable amount of work done to increase its use in industrial applications. However, it is not widely utilized for drying of pharmaceuticals, which appear to be better suited to microwave freeze-drying than foods. This paper discusses the results of applying microwave freeze-drying to an aqueous solution, as well as how various freezing rates affect freeze-drying characteristics. Results show that microwave freeze-drying can greatly reduce the time required to freeze-dry an aqueous solution while maintaining a high product quality. The investigation into the effects of different freezing conditions shows that different physical characteristics in the dried product can be achieved through varying the freezing rate. / Master of Science

A Chamomilla recutita L. é uma das plantas medicinais mais cultivadas no Brasil e no mundo. Os extratos da C. recutita são de interesse para as indústrias farmacêuticas e cosméticas, visto que estes apresentam atividades anti-inflamatória, antioxidante e adstringente. A ação terapêutica do extrato pode ser mais pronunciada que a ação terapêutica de um de seus ativos isolados. No entanto, a incorporação de um extrato em uma formulação pode ser difícil devido à baixa estabilidade dos extratos, bem como à possibilidade de gerarem instabilidade das formulações. Microencapsulando o extrato com um carreador é possível aumentar estabilidade do extrato quanto evitar instabilidade na formulação. Além disso, a microencapsulação é capaz de fornecer outras vantagens, como uma liberação controlada. Dois processos foram estudados como alternativas para a microencapsulação do óleo essencial e do extrato hidroalcoólico da C. recutita usando quitosana como carreador: o spray drying e o spray freeze drying. Planejamentos fatorais foram utilizados para determinar os fatores que mais influenciaram no diâmetro médio das micropartículas, eficiência de encapsulação e teor dos marcadores e rendimento do processo. A apigenina e a apigenina-7-glicosídeo foram usadas como marcadores do extrato hidroalcoólico e o óxido de bisabolol A foi usado como marcador do óleo essencial. Os processos de spray drying e spray freeze drying dos dois extratos foram otimizados e as micropartículas resultantes foram caracterizadas com relação ao diâmetro médio, rendimento do processo, teor e eficiência de encapsulação dos marcadores, atividade antioxidante in vitro, densidade, índice de Carr, fator de Hausner, umidade, morfologia, perfil de liberação n vitro e estabilidade. Os resultados mostraram que o processo de spray drying apresentou os melhores resultados para eficiência de encapsulação, com valores de aproximadamente 98%, 95% e 80% para apigenina, apigenina-7-glicosídeo e óxido de bisabolol A, respectivamente. As eficiências de encapsulação obtidas no processo de spray freeze drying foram de aproximadamente 59%, 58% e 38% para os mesmos marcadores, respectivamente. As micropartículas produzidas por spray freeze drying apresentaram formato irregular e poroso, enquanto as produzidas por spray drying apresentaram formato esférico e superfícies mais lisas, sem poros ou fissuras. Ao contrário do que ocorreu com o extrato hidroalcoólico, a perda do marcador do óleo foi elevada no processo de spray drying, com teor final de 35%. Os teores dos marcadores ficaram acima de 80% para o processo de spray freeze drying do óleo e acima de 90% para o extrato hidroalcoólico. As micropartículas produzidas por spray drying do extrato hidroalcoólico e do óleo e por spray freeze drying do extrato hidroalcoólico e do óleo apresentaram diâmetro médio de 5,1 ?m, 5,0 ?m, 31,0 ?m e 96,4 ?m, respectivamente. Ensaios de liberação in vitro mostraram que as micropartículas foram capazes de sustentar a liberação dos respectivos marcadores. Os estudos de permeação in vitro das micropartículas produzidas por spray drying do extrato hidroalcoólico também mostraram que estas foram capazes de sustentar a liberação. A microencapsulação proporcionou em todos os casos um aumento considerável da estabilidade. As micropartículas produzidas por spray drying do extrato hidroalcoólico apresentaram teores de marcadores no mínimo 50% maiores que o extrato puro após 90 dias. O spray freeze drying se mostrou como a melhor alternativa para produção de micropartículas de quitosana contendo o óleo essencial de C. recutita, enquanto o processo de spray drying se mostrou como uma ótima alternativa para microencapsulação do extrato hidroalcoólico da C. recutita. / Chamomilla recutita L. is one of the most cultivated medicinal plants in Brazil and around the world. Its extracts are important to both the pharmaceutical and cosmetics industries due to its therapeutic applications, such as an anti-inflammatory, antioxidant, and astringent. The therapeutic effects of an extract may be more pronounced than those of an isolated active compound. However, the incorporation of an extract in a formulation is difficult due to the low stability of extracts and the potential instabilities they may cause in formulations. Microencapsulating an extract in a carrier is a potential way of increasing the stability of an extract and avoiding instabilities in a formulation. Compound microencapsulation also brings other advantages, such as controlled release rates. Two processes were studied as alternatives to microencapsulating C. recutita essential oil and C. recutita hydroalcoholic extract using chitosan as a carrier: spray drying and spray freeze drying. Factorial designs were used to determine which process factors most influence the mean diameter, encapsulation efficiency and content of the chemical markers, and process yield. Apigenin and apigenin-7-glucoside were used as chemical markers for the hydroalcoholic extract and bisabolol oxide A was used as the chemical marker for the essential oil. The spray drying and spray freeze drying processes for both the oil and hydroalcoholic extract were optimized and the resulting microparticles were further characterized to determine mean diameter, process yield, marker encapsulation efficiency and content, in vitro antioxidant activity, density, Carr index, Hausner factor, water content, morphology, in vitro release profiles and stability. The results showed spray drying had the best encapsulation efficiency results, with about 98%, 95% e 80% of the apigenin, apigenin-7-glucoside and bisabolol oxide A content, respectively, inside the microparticles. The encapsulation efficiencies obtained in the spray freeze drying process were about 59%, 58% e 38% for the same chemical markers, respectively. Microparticles produced by spray freeze drying were irregular and porous, whereas microparticles produced by spray drying were spherical and fairly smooth, without porous or cracks. Contrary to what happened with the hydroalcoholic extract, oil marker content was low for spray dried microparticles, with final content at 35%. Chemical markers contents were above 80% for the oil and above 90% for the hydroalcoholic extract in spray freeze dried microparticles. Spray dried microparticles containing extract and oil and spray freeze dried microparticles containing extract and oil had mean diameter of 5.1 ?m, 5.0 ?m, 31.0 ?m and 96.4 ?m, respectively. In vitro release profiles showed all microparticles were able to sustain their respective marker release rates. In vitro permeation studies of spray dried microparticles containing hydroalcooholic extract also showed sustained release rates for the corresponding markers. Microencapsulation also provided considerable increase in C. recutita hydroalcoholic extract stability and C. recutita essential oil stability. After 90 days spray dried microparticles containing hydroalcoholic extract presented marker content 50% higher than the pure hydroalcoholic extract. Spray freeze drying was the best alternative to produce chitosan microparticles containing C. recutita essential oil, while spray drying was shown to be an excellent way to microencapsulate C. recutita hydroalcoholic extract in chitosan.