The transdermal delivery route has become a popular alternative to more conventional routes, such as oral administration, but has not yet reached its full potential (Prausnitz & Langer, 2008:1261). Although the transdermal route proves to have several advantages over the conventional route, the greatest challenge is to overcome the effective barrier of the skin (Jepps et al., 2012:153). The permeation of the active pharmaceutical ingredient (API) through the skin is a complex, multi-step process and therefore predicting the permeability of the API is difficult (Jepps et al., 2012:153; Williams, 2003:30). Various approaches have been developed to overcome the skin barrier and it is recognised that the nature of the vehicle in which the API is applied plays a significant role in promoting transdermal delivery (Foldvari, 2000:417). It is important to consider the fate of the formulation ingredients and the API after application and how this changes the composition of the formulation on the skin when developing a vehicle for transdermal delivery (Lane et al., 2012:496; Otto et al., 2009:2). Wiechers (2012) proposed the Skin Delivery Gap (SDG) as an indicator for the permeability of an API. An API with a SDG < 1 will readily permeate the skin, whilst an SDG > 1 indicates a more complex delivery system is required. The partitioning of the API between the skin and the formulation is influenced by the formulation and by altering the formulation properties it is possible to manipulate the transdermal delivery of the API. The relative polarity index (RPI), based on the octanol-water partition coefficient (log P) of the stratum corneum, formulation and the API, was initially developed by Wiechers as a tool for developing formulations with an optimal polarity, to ensure the transdermal delivery of at least 50% of the API (Lane et al., 2012:498; Wiechers, 2008:94; Wiechers et al., 2004:174). The use of log P as an indicator of polarity was considered impractical by Hansen (2013) and acknowledged by both Wiechers and Abbott, who consequently developed the Formulating for Efficacy™ (FFE™) software which uses Hansen solubility parameters (HSP) instead of log P to indicate polarity (Hansen, 2013). The FFE™ calculates HSP distances, known as gaps, between the skin, API and the formulation to indicate the solubility of the different components in each other. A smaller HSP gap indicates a high solubility. The FFE™ enables the formulator to develop a formulation with a good balance between the active-formulation gap (AFG) and the skin-formulation gap (SFG) to ensure sufficient diffusion of the API into the skin. The FFE™ software was used to develop formulations containing 1.5% atropine as a model drug. Formulations of different polarity (optimised towards the stratum corneum, more hydrophilic and more lipophilic) were developed to determine the effect of the polarity of the formulation and the relevant HSP gaps on the transdermal delivery of the API. The same formulations were utilised for atropine sulphate to determine the effect the salt form has on the transdermal delivery of the API compared to the base compound. The log P and octanol-buffer partition coefficient (log D) of both atropine and atropine sulphate were determined. Log D is a more reliable indicator of distribution compared to log P, since, it considers the degree of ionisation of the API (Ashford, 2007:294). The log P and log D of atropine (0.22 and -1.26) and atropine sulphate (-1.32 and -1.23) both predicted poor skin penetration (Brown et al., 2005:177). The aqueous solubility of atropine (0.9 mg/ml) also predicted limited transdermal delivery, while the solubility of atropine in phosphate buffer solution (PBS pH 7.4) (5.8 mg/ml) indicated favourable permeation (Naik et al., 2000:321). The high degree of ionisation of the API (99.68 %), at pH 7.4, predicts only a small amount will penetrate the skin (Barry, 2007:576). The membrane release study confirmed the API was released from the different formulations and subsequently skin diffusion studies were conducted, followed by tape stripping after 12 h, to determine which formulation resulted in the highest transdermal delivery of the API. The atropine hydrophilic formulation released the highest percentage of API after 6 h (13.930%). This was explained by the low affinity the lipophilic atropine has towards the hydrophilic formulation (Otto et al., 2009:9). The highest percentage transdermal delivery (0.065%) was observed with the lipophilic formulation containing atropine. The higher SFG compared to the AFG of the lipophilic formulation initially predicted poor transdermal delivery, but when considering the HSP profile and molar volume of the different ingredients, it was observed the dimethyl isosorbide (DMI) penetrated and provided a desirable environment for the API in the skin. The residual formulation (containing less DMI and more polyethylene glycol 400 (PEG 8) and liquid paraffin) was less desirable for the API and was therefore forced out of the formulation (Abbott, 2012:219). Both these factors contributed to the high transdermal delivery of atropine from the lipophilic formulation. The atropine sulphate hydrophilic formulation had the highest percentage in the stratum corneum-epidermis (0.29 μg/ml) and the hydrophilic formulation of both atropine and atropine sulphate had the highest concentration in the epidermis-dermis (both 0.55 μg/ml). The hydrophilic formulations had the lowest driving force provided by the AFG and the only driving force for the API to leave the formulation was the concentration gradient. These formulations had the lowest transdermal delivery which indicates the API had not fully traversed through the skin after 12 h. According to Wiechers, a minimised SFG would indicate the formulation is optimised towards the stratum corneum and should essentially deliver the highest percentage of API through the skin. The results obtained are contrary to this belief and it is concluded that the total HSP profile and the molar volume of the formulation and the API should be considered when developing a formulation with optimal transdermal delivery rather than just the SFG. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

The transdermal delivery route has become a popular alternative to more conventional routes, such as oral administration, but has not yet reached its full potential (Prausnitz & Langer, 2008:1261). Although the transdermal route proves to have several advantages over the conventional route, the greatest challenge is to overcome the effective barrier of the skin (Jepps et al., 2012:153). The permeation of the active pharmaceutical ingredient (API) through the skin is a complex, multi-step process and therefore predicting the permeability of the API is difficult (Jepps et al., 2012:153; Williams, 2003:30). Various approaches have been developed to overcome the skin barrier and it is recognised that the nature of the vehicle in which the API is applied plays a significant role in promoting transdermal delivery (Foldvari, 2000:417). It is important to consider the fate of the formulation ingredients and the API after application and how this changes the composition of the formulation on the skin when developing a vehicle for transdermal delivery (Lane et al., 2012:496; Otto et al., 2009:2). Wiechers (2012) proposed the Skin Delivery Gap (SDG) as an indicator for the permeability of an API. An API with a SDG < 1 will readily permeate the skin, whilst an SDG > 1 indicates a more complex delivery system is required. The partitioning of the API between the skin and the formulation is influenced by the formulation and by altering the formulation properties it is possible to manipulate the transdermal delivery of the API. The relative polarity index (RPI), based on the octanol-water partition coefficient (log P) of the stratum corneum, formulation and the API, was initially developed by Wiechers as a tool for developing formulations with an optimal polarity, to ensure the transdermal delivery of at least 50% of the API (Lane et al., 2012:498; Wiechers, 2008:94; Wiechers et al., 2004:174). The use of log P as an indicator of polarity was considered impractical by Hansen (2013) and acknowledged by both Wiechers and Abbott, who consequently developed the Formulating for Efficacy™ (FFE™) software which uses Hansen solubility parameters (HSP) instead of log P to indicate polarity (Hansen, 2013). The FFE™ calculates HSP distances, known as gaps, between the skin, API and the formulation to indicate the solubility of the different components in each other. A smaller HSP gap indicates a high solubility. The FFE™ enables the formulator to develop a formulation with a good balance between the active-formulation gap (AFG) and the skin-formulation gap (SFG) to ensure sufficient diffusion of the API into the skin. The FFE™ software was used to develop formulations containing 1.5% atropine as a model drug. Formulations of different polarity (optimised towards the stratum corneum, more hydrophilic and more lipophilic) were developed to determine the effect of the polarity of the formulation and the relevant HSP gaps on the transdermal delivery of the API. The same formulations were utilised for atropine sulphate to determine the effect the salt form has on the transdermal delivery of the API compared to the base compound. The log P and octanol-buffer partition coefficient (log D) of both atropine and atropine sulphate were determined. Log D is a more reliable indicator of distribution compared to log P, since, it considers the degree of ionisation of the API (Ashford, 2007:294). The log P and log D of atropine (0.22 and -1.26) and atropine sulphate (-1.32 and -1.23) both predicted poor skin penetration (Brown et al., 2005:177). The aqueous solubility of atropine (0.9 mg/ml) also predicted limited transdermal delivery, while the solubility of atropine in phosphate buffer solution (PBS pH 7.4) (5.8 mg/ml) indicated favourable permeation (Naik et al., 2000:321). The high degree of ionisation of the API (99.68 %), at pH 7.4, predicts only a small amount will penetrate the skin (Barry, 2007:576). The membrane release study confirmed the API was released from the different formulations and subsequently skin diffusion studies were conducted, followed by tape stripping after 12 h, to determine which formulation resulted in the highest transdermal delivery of the API. The atropine hydrophilic formulation released the highest percentage of API after 6 h (13.930%). This was explained by the low affinity the lipophilic atropine has towards the hydrophilic formulation (Otto et al., 2009:9). The highest percentage transdermal delivery (0.065%) was observed with the lipophilic formulation containing atropine. The higher SFG compared to the AFG of the lipophilic formulation initially predicted poor transdermal delivery, but when considering the HSP profile and molar volume of the different ingredients, it was observed the dimethyl isosorbide (DMI) penetrated and provided a desirable environment for the API in the skin. The residual formulation (containing less DMI and more polyethylene glycol 400 (PEG 8) and liquid paraffin) was less desirable for the API and was therefore forced out of the formulation (Abbott, 2012:219). Both these factors contributed to the high transdermal delivery of atropine from the lipophilic formulation. The atropine sulphate hydrophilic formulation had the highest percentage in the stratum corneum-epidermis (0.29 μg/ml) and the hydrophilic formulation of both atropine and atropine sulphate had the highest concentration in the epidermis-dermis (both 0.55 μg/ml). The hydrophilic formulations had the lowest driving force provided by the AFG and the only driving force for the API to leave the formulation was the concentration gradient. These formulations had the lowest transdermal delivery which indicates the API had not fully traversed through the skin after 12 h. According to Wiechers, a minimised SFG would indicate the formulation is optimised towards the stratum corneum and should essentially deliver the highest percentage of API through the skin. The results obtained are contrary to this belief and it is concluded that the total HSP profile and the molar volume of the formulation and the API should be considered when developing a formulation with optimal transdermal delivery rather than just the SFG. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

No description available.

Adesivos modernos são misturas complexas de monômeros resinosos hidrofílicos e hidrofóbicos dissolvidos em combinações de água/solvente. A inclusão de monômeros altamente hidrofílicos nos sistemas adesivos está transformando-os em membranas permeáveis que são altamente susceptíveis aos efeitos de degradação da água. Desenvolver formulações adesivas que promovem uma melhor penetração de componentes hidrofóbicos dentro da matriz dentinária é de grande importância. O método mais válido para se avaliar o processo de degradação in vitro é a armazenagem dos espécimes em água. Neste estudo avaliamos através do microcisalhamento com delimitação da área adesiva de 0,8 mm, a resistência adesiva de 3 adesivos experimentais com diferentes graus de hidrofilia. Os fatores de variação foram 2: o tipo de adesivo experimental utilizado, em 4 níveis ( Bis-GMA, Bis-EMA/ Bis-GMA, PBH, Single Bond) e o período de armazenamento, em 3 níveis (1 dia, 7 dias, 90 dias), totalizando 12 níveis de variação. Foram confeccionadas 120 superfícies de dentina de 30 terceiros molares extraídos, totalizando um n= 10. O modelo estatístico escolhido foi o teste paramétrico de ANOVA de dois fatores independentes. Os adesivos experimentais apresentaram valores na faixa de 11.31 a 12.96 MPa, sendo que o PBH apresentou os menores valores de resistência adesiva, Bis-GMA os maiores e Bis-EMA/Bis-GMA valores intermediários, enquanto que o grupo Controle está dentro de uma faixa média de 24 MPa. Através da MEV, observamos que os adesivos experimentais não formaram camada híbrida, embora tenha ocorrido a penetração nos túbulos dentinários e a formação de tags de resina. Provavelmente, a menor hidrofilicidade dos adesivos não permitiu a penetração dos adesivos na matriz de colágeno úmida para provocar uma hibridização levando a resistências adesivas bem menores que o adesivo controle. Com o presente estudo, concluímos que adesivos dentinários com componentes monoméricos hidrofóbicos, embora formem tags de resina, se tornam incapazes de penetrar nas fibras colágenas e formar camada híbrida e consequentemente têm baixa resistência adesiva e que também tende a decair com o tempo. / The most recent adhesives systems have fewer steps required for bonding to simplify use and hopefully reduce technique sensitivity. A trend in adhesive dentistry is providing simpler and faster adhesives. Single bottle adhesives are complex mixtures of hydrophilic and hydrophobic resin monomers dissolved in water/solvent combinations. In this study we evaluate by microshear test 3 experimental adhesives with different degree of hydrophilicity after 1, 7 and 90 days.The variation factors were 2: the type of the adhesive used, at 4 levels (Bis-GMA, Bis-EMA/Bis-GMA, PBH, Single Bond) and the period of storage, in 3 levels (1 day, 7 days, 90 days), totalizing 12 levels of variation. The etch-and-rinse experimental adhesive systems were formulated by FGM, Joinville, SC, BR. The experimental units were confectioned on 120 dentine surfaces of 30 third extracted molar, totalizing n= 10. The specimens were stored in water distilled and divided in 4 groups of 10 specimens in accordance with the type of used monomer, being that each tooth origin 4 specimens. The delimitation of the adhesive area was used, made with adhesive ribbon double face with 1 circular perforation lined up of 0,8 mm of diameter made with a rubber sheet perforator in each specimen, being used for each one tygon tubing with light of 0,8 mm. The fractures were classified as adhesive, coesive in dentine, coesive in resin and mixing. Using the parametric test of variance analyses (ANOVA) of two independent factors, we observed that the experimental adhesives showed values in the range of 11.31 a 12.96 MPa, as the PBH showed the lowest values of resistance, Bis-GMA the highest and Bis-EMA/Bis-GMA intermediary values, and the control group in the range of 24 MPa. Dentin adhesives with hydrophobic monomeric components can form resin tags, but they are disable to penetrate colagen fibers and form hybrid layers and consequently have low bond resistance that falls with time.

Adesivos modernos são misturas complexas de monômeros resinosos hidrofílicos e hidrofóbicos dissolvidos em combinações de água/solvente. A inclusão de monômeros altamente hidrofílicos nos sistemas adesivos está transformando-os em membranas permeáveis que são altamente susceptíveis aos efeitos de degradação da água. Desenvolver formulações adesivas que promovem uma melhor penetração de componentes hidrofóbicos dentro da matriz dentinária é de grande importância. O método mais válido para se avaliar o processo de degradação in vitro é a armazenagem dos espécimes em água. Neste estudo avaliamos através do microcisalhamento com delimitação da área adesiva de 0,8 mm, a resistência adesiva de 3 adesivos experimentais com diferentes graus de hidrofilia. Os fatores de variação foram 2: o tipo de adesivo experimental utilizado, em 4 níveis ( Bis-GMA, Bis-EMA/ Bis-GMA, PBH, Single Bond) e o período de armazenamento, em 3 níveis (1 dia, 7 dias, 90 dias), totalizando 12 níveis de variação. Foram confeccionadas 120 superfícies de dentina de 30 terceiros molares extraídos, totalizando um n= 10. O modelo estatístico escolhido foi o teste paramétrico de ANOVA de dois fatores independentes. Os adesivos experimentais apresentaram valores na faixa de 11.31 a 12.96 MPa, sendo que o PBH apresentou os menores valores de resistência adesiva, Bis-GMA os maiores e Bis-EMA/Bis-GMA valores intermediários, enquanto que o grupo Controle está dentro de uma faixa média de 24 MPa. Através da MEV, observamos que os adesivos experimentais não formaram camada híbrida, embora tenha ocorrido a penetração nos túbulos dentinários e a formação de tags de resina. Provavelmente, a menor hidrofilicidade dos adesivos não permitiu a penetração dos adesivos na matriz de colágeno úmida para provocar uma hibridização levando a resistências adesivas bem menores que o adesivo controle. Com o presente estudo, concluímos que adesivos dentinários com componentes monoméricos hidrofóbicos, embora formem tags de resina, se tornam incapazes de penetrar nas fibras colágenas e formar camada híbrida e consequentemente têm baixa resistência adesiva e que também tende a decair com o tempo. / The most recent adhesives systems have fewer steps required for bonding to simplify use and hopefully reduce technique sensitivity. A trend in adhesive dentistry is providing simpler and faster adhesives. Single bottle adhesives are complex mixtures of hydrophilic and hydrophobic resin monomers dissolved in water/solvent combinations. In this study we evaluate by microshear test 3 experimental adhesives with different degree of hydrophilicity after 1, 7 and 90 days.The variation factors were 2: the type of the adhesive used, at 4 levels (Bis-GMA, Bis-EMA/Bis-GMA, PBH, Single Bond) and the period of storage, in 3 levels (1 day, 7 days, 90 days), totalizing 12 levels of variation. The etch-and-rinse experimental adhesive systems were formulated by FGM, Joinville, SC, BR. The experimental units were confectioned on 120 dentine surfaces of 30 third extracted molar, totalizing n= 10. The specimens were stored in water distilled and divided in 4 groups of 10 specimens in accordance with the type of used monomer, being that each tooth origin 4 specimens. The delimitation of the adhesive area was used, made with adhesive ribbon double face with 1 circular perforation lined up of 0,8 mm of diameter made with a rubber sheet perforator in each specimen, being used for each one tygon tubing with light of 0,8 mm. The fractures were classified as adhesive, coesive in dentine, coesive in resin and mixing. Using the parametric test of variance analyses (ANOVA) of two independent factors, we observed that the experimental adhesives showed values in the range of 11.31 a 12.96 MPa, as the PBH showed the lowest values of resistance, Bis-GMA the highest and Bis-EMA/Bis-GMA intermediary values, and the control group in the range of 24 MPa. Dentin adhesives with hydrophobic monomeric components can form resin tags, but they are disable to penetrate colagen fibers and form hybrid layers and consequently have low bond resistance that falls with time.

O uso do bagaço de cana-de-açúcar, um subproduto da produção sucroalcooleira, ainda está hoje atrelado diretamente à produção de energia com sua queima nas usinas, um uso que é pouco nobre, considerando-se a grande diversidade de compostos químicos presentes neste tipo de material. A possibilidade de valorização desta matéria-prima lignocelulósica está ligada a realização de etapas de separação das principais frações de compostos, a celulose, as hemiceluloses e a lignina. Neste contexto, as deslignificações organossolve, etapa de remoção da lignina através da solubilização da mesma em soluções orgânicas, tem grande potencial de uso, visto que nestas pode-se recuperar tanto a polpa como o licor de polpação para posterior uso. Assim, verifica-se que a solubilidade da lignina é o fator que diferencia a utilização de um dado solvente orgânico em uma deslignificação organossolve. Desta maneira, pode-se utilizar o conceito de parâmetros de solubilidade para a escolha de um melhor solvente para o processo. Neste trabalho, verificou-se a relação entre a deslignificação organossolve e a distância e afinidade de um solvente com a esfera de solubilidade de Hansen para a lignina de bagaço de cana-de-açúcar. Verificou-se que os parâmetros de solubilidade de Hansen para a lignina verificados na literatura não apresentam boa correlação com os dados de deslignificação, porém, uma nova esfera de solubilidade foi desenvolvida, na qual verificou-se um coeficiente de determinação de 0,93856, em detrimento de um de 0,72074 para a esfera de solubilidade verificada na literatura. Concluiu-se que o modelo desenvolvido possuía como principal diferença com relação ao modelo obtido por Hansen e Björkman para a lignina, um parâmetro de solubilidade para interações intermoleculares polares (&delta;p) inferior e um parâmetro de solubilidade para a capacidade de realização de ligações de hidrogênio (&delta;h) bem superior, porém mantendo o mesmo parâmetro de solubilidade total (&delta;). Confirmou-se a relação entre a deslignificação e os valores de distância e de afinidade obtidos neste trabalho, com a realização de deslignificações usando misturas ternárias e quaternárias com solventes de baixo custo e/ou excedentes no mercado (etanol, glicerol e 2-butanol, além de água). Concluiu-se que apesar da esfera de solubilidade desenvolvida permitir melhor ajuste dos dados, não se pode afirmar que esta é com certeza a esfera real para a lignina. / The use of sugarcane bagasse, a by-product of sugar and ethanol production, is still linked today directly to energy production with its burning in power plants, a use which is not very noble, considering the great diversity of chemical compounds present in the lignocellulosic matrix. The possibility of better use of lignocellulosic feedstock is linked to steps of separation of their main fractions, cellulose, hemicelluloses and lignin. In this context, organosolv delignification, in which lignin is removed by the solubilization in organic solutions have great potential, since both pulps and the pulping liquor can be recovered for later use. Thus, since the solubility of lignin is the factor that differentiates the use of a given organic solvent in an organosolv delignification, the concept of solubility parameters can be used for the selection of the organic solvent. In this dissertation the relationship between the distance and the affinity of a solvent with the Hansen sphere of solubility for lignin from bagasse cane sugar and organosolv delignification were studied. It was found that the Hansen solubility parameters for lignin found in the literature do not present a good correlation with delignification data. Thus a new sphere of solubility was developed, with a determination coefficient of 0.93856, over a determination coefficient of 0.72074 for the sphere of solubility found in the literature. It was concluded that the main differences between the developed model and the model obtained by Hansen and Björkman for lignin were a lower solubility parameter for polar intermolecular interactions (&delta;p) and a higher solubility parameter for hydrogen bonds (&delta;h), however keeping the same total solubility parameter (&delta;). The relationship between delignification and the values of the distance and affinity obtained in this work were confirmed with the attainment of organosolv delignification using tertiary and quaternary mixtures of solvents with low cost and/or availability in the market (ethanol, glycerol and 2-butanol, in addition to water). It was concluded that although the developed solubility sphere allowed a better fit of the data, it cannot be stated with certainty that this is the real sphere for lignin.

A extração por solvente é o método mais eficiente para recuperação do óleo residual de fibra prensada de palma (FPP), o qual pode conter um teor de carotenoides até oito vezes superior ao encontrado no óleo de palma bruto. Neste contexto, a escolha de potenciais solventes ou misturas de solventes torna-se essencial, pois elas podem resultar no efeito sinérgico de extração de óleo e carotenoides promovendo uma maior recuperação destes compostos de interesse. Dessa forma, o presente estudo objetivou a utilização de misturas binárias de solventes hidrocarbonetos e alcoólicos, a fim de promover a maior recuperação de um óleo de FPP rico em carotenoides. Para tanto, as composições das misturas compostas por hidrocarboneto (hexano, heptano e ciclohexano) e álcoois de cadeia curta (etanol e isopropanol) foram definidas a partir do cálculo da distância soluto-solvente (Ra) entre as misturas de solventes e o soluto &beta;-caroteno. Os experimentos de extração foram conduzidos a 60 ± 2°C em um intervalo de tempo de 5 horas em extrator em batelada, utilizando os solventes hexano, heptano, ciclohexano, etanol e isopropanol e suas respectivas misturas, e a 55 ± 3 °C e um intervalo de tempo de 1 hora e 30 minutos, em coluna empacotada de leito fixo, utilizando hexano, etanol, isopropanol e suas respectivas misturas. Os resultados dos experimentos de extração, em batelada na razão mássica sólido:solvente de 1:7, indicaram que hexano e a mistura compreendida por heptano e isopropanol, extraíram o maior conteúdo de lipídeos, em torno de 80 % (em massa), enquanto que os demais solventes puros e misturas de solventes permitiram a obtenção de rendimentos de extração de óleo em torno de 70 % (em massa). Apesar dos solventes ciclohexano e hexano apresentarem a maior extração de carotenoides, o teor deste componente apresentou-se levemente inferior quando foram utilizadas as misturas binárias de solventes. Os maiores rendimentos de extração de óleo de FPP em coluna, na razão mássica sólido:solvente de 1:4, deram-se com o emprego de etanol e da mistura compreendida por hexano e isopropanol, em torno de 66 % (em massa), porém o conteúdo de carotenoides obtido foi o mesmo, independentemente do solvente ou misturas de solventes empregadas. O perfil de carotenoides analisados por UPLC/MS apresentou elevado conteúdo de &beta;-caroteno extraído majoritariamente por hexano, enquanto que o maior conteúdo de &alpha;-caroteno foi obtido pela mistura de hexano e etanol, por último, etanol extraiu o maior conteúdo de licopeno. Nesta dissertação não foi observado, de forma expressiva, o sinergismo de extração de óleo de FPP rico em carotenoides com o emprego de misturas de solventes definidas a partir da estimativa dos Parâmetros de Solubilidade de Hansen (PSH) e cálculo da Ra. No entanto, é possível inferir os solventes hidrocarbonetos e suas misturas com os álcoois de cadeia curta, etanol e isopropanol, demonstraram boa habilidade em extrair óleo de FPP rico em carotenoides, mantendo sua composição em ácidos graxos e acidez livre relativamente constantes podendo, assim, serem indicados para operações de extração de óleo de FPP. As misturas de solventes empregadas nos experimentos de extração resultaram em considerável rendimento de óleo de FPP, rico em carotenoides totais mostrando que a substituição parcial de solventes hidrocarbonetos por álcoois de cadeia curta é possível. / Solvent extraction is the most efficient method for recovering palm pressed fiber (PPF) residual oil, which may contain up to eight times the carotenoid content of that found in crude palm oil. In this context, the choice of potential solvents or solvent mixtures becomes essential as they may result in the synergistic effect of extracting oil and carotenoids promoting further recovery of these compounds of interest. Thus, the present study aimed at the use of binary mixtures of hydrocarbon and alcoholic solvents, in order to promote the higher recovery of a carotenoid-rich PPF oil. The compositions of the mixtures composed of hydrocarbons (hexane, heptane, and cyclohexane) and short chain alcohols (ethanol and isopropanol) were defined from the calculation of the solute-solvent distance (Ra) between the solvent mixtures and the solute &beta;-carotene. The extraction experiments were conducted at 60 ± 2 °C during 5 hours in a batch extractor, using the hexane, heptane, cyclohexane, ethanol and isopropanol solvents and their mixtures, and at 55 ± 3 °C and a time interval of 1 hour and 30 minutes in a packed bed column using hexane, ethanol, isopropanol and their mixtures. The results of the batch extraction experiments at the solid: solvent mass ratio of 1:7 indicated that hexane and the mixture comprised of heptane and isopropanol extracted the highest lipid content, around 80 % (by mass), while that the other pure solvents and solvent mixtures allowed to obtain oil extraction yields around 70 % (by mass). Although the solvents cyclohexane and hexane had the highest extraction of carotenoids, the content of this component was slightly lower when the binary solvent mixtures were used. The higher yields of oil extraction of PPF in the column in the solid: solvent mass ratio of 1:4 were given by using ethanol and the mixture comprised of hexane and isopropanol, around 66 % (by mass), but the carotenoids content obtained was the same regardless of the solvent or solvent mixtures employed. The profile of carotenoids analyzed in UPLC/MS showed a high content of &beta;-carotene extracted mainly by hexane, while the highest content of &alpha;-carotene was obtained by the mixture of hexane and ethanol, finally, ethanol extracted the highest content of lycopene. In this dissertation, the synergism of extraction of PPF oil rich in carotenoids was not observed within the use of solvent mixtures defined from the estimation of Hansen Solubility Parameters (HSP) and calculation of Ra. However, it is possible to infer that the hydrocarbon solvents and their mixtures with the short-chain alcohols, ethanol, and isopropanol, demonstrated good ability to extract of PPF oil rich in carotenoids, maintaining its composition in fatty acids and free acidity constant being indicated for PPF oil extraction operations. The use of the solvent mixtures resulted in a considerable extraction yield of PPF oil, rich in total carotenoids showing that the partial replacement of hydrocarbon solvents by short chain alcohols is possible.

A extração por solvente é o método mais eficiente para recuperação do óleo residual de fibra prensada de palma (FPP), o qual pode conter um teor de carotenoides até oito vezes superior ao encontrado no óleo de palma bruto. Neste contexto, a escolha de potenciais solventes ou misturas de solventes torna-se essencial, pois elas podem resultar no efeito sinérgico de extração de óleo e carotenoides promovendo uma maior recuperação destes compostos de interesse. Dessa forma, o presente estudo objetivou a utilização de misturas binárias de solventes hidrocarbonetos e alcoólicos, a fim de promover a maior recuperação de um óleo de FPP rico em carotenoides. Para tanto, as composições das misturas compostas por hidrocarboneto (hexano, heptano e ciclohexano) e álcoois de cadeia curta (etanol e isopropanol) foram definidas a partir do cálculo da distância soluto-solvente (Ra) entre as misturas de solventes e o soluto &beta;-caroteno. Os experimentos de extração foram conduzidos a 60 ± 2°C em um intervalo de tempo de 5 horas em extrator em batelada, utilizando os solventes hexano, heptano, ciclohexano, etanol e isopropanol e suas respectivas misturas, e a 55 ± 3 °C e um intervalo de tempo de 1 hora e 30 minutos, em coluna empacotada de leito fixo, utilizando hexano, etanol, isopropanol e suas respectivas misturas. Os resultados dos experimentos de extração, em batelada na razão mássica sólido:solvente de 1:7, indicaram que hexano e a mistura compreendida por heptano e isopropanol, extraíram o maior conteúdo de lipídeos, em torno de 80 % (em massa), enquanto que os demais solventes puros e misturas de solventes permitiram a obtenção de rendimentos de extração de óleo em torno de 70 % (em massa). Apesar dos solventes ciclohexano e hexano apresentarem a maior extração de carotenoides, o teor deste componente apresentou-se levemente inferior quando foram utilizadas as misturas binárias de solventes. Os maiores rendimentos de extração de óleo de FPP em coluna, na razão mássica sólido:solvente de 1:4, deram-se com o emprego de etanol e da mistura compreendida por hexano e isopropanol, em torno de 66 % (em massa), porém o conteúdo de carotenoides obtido foi o mesmo, independentemente do solvente ou misturas de solventes empregadas. O perfil de carotenoides analisados por UPLC/MS apresentou elevado conteúdo de &beta;-caroteno extraído majoritariamente por hexano, enquanto que o maior conteúdo de &alpha;-caroteno foi obtido pela mistura de hexano e etanol, por último, etanol extraiu o maior conteúdo de licopeno. Nesta dissertação não foi observado, de forma expressiva, o sinergismo de extração de óleo de FPP rico em carotenoides com o emprego de misturas de solventes definidas a partir da estimativa dos Parâmetros de Solubilidade de Hansen (PSH) e cálculo da Ra. No entanto, é possível inferir os solventes hidrocarbonetos e suas misturas com os álcoois de cadeia curta, etanol e isopropanol, demonstraram boa habilidade em extrair óleo de FPP rico em carotenoides, mantendo sua composição em ácidos graxos e acidez livre relativamente constantes podendo, assim, serem indicados para operações de extração de óleo de FPP. As misturas de solventes empregadas nos experimentos de extração resultaram em considerável rendimento de óleo de FPP, rico em carotenoides totais mostrando que a substituição parcial de solventes hidrocarbonetos por álcoois de cadeia curta é possível. / Solvent extraction is the most efficient method for recovering palm pressed fiber (PPF) residual oil, which may contain up to eight times the carotenoid content of that found in crude palm oil. In this context, the choice of potential solvents or solvent mixtures becomes essential as they may result in the synergistic effect of extracting oil and carotenoids promoting further recovery of these compounds of interest. Thus, the present study aimed at the use of binary mixtures of hydrocarbon and alcoholic solvents, in order to promote the higher recovery of a carotenoid-rich PPF oil. The compositions of the mixtures composed of hydrocarbons (hexane, heptane, and cyclohexane) and short chain alcohols (ethanol and isopropanol) were defined from the calculation of the solute-solvent distance (Ra) between the solvent mixtures and the solute &beta;-carotene. The extraction experiments were conducted at 60 ± 2 °C during 5 hours in a batch extractor, using the hexane, heptane, cyclohexane, ethanol and isopropanol solvents and their mixtures, and at 55 ± 3 °C and a time interval of 1 hour and 30 minutes in a packed bed column using hexane, ethanol, isopropanol and their mixtures. The results of the batch extraction experiments at the solid: solvent mass ratio of 1:7 indicated that hexane and the mixture comprised of heptane and isopropanol extracted the highest lipid content, around 80 % (by mass), while that the other pure solvents and solvent mixtures allowed to obtain oil extraction yields around 70 % (by mass). Although the solvents cyclohexane and hexane had the highest extraction of carotenoids, the content of this component was slightly lower when the binary solvent mixtures were used. The higher yields of oil extraction of PPF in the column in the solid: solvent mass ratio of 1:4 were given by using ethanol and the mixture comprised of hexane and isopropanol, around 66 % (by mass), but the carotenoids content obtained was the same regardless of the solvent or solvent mixtures employed. The profile of carotenoids analyzed in UPLC/MS showed a high content of &beta;-carotene extracted mainly by hexane, while the highest content of &alpha;-carotene was obtained by the mixture of hexane and ethanol, finally, ethanol extracted the highest content of lycopene. In this dissertation, the synergism of extraction of PPF oil rich in carotenoids was not observed within the use of solvent mixtures defined from the estimation of Hansen Solubility Parameters (HSP) and calculation of Ra. However, it is possible to infer that the hydrocarbon solvents and their mixtures with the short-chain alcohols, ethanol, and isopropanol, demonstrated good ability to extract of PPF oil rich in carotenoids, maintaining its composition in fatty acids and free acidity constant being indicated for PPF oil extraction operations. The use of the solvent mixtures resulted in a considerable extraction yield of PPF oil, rich in total carotenoids showing that the partial replacement of hydrocarbon solvents by short chain alcohols is possible.

Dispersing co-crystals in a polymeric carrier may improve their physicochemical properties such as dissolution rate and solubility. Additionally co-crystal stability may be enhanced. However, such dispersions have been little investigated to date. This study focuses on the feasibility of dispersing co-crystals in a polymeric carrier and theoretical calculations to predict their stability. Acetone/chloroform, ethanol/water, and acetonitrile were used to load and grow co-crystals in a HPMCAS film. Caffeine-malonic acid and ibuprofennicotinamide co-crystals were prepared using solvent evaporation method. The interactions between each of the co-crystals components and their mixtures with the polymer were studied. A solvent evaporation approach was used to incorporate each compound, a mixture, and co-crystals into HPMCAS films. Differential scanning calorimetry data revealed a higher affinity of the polymer to acidic compounds than their basic counterparts as noticed by the depression of the glass transition temperature (Tg). Moreover, the same drug loading produced films with different Tgs when different solvents were used. Solubility parameter values (SP) of the solvents were employed to predict that effect on the depression of polymer Tg with relative success. SP values were more successful in predicting the preferential affinity of two acidic compounds to interact with the polymer. This was confirmed using binary mixtures of naproxen, flurbiprofen, malonic acid, and ibuprofen. On the other hand, dispersing basic compounds such as caffeine or nicotinamide with malonic acid in HPMCAS film revealed the growth of co-crystals. A dissolution study showed that the average release of caffeine from films containing caffeine-malonic acid was not significantly different to that of films containing similar caffeine concentration. The stability of the caffeine-malonic acid co-crystals in HPMC-AS was prolonged to 8 weeks at 95% relative humidity and 45°C. The theory developed in this project, that an acidic drug with a SP value closer to the polymer will dominate the interaction process and prevent the majority of the other material from interacting with the polymer, may have utility in designing co-crystal systems in polymeric vehicles

O uso do bagaço de cana-de-açúcar, um subproduto da produção sucroalcooleira, ainda está hoje atrelado diretamente à produção de energia com sua queima nas usinas, um uso que é pouco nobre, considerando-se a grande diversidade de compostos químicos presentes neste tipo de material. A possibilidade de valorização desta matéria-prima lignocelulósica está ligada a realização de etapas de separação das principais frações de compostos, a celulose, as hemiceluloses e a lignina. Neste contexto, as deslignificações organossolve, etapa de remoção da lignina através da solubilização da mesma em soluções orgânicas, tem grande potencial de uso, visto que nestas pode-se recuperar tanto a polpa como o licor de polpação para posterior uso. Assim, verifica-se que a solubilidade da lignina é o fator que diferencia a utilização de um dado solvente orgânico em uma deslignificação organossolve. Desta maneira, pode-se utilizar o conceito de parâmetros de solubilidade para a escolha de um melhor solvente para o processo. Neste trabalho, verificou-se a relação entre a deslignificação organossolve e a distância e afinidade de um solvente com a esfera de solubilidade de Hansen para a lignina de bagaço de cana-de-açúcar. Verificou-se que os parâmetros de solubilidade de Hansen para a lignina verificados na literatura não apresentam boa correlação com os dados de deslignificação, porém, uma nova esfera de solubilidade foi desenvolvida, na qual verificou-se um coeficiente de determinação de 0,93856, em detrimento de um de 0,72074 para a esfera de solubilidade verificada na literatura. Concluiu-se que o modelo desenvolvido possuía como principal diferença com relação ao modelo obtido por Hansen e Björkman para a lignina, um parâmetro de solubilidade para interações intermoleculares polares (&delta;p) inferior e um parâmetro de solubilidade para a capacidade de realização de ligações de hidrogênio (&delta;h) bem superior, porém mantendo o mesmo parâmetro de solubilidade total (&delta;). Confirmou-se a relação entre a deslignificação e os valores de distância e de afinidade obtidos neste trabalho, com a realização de deslignificações usando misturas ternárias e quaternárias com solventes de baixo custo e/ou excedentes no mercado (etanol, glicerol e 2-butanol, além de água). Concluiu-se que apesar da esfera de solubilidade desenvolvida permitir melhor ajuste dos dados, não se pode afirmar que esta é com certeza a esfera real para a lignina. / The use of sugarcane bagasse, a by-product of sugar and ethanol production, is still linked today directly to energy production with its burning in power plants, a use which is not very noble, considering the great diversity of chemical compounds present in the lignocellulosic matrix. The possibility of better use of lignocellulosic feedstock is linked to steps of separation of their main fractions, cellulose, hemicelluloses and lignin. In this context, organosolv delignification, in which lignin is removed by the solubilization in organic solutions have great potential, since both pulps and the pulping liquor can be recovered for later use. Thus, since the solubility of lignin is the factor that differentiates the use of a given organic solvent in an organosolv delignification, the concept of solubility parameters can be used for the selection of the organic solvent. In this dissertation the relationship between the distance and the affinity of a solvent with the Hansen sphere of solubility for lignin from bagasse cane sugar and organosolv delignification were studied. It was found that the Hansen solubility parameters for lignin found in the literature do not present a good correlation with delignification data. Thus a new sphere of solubility was developed, with a determination coefficient of 0.93856, over a determination coefficient of 0.72074 for the sphere of solubility found in the literature. It was concluded that the main differences between the developed model and the model obtained by Hansen and Björkman for lignin were a lower solubility parameter for polar intermolecular interactions (&delta;p) and a higher solubility parameter for hydrogen bonds (&delta;h), however keeping the same total solubility parameter (&delta;). The relationship between delignification and the values of the distance and affinity obtained in this work were confirmed with the attainment of organosolv delignification using tertiary and quaternary mixtures of solvents with low cost and/or availability in the market (ethanol, glycerol and 2-butanol, in addition to water). It was concluded that although the developed solubility sphere allowed a better fit of the data, it cannot be stated with certainty that this is the real sphere for lignin.