No description available.

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

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

The physicochemical properties of a drug affect to a large extent its subsequent biological absorption and bioavailability profile. Considerable pharmaceutical interest is therefore directed torwards the improvement of drug dissolution characteristics of drugs with low aqueous solubility. This thesis has considered the controlled modification of drug dissolution profiles by means of incorporating low concentrations of hydrophilic polymers by different processes into a host drug substance. In order to examine this approach and its potential use, the physicochemical, solid state, stability and tableting properties of a poorly aqueous soluble drug, phenylbutazone, in alternative polymorphic form and containing low levels of two hydrophilic polymers - hydroxypropyl methylcellulose (H.P.M.C.) and the surfactant poloxamer 188 - prepared by both conventional crystallisation and spray drying are reported. As an integral nart of the work attempts were mado to identify the different polymorphic forms of phenylbutazone. The δ-form, the commercially available stable form and the α and β metastable forms (nomenclature after Muller, 1978) were isolated. The α form was found to be unstable on storage. A 2 fold increase in intrinsic dissolution rate was observed for the metastable β-polymorph compared with the stable δ-polymorphic form. The effect of crystallisation rate on the formation of polymorphs of phenylbutazone was studied using a mini-spray dryer, and slower rates of crystallisation were found to favour polymorph formation. The hydrophilic polymers, H.P.M.C. and poloxamer 188, were incorporated by conventional crystallisation and spray drying into the drug crystal. Samples were subjected to a series of tests including differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, and intrinsic dissolution and solubility. When prepared by conventional crystallisation H.P.M.C. was found to form a "high energy" complex with phenylbutazone which melted 10°C lower than the parent drug. When prepared by spray drying H.P.M.C. inhibited the formation of the metastable β-polymorph of phenylbutazone. A 2 fold increase in intrinsic dissolution rate was observed for crystallised and spray dried samples containing 2% w/w or more added polymer. Poloxamer 188 did not form a complex with phenylbutazone and unlike H.P.M.C. did not inhibit the formation of the β-polymorph. For both crystallised and spray dried samples a 3 fold increase in dissolution rate was obtained at polymer levels of 1% w/w or above. The increase in dissolution has been attributed to facilitated wetting by lowering of interfacial tension rather than through the formation of micelles. The stability of selected phenylbutazone:polymer samples was tested at elevated temperatures. The stability was found to be affected both by the method of sample preparation and the type of additive. Large breakdowns occurring by a hydrolytic effect were identified for the crystallised phenylbutazone samples containing poloxamer 188. The effects on compaction of phenylbutazone in alternative form and presence of polymeric additives were studied by compressing samples of similar particle sizes of phenylbutazone as supplied (δ-form), samples of spray dried phenylbutazone (β-form) and samples containing different concentrations of H.P.M.C. prepared both by conventional crystallisation and spray drying. Compaction data were analysed according to the Heckel relationship and by force transmission ratio as well as from the tensile strengths of prepared tablets. The presence of H.P.M.C. up to 5% w/w concentration in phenylbutazone did not change the mean yield pressure for the crystallised or spray dried samples, although a difference in mean value was observed between the crystallised and spray dried materials, 93.22 MPa and 147.02 MPa respectively. Force transmission was found to be improved for samples containing H.P.M.C. prepared by both techniques and in general, the tablet tensile strengths for crystallised samples containing H.P.M.C. were approximately three times greater than for spray dried samples at equivalent tablet porosity. Differences are attributed to variation in solid state and particulate properties between samples.

The physicochemical properties of a drug affect to a large extent its subsequent biological absorption and bioavailability profile. Considerable pharmaceutical interest is therefore directed torwards the improvement of drug dissolution characteristics of drugs with low aqueous solubility. This thesis has considered the controlled modification of drug dissolution profiles by means of incorporating low concentrations of hydrophilic polymers by different processes into a host drug substance. In order to examine this approach and its potential use, the physicochemical, solid state, stability and tableting properties of a poorly aqueous soluble drug, phenylbutazone, in alternative polymorphic form and containing low levels of two hydrophilic polymers - hydroxypropyl methylcellulose (H. P. M. C. ) and the surfactant poloxamer 188 - prepared by both conventional crystallisation and spray drying are reported. As an integral nart of the work attempts were mado to identify the different polymorphic forms of phenylbutazone. The 6-form, the cammerdiallý 4- available stable ýorm and the a and s metastable forr. s (nomenclature after Huller, 1978).. were isolated. The a form was found to be unstable on storage. A .7 fold increase in intrinsic dissolution rate was observed for the metastable s-polymorph compared with the stable 6-polymorphic form. The effect of crystallisation rate on the formation of polymorphs of phenylbutazone was studied using a mini-spray dryer, and slower rates of crystallisation were found to favour polymorph formation. The hydrophilic polymers, H. P. M. C. and poloxamer 188 were incorporated by conventional crystallisation and spray drying into the drug crystal. Samples were subjected to a series of tests including differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, and intrinsic dissolution and solubility. When prepared by conventional crystallisation H. P. M. C. was f8und to form a "high energy" complex with phenylbutazone which melted 10 C lower than the parent drug. When prepared by spray drying H. P. M. C. inhibited the formation of the metastable a-polymorph of phenylbutazone. A2 fold increase in intrinsic dissolution rate was observed for crystallised and spray dried samples containing 2% w/w or more added polymer. Poloxamer 188 did not form a complex witý phenylbutazone and unlike H. P. M. C. did not inhibit thejgr gation of the a-polymorph. For both crystallised and spray fo0ld increase in dissolution rate was obtained at polymer levels oý 1% w/w or above. The increase in dissolution has been attributed to facilitated wetting by lowering of interfacial tension rather than through the formation of micelles. The stability of-selected phenylbutazone: polymer samples was tested at elevated temperatures. The stability was found to be affected both by the method of sample preparation and the type of additive. Large breakdowns occurring by a hydrolytic effect were identified for the crystallised phenylbutazone samples containing poloxamer 188. The effects on compact. ion of phenylbu. tazone in alternative form and presence of polymeric additives were studied by compressing samples of similar particle sizes of phenylbutazone as supplied (67form), samples of spray dried phenylbutazone (a-form) and samples containing different concentrations of H. P. M. C. prepared both by conventional crystallisation and spray drying. Compaction data were analysed according to the Heckel relationship and by force transmission ratio as well as from the tensile strengths of prepared tablets. The presence of H. P. M. C. up to 5% w/w concentration in phenylbutazone did not change the mean yield pressure for the crystallised or spray dried samples, although a difference in mean value was observed between the crystallised and spray dried materials, 93.22 MPa and 147.02 MPa respectively. Force transmission was found to be improved for samples containing H. P. M. C. prepared by both techniques and in general, the tablet tensile strengths for crystallised samples containing H. P. M. C. were approximately three times greater than for spray dried samples at equivalent tablet porosity. Differences are attributed to variation in solid state and particulate properties between samples. / Saudi Arabian Government

A película de amendoim é um resíduo da indústria de alimentos. Esse resíduo é rico em compostos fenólicos como resveratrol e procianidinas e apresenta elevada atividade antioxidante e atividade farmacológica. Apesar de suas atividades farmacológicas, compostos fenólicos apresentam baixa biodisponibilidade devido à glucuronidação catalisada pelas enzimas UDP-glucuronosyltransferases (UGTs), que acontece na primeira passagem no intestino e/ou fígado, dificultando a utilização dos compostos fenólicos como agentes terapêuticos. Filmes de desintegração oral permitem que o princípio ativo seja absorvido no epitélio bucal diretamente pela circulação sistêmica podendo melhorar a biodisponibilidade desses compostos naturais. Nesse contexto, o objetivo desse trabalho foi desenvolver um filme de desintegração oral à base de gelatina e hidroxipropilmetilcelulose (GEL:HPMC) incorporado com extrato de película de amendoim como um carreador de compostos bioativos. O extrato de película de amendoim foi produzido utilizando-se etanol (70%) como solvente (razão sólidos/solvente de 1:20) à temperatura ambiente sob agitação mecânica (10 minutos), sendo realizada três extrações consecutivas. O extrato foi liofilizado para ser caracterizado em relação à atividade antioxidante, fenólicos totais e aflatoxinas. Os filmes de desintegração oral com diferentes concentrações de gelatina e hidroxipropilmetilcelulose (GEL:HPMC) foram produzidos por casting (2g de macromoléculas/100 g de solução filmogênica e 0,4g de sorbitol/100g de solução filmogênica). O extrato de película de amendoim foi incorporado líquido e concentrado nas concentrações de 10, 20 e 30g/100g de solução filmogênica. Os filmes foram caracterizados em relação à propriedades mecânicas, ângulo de contato, tempo de desintegração, mucoadesividade, pH de superfície, microscopia eletrônica de varredura e espectroscopia de infravermelho. O extrato (liofilizado) apresentou concentração fenólica igual a 718,57 mg de equivalente em ácido gálico/g e EC50 igual a 146,07 ± 8.37 µg/mL e 0,37 ng B₁/g. Os filmes sem adição de extrato, independente da formulação, apresentaram homogeneidade e, de um modo geral, os filmes à base de hidroxipropilmetilcelulose apresentaram melhores propriedades mecânicas, hidrofilicidade superior, tempo de desintegração reduzido e mucoadesividade superior em relação aos filmes com gelatina em sua composição. Comportamento similar foi observado para os filmes de desintegração oral com adição de extrato. Entretanto, filmes com adição de extrato e altas concentrações de gelatina (100:0, 75:25) apresentaram formação de complexos insolúveis entre taninos e proteínas, aparentes visualmente. Em função dos resultados obtidos, os filmes à base de hidroxipropilmetilcelulose (0:100) e com 20% de extrato de película de amendoim apresentaram propriedades mecânicas superiores (tensão na ruptura = 26,63 MPa, elongação = 4,97% e módulo elástico = 1284,82 MPa) e menor tempo de desintegração (17,87 segundos) em relação as demais formulações, sendo esta considerada a formulação otimizada como potencial aplicação para filmes de desintegração oral. / Peanut skin is a food industry byproduct which is rich in phenolic compounds, such as resveratrol and procyanidins. Moreover, it has high antioxidant and pharmacological properties. Despite these activities, phenolic compounds have low oral bioavailability due to glucuronidation catalyzed by the enzyme UDP-glucuronosyltransferases (UGTs). This catalyze occurs in the first-pass metabolism (gut and/or liver) difficulting the use of phenolic compounds as therapeutic agents. For oral disintegrating films the active ingredient is directly absorbed into systemic circulation by oral epithelium improving the bioavailability of these natural compounds. The aim of this study was to develop oral disintegrating film composed of gelatin and hydroxypropyl methylcellulose (GEL: HPMC) added of peanut skin extract as a vehicle for bioactive compounds. The peanut skin extract was produced using ethanol (70%) as solvent (solid/solvent ratio 1:20) at room temperature under mechanical stirring (10 minutes) with three consecutive extractions. The extract was lyophilized to be characterized by antioxidant activity, total phenolic and aflatoxins. The oral disintegrating films were produced by casting (2g macromolecules/100 g filmogenic solution and 0.4g of sorbitol/100g of filmogenic solution) with different concentrations of gelatin and hydroxypropylmethylcellulose (GEL: HPMC). The peanut skin extract was added to films liquid and concentrated at concentrations of 10, 20 and 30g / 100g of filmogenic solution. The films were characterized by mechanical properties, contact angle, disintegrating time, mucoadesivity, surface pH, scanning electron microscopy and infrared spectroscopy. The extract (lyophilized) showed phenolic concentration of 718.57 mg of gallic acid equivalent/g, EC50 of 146.07 ± 8.37 µg/mL and 0.37 ng B₁/g. Films without extract, regardless of formulation were homogeneous. In general, hydroxypropyl methylcellulose films exhibited better mechanical properties, higher hydrophilicity and mucoadesivity and reduced disintegration time compared to films with gelatin in its composition. Similar behavior was observed for oral disintegrating films with addition of extract. Films formulation with high gelatin content (100: 0, 75:25) added of extract showed insoluble complexes formed between proteins and tannins. Hydroxypropyl methylcellulose films (0: 100) added of peanut skin extract (20%) showed superior mechanical properties (tensile strength = 26.63 MPa, elongation = 4.97% and elastic modulus = 1284.82 MPa) and lower disintegration time (17.87 seconds) compared with other formulations, which is considered the optimized formulation as a potential application for oral disintegrating films.

Arthrospira platensis ou Spirulina é uma microalga com alto valor nutricional. Foram preparados extratos de Spirulina, caracterizados e aplicados como estabilizadores de emulsão de óleo de girassol comercial em água (O/A) (10% v/v) na ausência e na presença de quatro tipos de hidroxipropil metilcelulose (HPMC). Os extratos brutos de Spirulina foram preparados em tampões a pH 6 (EB6) e pH 8 (EB8) por sonicação para promover a lise celular e a libertação de proteínas e fosfolípides; Parte dos extratos foi centrifugada (EC6 ou EC8). Independentemente das condições de extração, todos os extratos apresentados apresentaram valores de potencial-&#950 médio variando de - (16 ± 2) mV a - (20 ± 2) mV, tamanho médio variando de (108 ± 52) nm a (306 ± 68) nm e atividade interfacial. As emulsões O/A preparadas com extratos de Spirulina (10 g / L) exibiram partículas com potencial- médio variando de - (16 ± 2) mV a - (27 ± 4) mV, tamanho médio variando de ~ 70 nm (EB6 ou EB8) a ~ 700 nm (EC6 ou EC8). No entanto, o EB6 levou a emulsões ligeiramente mais estáveis do que as outras. A combinação de EB6 (10 g / L) e HPMC (1,0 % m/m) levou a um aumento substancial na estabilidade da emulsão, embora os valores de potencial- diminuíram uma ordem de grandeza. Em particular, a HPMC com a maior massa molar e o maior grau de substituição de grupos metila conduziu a i) camada interfacial mais robusta resultante da formação de complexos entre cadeias HPMC e proteínas EB6 e (ii) meio contínuo mais viscoso. / Arthrospira platensis or Spirulina is a microalga with a high nutritional value. Extracts of Spirulina were prepared, characterized and applied as oil in water (O/W) (10 % v/v) emulsion stabilizers in the absence and presence of four types of hydroxypropyl methylcellulose (HPMC). The emulsions were prepared with edible sunflower oil. Crude extracts of Spirulina were prepared in buffers at pH 6 (CE6-Crude extract pH6) and pH 8 (CE8-Crude extract pH8) by sonication to promote cell lysis and protein and phospholipids release; part of the extracts was centrifuged (CCE6 or CCE8). Regardless of the extraction conditions, all extracts presented mean -potential ranging from (16 ± 2) mV to (20 ± 2) mV, mean diameter ranging from (108 ± 52) nm to (306 ± 68) nm and interfacial activity. The emulsions prepared with Spirulina extracts (10 g/L) displayed particles with mean -potential ranging from (16 ± 2) mV to (27 ± 4) mV, mean diameter ranging from ~ 70 nm (CCE6 or CCE8) to ~ 700 nm (CE6 or CE8). However, CE6 led to emulsions slightly more stable than the others did. The combination of CE6 (10 g/L) HPMC (1.0 wt %) led to substantial increase in the emulsion stability, although the -potential values decreased one order of magnitude. Particularly, the HPMC with the highest molecular weight and highest methyl substitution degree led to the most (i) robust interfacial layer resulting from the complex formation between HPMC chains and CE6 proteins and (ii) viscous continuous medium.

Arthrospira platensis ou Spirulina é uma microalga com alto valor nutricional. Foram preparados extratos de Spirulina, caracterizados e aplicados como estabilizadores de emulsão de óleo de girassol comercial em água (O/A) (10% v/v) na ausência e na presença de quatro tipos de hidroxipropil metilcelulose (HPMC). Os extratos brutos de Spirulina foram preparados em tampões a pH 6 (EB6) e pH 8 (EB8) por sonicação para promover a lise celular e a libertação de proteínas e fosfolípides; Parte dos extratos foi centrifugada (EC6 ou EC8). Independentemente das condições de extração, todos os extratos apresentados apresentaram valores de potencial-&#950 médio variando de - (16 ± 2) mV a - (20 ± 2) mV, tamanho médio variando de (108 ± 52) nm a (306 ± 68) nm e atividade interfacial. As emulsões O/A preparadas com extratos de Spirulina (10 g / L) exibiram partículas com potencial- médio variando de - (16 ± 2) mV a - (27 ± 4) mV, tamanho médio variando de ~ 70 nm (EB6 ou EB8) a ~ 700 nm (EC6 ou EC8). No entanto, o EB6 levou a emulsões ligeiramente mais estáveis do que as outras. A combinação de EB6 (10 g / L) e HPMC (1,0 % m/m) levou a um aumento substancial na estabilidade da emulsão, embora os valores de potencial- diminuíram uma ordem de grandeza. Em particular, a HPMC com a maior massa molar e o maior grau de substituição de grupos metila conduziu a i) camada interfacial mais robusta resultante da formação de complexos entre cadeias HPMC e proteínas EB6 e (ii) meio contínuo mais viscoso. / Arthrospira platensis or Spirulina is a microalga with a high nutritional value. Extracts of Spirulina were prepared, characterized and applied as oil in water (O/W) (10 % v/v) emulsion stabilizers in the absence and presence of four types of hydroxypropyl methylcellulose (HPMC). The emulsions were prepared with edible sunflower oil. Crude extracts of Spirulina were prepared in buffers at pH 6 (CE6-Crude extract pH6) and pH 8 (CE8-Crude extract pH8) by sonication to promote cell lysis and protein and phospholipids release; part of the extracts was centrifuged (CCE6 or CCE8). Regardless of the extraction conditions, all extracts presented mean -potential ranging from (16 ± 2) mV to (20 ± 2) mV, mean diameter ranging from (108 ± 52) nm to (306 ± 68) nm and interfacial activity. The emulsions prepared with Spirulina extracts (10 g/L) displayed particles with mean -potential ranging from (16 ± 2) mV to (27 ± 4) mV, mean diameter ranging from ~ 70 nm (CCE6 or CCE8) to ~ 700 nm (CE6 or CE8). However, CE6 led to emulsions slightly more stable than the others did. The combination of CE6 (10 g/L) HPMC (1.0 wt %) led to substantial increase in the emulsion stability, although the -potential values decreased one order of magnitude. Particularly, the HPMC with the highest molecular weight and highest methyl substitution degree led to the most (i) robust interfacial layer resulting from the complex formation between HPMC chains and CE6 proteins and (ii) viscous continuous medium.

A película de amendoim é um resíduo da indústria de alimentos. Esse resíduo é rico em compostos fenólicos como resveratrol e procianidinas e apresenta elevada atividade antioxidante e atividade farmacológica. Apesar de suas atividades farmacológicas, compostos fenólicos apresentam baixa biodisponibilidade devido à glucuronidação catalisada pelas enzimas UDP-glucuronosyltransferases (UGTs), que acontece na primeira passagem no intestino e/ou fígado, dificultando a utilização dos compostos fenólicos como agentes terapêuticos. Filmes de desintegração oral permitem que o princípio ativo seja absorvido no epitélio bucal diretamente pela circulação sistêmica podendo melhorar a biodisponibilidade desses compostos naturais. Nesse contexto, o objetivo desse trabalho foi desenvolver um filme de desintegração oral à base de gelatina e hidroxipropilmetilcelulose (GEL:HPMC) incorporado com extrato de película de amendoim como um carreador de compostos bioativos. O extrato de película de amendoim foi produzido utilizando-se etanol (70%) como solvente (razão sólidos/solvente de 1:20) à temperatura ambiente sob agitação mecânica (10 minutos), sendo realizada três extrações consecutivas. O extrato foi liofilizado para ser caracterizado em relação à atividade antioxidante, fenólicos totais e aflatoxinas. Os filmes de desintegração oral com diferentes concentrações de gelatina e hidroxipropilmetilcelulose (GEL:HPMC) foram produzidos por casting (2g de macromoléculas/100 g de solução filmogênica e 0,4g de sorbitol/100g de solução filmogênica). O extrato de película de amendoim foi incorporado líquido e concentrado nas concentrações de 10, 20 e 30g/100g de solução filmogênica. Os filmes foram caracterizados em relação à propriedades mecânicas, ângulo de contato, tempo de desintegração, mucoadesividade, pH de superfície, microscopia eletrônica de varredura e espectroscopia de infravermelho. O extrato (liofilizado) apresentou concentração fenólica igual a 718,57 mg de equivalente em ácido gálico/g e EC50 igual a 146,07 ± 8.37 µg/mL e 0,37 ng B₁/g. Os filmes sem adição de extrato, independente da formulação, apresentaram homogeneidade e, de um modo geral, os filmes à base de hidroxipropilmetilcelulose apresentaram melhores propriedades mecânicas, hidrofilicidade superior, tempo de desintegração reduzido e mucoadesividade superior em relação aos filmes com gelatina em sua composição. Comportamento similar foi observado para os filmes de desintegração oral com adição de extrato. Entretanto, filmes com adição de extrato e altas concentrações de gelatina (100:0, 75:25) apresentaram formação de complexos insolúveis entre taninos e proteínas, aparentes visualmente. Em função dos resultados obtidos, os filmes à base de hidroxipropilmetilcelulose (0:100) e com 20% de extrato de película de amendoim apresentaram propriedades mecânicas superiores (tensão na ruptura = 26,63 MPa, elongação = 4,97% e módulo elástico = 1284,82 MPa) e menor tempo de desintegração (17,87 segundos) em relação as demais formulações, sendo esta considerada a formulação otimizada como potencial aplicação para filmes de desintegração oral. / Peanut skin is a food industry byproduct which is rich in phenolic compounds, such as resveratrol and procyanidins. Moreover, it has high antioxidant and pharmacological properties. Despite these activities, phenolic compounds have low oral bioavailability due to glucuronidation catalyzed by the enzyme UDP-glucuronosyltransferases (UGTs). This catalyze occurs in the first-pass metabolism (gut and/or liver) difficulting the use of phenolic compounds as therapeutic agents. For oral disintegrating films the active ingredient is directly absorbed into systemic circulation by oral epithelium improving the bioavailability of these natural compounds. The aim of this study was to develop oral disintegrating film composed of gelatin and hydroxypropyl methylcellulose (GEL: HPMC) added of peanut skin extract as a vehicle for bioactive compounds. The peanut skin extract was produced using ethanol (70%) as solvent (solid/solvent ratio 1:20) at room temperature under mechanical stirring (10 minutes) with three consecutive extractions. The extract was lyophilized to be characterized by antioxidant activity, total phenolic and aflatoxins. The oral disintegrating films were produced by casting (2g macromolecules/100 g filmogenic solution and 0.4g of sorbitol/100g of filmogenic solution) with different concentrations of gelatin and hydroxypropylmethylcellulose (GEL: HPMC). The peanut skin extract was added to films liquid and concentrated at concentrations of 10, 20 and 30g / 100g of filmogenic solution. The films were characterized by mechanical properties, contact angle, disintegrating time, mucoadesivity, surface pH, scanning electron microscopy and infrared spectroscopy. The extract (lyophilized) showed phenolic concentration of 718.57 mg of gallic acid equivalent/g, EC50 of 146.07 ± 8.37 µg/mL and 0.37 ng B₁/g. Films without extract, regardless of formulation were homogeneous. In general, hydroxypropyl methylcellulose films exhibited better mechanical properties, higher hydrophilicity and mucoadesivity and reduced disintegration time compared to films with gelatin in its composition. Similar behavior was observed for oral disintegrating films with addition of extract. Films formulation with high gelatin content (100: 0, 75:25) added of extract showed insoluble complexes formed between proteins and tannins. Hydroxypropyl methylcellulose films (0: 100) added of peanut skin extract (20%) showed superior mechanical properties (tensile strength = 26.63 MPa, elongation = 4.97% and elastic modulus = 1284.82 MPa) and lower disintegration time (17.87 seconds) compared with other formulations, which is considered the optimized formulation as a potential application for oral disintegrating films.

No presente trabalho foi realizado o isolamento da 3-O-metilquercetina, a partir de produto seco do extrato de inflorescências de Achyrocline satureioides, e sua caracterização. Em etapa farmacotécnica, foi realizado o estudo da associação deste flavonóide com b-ciclodextrina, bem como testes preliminares de permeação cutânea das associações, incorporadas ou não em gel de hidroxipropilmetilcelulose. As técnicas espectroscópicas, infravermelho e ressonância magnética de hidrogênio, confirmaram a estrutura do flavonóide isolado. Para o doseamento da 3-Ometilquercetina, realizou-se a validação de metodologia analítica por cromatografia líquida de alta eficiência, obtendo-se linearidade, na faixa de concentração de 0,05 a 1,5 μg/mL, precisão e exatidão adequadas. A análise da associação da 3-Ometilquercetina com b-ciclodextrina por infravermelho, ressonância magnética de hidrogênio e a análise pelo método empírico de Mecânica Molecular (MM2) do software Chem3D Ultra (Versão 9.0, CambridgeSoft) indicam possível inclusão do anel B da 3-O-metilquercetina na cavidade da b-ciclodextrina, sendo a inserção do flavonóide pela borda das hidroxilas secundárias mais favorável do que pela borda das hidroxilas primárias. A b-ciclodextrina e o gel de hidroxipropilmetilcelulose promoveram a permeação do flavonóide através da pele. A realização de ensaios in vivo para a seleção da melhor formulação constitui-se na principal perspectiva de continuidade de investigação científica do tema. / 3-O-methylquercetin (3-OMQ) was isolated from spray dried powder of Achyrocline satureioides and characterized by IR and 1H NMR. The study of association of this flavonoid with b-cyclodextrin (bCD) was performed, as well as preliminary skin permeation tests of these associations, incorporated or not in hydroxypropyl methylcellulose (HPMC) hydrogel. A LC method for 3-OMQ assay was validated in the concentration range from 0.05 to 1.5 μg/mL, with suitable precision and accuracy. The complexation of 3-OMQ with bCD was analyzed by IR, 1H NMR and Molecular Mechanics (Chem3D Ultra 9.0, CambridgeSoft) and the results indicated the possible insertion of B ring of the flavonoid into the bCD cavity, being the insertion through the secondary OH rim more favorable than through the primary OH rim. bCD and HPMC promoted the permeation of the flavonoid through the skin. In vivo assay is required to select the appropriate formulation.