Poly(N-isopropylacrylamide)-co-acrylamide hydrogels for the controlled release of bromelain from agroindustrial residues of Ananas comosus

This works reports the purification of bromelain extracted from Ananas comosus industrial residues by ethanol purification, its partial characterization from the crude extract as well as the ethanol purified enzyme, and its application onto poly(N-isopropylacrylamide)-co-acrylamide hydrogels. Bromelain was recovered within the 30–70 % ethanol fraction, which achieved a purification factor of 3.12-fold, and yielded more than 90 % of its initial activity. The resulting purified bromelain contained more than 360 U · mg−1, with a maximum working temperature of 60 °C and pH of 8.0. Poly(N-isopropylacrylamide)-co-acrylamide hydrogels presented a swelling rate of 125 %, which was capable of loading 56 % of bromelain from the solution, and was able to release up to 91 % of the retained bromelain. Ethanol precipitation is suitable for bromelain recovery and application onto poly(N-isopropylacrylamide)-co-acrylamide hydrogels based on its processing time and the applied ethanol prices8117191726CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAIS - FAPEMIGsem informaçã

Poly(n-isopropylacrylamide)-co-acrylamide Hydrogels For The Controlled Release Of Bromelain From Agroindustrial Residues Of Ananas Comosus.

This works reports the purification of bromelain extracted from Ananas comosus industrial residues by ethanol purification, its partial characterization from the crude extract as well as the ethanol purified enzyme, and its application onto poly(N-isopropylacrylamide)-co-acrylamide hydrogels. Bromelain was recovered within the 30-70 % ethanol fraction, which achieved a purification factor of 3.12-fold, and yielded more than 90 % of its initial activity. The resulting purified bromelain contained more than 360 U · mg(-1), with a maximum working temperature of 60 °C and pH of 8.0. Poly(N-isopropylacrylamide)-co-acrylamide hydrogels presented a swelling rate of 125 %, which was capable of loading 56 % of bromelain from the solution, and was able to release up to 91 % of the retained bromelain. Ethanol precipitation is suitable for bromelain recovery and application onto poly(N-isopropylacrylamide)-co-acrylamide hydrogels based on its processing time and the applied ethanol prices.811719-172

Hipopara-Red, Real Life Experience in 322 Patients with Hypoparathyroidism

Context:Hypoparathyroidism is a rare disease and as such, its natural history, long term complications and correct clinical management remain unclear.ObjectiveTo describe the natural history and clinical characteristics of the disease.Design and settingTopresent a retrospective observational analysis from seven specialized centers in Buenos Aires, Argentina.Patientschronic hypoparathyroid patients followed up between 1985 and December 2018.Main Outcome Measuresdata on demographics, etiology, clinical complications, biochemical parameters, DXA values and treatment doses were collected.Results322 subjects with chronic hypoparathyroidism were included, 85.7 % were female. Mean age was 55.2 ± 16.8 years and mean age at diagnosis was 43.8 ± 16.8. Prevalence of surgical hypoparathyroidism was 90.7 %, most common causes being thyroid carcinoma and benign thyroid disease. A history of hypocalcemia requiring hospitalization was present in 25.7 % and 4.3 % had a history of seizures. Overall, 40.9 % had reported at least one neuromuscular symptom. Renal insufficiency was present in 22.4 % and was significantly associated with age (p<0.0001). Hyperphosphatemia was present in 42 %. A history of severe hypocalcemia, paresthesias, tetany, ganglia calcifications, seizures and cataracts was significantly higher in nonsurgical patients.ConclusionAlthough these patients were followed up by experienced physicians, clinical management was heterogeneous and probably insufficient to assess all the potential complications of this chronic disease. Almost 70 % of this group of patients met the experts´ indications for considering the use of rhPTH 1-84. Being aware of this fact is the first step to improve our medical management of this disease in the future.Fil: Zanchetta, María Belén. Universidad del Salvador; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Robbiani, Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Universidad del Salvador; ArgentinaFil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Giacoia, Evangelina. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Frigeri, Adriana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Dr. Teodoro Álvarez"; ArgentinaFil: Kallsbrum, Silvia. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; ArgentinaFil: Salerni, Helena. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; ArgentinaFil: Lucas, Sabrina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; ArgentinaFil: Diaz, Adriana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; ArgentinaFil: Perez, Betiana. Hospital Italiano; ArgentinaFil: Pieroni, Luisina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Dr. Teodoro Álvarez"; ArgentinaFil: Arce Lange, María Auxiliadora. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Dr. Teodoro Álvarez"; ArgentinaFil: Tormo, Silvina. Hospital Nacional Profesor Alejandro Posadas.; ArgentinaFil: Kitaigrodsky, Ariela. Hospital Italiano; ArgentinaFil: Galich, Ana María. Hospital Italiano; Argentin

Reference Values of Three-Dimensional Proximal Femur Parameters from Bone Densitometry Images in Healthy Subjects from Argentina

Objective: New methodologies for the assessment of bone mass from by DXA have been developed in the last years. The threedimensional analysis of the proximal femur by (3D-DXA) allows the evaluation of cortical and trabecular bone separately and has shown a good correlation with computed tomography. We aimed to obtain reference values in a healthy population of both sexesin Argentina.Methods: Adults female and male subjects (n=992) from four cities from Argentina were included. BMD (g/cm2) was measured by DXA on the femoral neck and total hip. The 3D analysis was performed with 3D-Shaper software (v2.9, Galgo Medical, Spain).The cortical BMD (sDens - mg/cm2) and trabecular volumetric BMD (trab vBMD - mg/cm3) were consider. The distribution of the data was evaluated with the Shapiro-Wilk test and parametricor non-parametric tests were used as appropriate. Data were expressed as mean±SD and p<0.05 was considered significant.Results: 75.5% women (n=749) and 24.5% men (n=243) were included. The mean age was 54.8±16.8 y and BMI was 27.3±5.4 kg/m2. The data according to each decade and a comparison with a references group (decade 20-30) are shown in the following table (*indicates significant differences compared to decade 20-30).Conclusion: A significant decrease in trabecular vBMD from D40 was observed in women, while in men this decrease was observed later (D60). The cortical parameter sDens was observed decreasefrom D50 in women and in men, an increase in D40 and cortical bone maintenance according to age was found.Fil: Brance, M. L.. Reumatología y Enfermedades Óseas; ArgentinaFil: Saravi, Fernando Daniel. Escuela de Medicina Nuclear; ArgentinaFil: Henríquez, M. M.. Escuela de Medicina Nuclear; ArgentinaFil: Longobardi, V.. Instituto de Investigaciones Metabólicas; ArgentinaFil: Zanchetta, M. B.. Instituto de Investigaciones Metabólicas; ArgentinaFil: Larroudé, M. S.. Centro de Diagnostico Rossi; ArgentinaFil: Ulla, M. R.. Instituto Latinoamericano de Investigaciones Médicas; ArgentinaFil: Matos, F.. Instituto Latinoamericano de Investigaciones Médicas; ArgentinaFil: Salerni, H.. No especifíca;Fil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Bonanno, Marina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Meneses, N. L.. No especifíca;Fil: Di Gregorio, S.. Fundacion Cetir.; EspañaFil: Brum, L. R.. Universidad Nacional de Rosario; ArgentinaWorld Congress on Osteoporosis, Osteoarthritis and Musculoskeletal DiseasesVirtualBélgicaInternational Osteoporosis FoundationEuropean Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Disease

Densitometric Response in Postmenopausal Osteoporosis Treated with Strontium Ranelate or Denosumab

Tanto el ranelato de estroncio (RSr) como el denosumab (Dmab) son eficaces en el tratamiento de la osteoporosis (OP) posmenopáusica (PM). El efecto de cada fármaco por separado sobre la densidad mineral ósea (DMO) ha sido estudiado recientemente. Con ambas drogas se observó, al año de tratamiento, un aumento significativo de la DMO en columna lumbar (CL), cuello femoral (CF) y cadera total (CT). En este trabajo comparamos la respuesta densitométrica al año de tratamiento con una y otra droga. Utilizamos los registros de 425 pacientes PMOP tratadas con Dmab y 441 tratadas con RSr. En cada paciente analizamos el porcentaje de cambio; se clasificaron como respondedoras aquellas que mostraron un cambio ≥3%. Adicionalmente se comparó la respuesta en pacientes no previamente tratadas con bifosfonatos (BF-naïve) en comparación con pacientes que habían recibido previamente un BF. Al analizar el grupo completo para Dmab, el porcentaje de pacientes respondedoras fue de 68,4% en CL, 63,3% en CF y 49,3% en CT. Por otro lado, en el grupo de pacientes tratadas con RSr, el porcentaje de respondedoras (53,8% en CL, 40,0% en CF y 35,6% en CT) fue estadísticamente menor. Cuando comparamos la respuesta entre las pacientes BF-naïve que recibieron RSr o Dmab, el Dmab indujo mayor respuesta en CL y CF que el grupo RSr, sin diferencias en CT. Cuando se analizaron los subgrupos BF-previo, las tratadas con Dmab mostraron mayor respuesta en todas las regiones. Conclusión: en pacientes con OP-PM, el tratamiento con Dmab produjo mayores incrementos densitométricos que el RSr, siendo el porcentaje de pacientes respondedoras mayor con Dmab que con RSr.Both strontium ranelate (SrR) and denosumab (Dmab) are effective in the treatment of postmenopausal osteoporosis (PMOP). The effect of each drug on bone mineral density (BMD) has been studied separately by us. With both treatments, there was a significant increase after one year of treatment at the lumbar spine (LS) and hip. In this paper we compared the densitometric response after one year of treatment with both drugs used separately. We used the clinical records of 425 PM patients treated with Dmab and 441 treated with SrR. For each patient we analyzed the percentage of change; those who showed a change ≥3% were classified as responders. Additionally, the response was compared in patients not previously treated with bisphosphonates (BP-naïve) compared to patients who had previously received a BP. When analyzing the complete group for Dmab, the percentage of “responders” was 65.2% at the LS, 62.9% at the femoral neck (FN) and 47.4% at the total hip (TH). On the other hand, in the group of patients treated with SrR the percentage of responders (53.8% at the LS, 40.0% at the FN and 35.6% at the TH) was statistically lower. When comparing the response between in BF-naïve patients receiving RSr or Dmab, Dmab induced a greater response at the LS and FN than the RSr group, with no statistical differences at the TH. When the subgroups with prior BP treatment were analyzed, those treated with Dmab showed greater response in all regions. Conclusion: in patients with PMOP treatment with Dmab produced greater densitometric increments than SrR, and the percentage of responders was higher with Dmab than with SrR.Facultad de Ciencias Médica

Densitometric response in postmenopausal osteoporosis treated with strontium ranelate or denosumab

Tanto el ranelato de estroncio (RSr) como el denosumab (Dmab) son eficaces en el tratamiento de la osteoporosis (OP) posmenopáusica (PM). El efecto de cada fármaco por separado sobre la densidad mineral ósea (DMO) ha sido estudiado recientemente. Con ambas drogas se observó, al año de tratamiento, un aumento significativo de la DMO en columna lumbar (CL), cuello femoral (CF) y cadera total (CT). En este trabajo comparamos la respuesta densitométrica al año de tratamiento con una y otra droga. Utilizamos los registros de 425 pacientes PMOP tratadas con Dmab y 441 tratadas con RSr. En cada paciente analizamos el porcentaje de cambio; se clasificaron como respondedoras aquellas que mostraron un cambio ≥3%. Adicionalmente se comparó la respuesta en pacientes no previamente tratadas con bifosfonatos (BF-naïve) en comparación con pacientes que habían recibido previamente un BF. Al analizar el grupo completo para Dmab, el porcentaje de pacientes respondedoras fue de 68,4% en CL, 63,3% en CF y 49,3% en CT. Por otro lado, en el grupo de pacientes tratadas con RSr, el porcentaje de respondedoras (53,8% en CL, 40,0% en CF y 35,6% en CT) fue estadísticamente menor. Cuando comparamos la respuesta entre las pacientes BF-naïve que recibieron RSr o Dmab, el Dmab indujo mayor respuesta en CL y CF que el grupo RSr, sin diferencias en CT. Cuando se analizaron los subgrupos BF-previo, las tratadas con Dmab mostraron mayor respuesta en todas las regiones. Conclusión: en pacientes con OP-PM, el tratamiento con Dmab produjo mayores incrementos densitométricos que el RSr, siendo el porcentaje de pacientes respondedoras mayor con Dmab que con RSr.Both strontium ranelate (SrR) and denosumab (Dmab) are effective in the treatment of postmenopausal osteoporosis (PMOP). The effect of each drug on bone mineral density (BMD) has been studied separately by us. With both treatments, there was a significant increase after one year of treatment at the lumbar spine (LS) and hip. In this paper we compared the densitometric response after one year of treatment with both drugs used separately. We used the clinical records of 425 PM patients treated with Dmab and 441 treated with SrR. For each patient we analyzed the percentage of change; those who showed a change ≥3% were classified asresponders. Additionally, the response was compared in patients not previously treated with bisphosphonates (BP-naïve) compared to patients who had previously received a BP. When analyzing the complete group for Dmab, the percentage of “responders” was 65.2% at the LS, 62.9% at the femoral neck (FN) and 47.4% at the total hip (TH). On the other hand, in the group of patients treated with SrR the percentage of responders (53.8% at the LS, 40.0% at the FN and 35.6% at the TH) was statistically lower. When comparing the response between in BF-naïve patients receiving RSr or Dmab, Dmab induced a greater response at the LS and FN than the RSr group, with no statistical differences at the TH. When the subgroups with prior BP treatment were analyzed, those treated with Dmab showed greater response in all regions. Conclusion: in patients with PMOP treatment with Dmab produced greater densitometric increments than SrR, and the percentage of responnders was higher with Dmab than with SrR.Fil: Sánchez, Ariel. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro de Endocrinología SRL; ArgentinaFil: Brun, Lucas Ricardo Martín. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario; ArgentinaFil: Salerni, Helena. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo; ArgentinaFil: Costanzo Caso, Pablo Alejandro. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo; ArgentinaFil: Maffei, Ana Laura. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios Asociados de Endocrinología Dra. Laura Maffei; ArgentinaFil: Pemrou, Valeria. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios Asociados de Endocrinología Dra. Laura Maffei; ArgentinaFil: Sarli, Marcelo A.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Rey, Paula. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Larraoudé, María Silvia. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Hospital Milstein; ArgentinaFil: Brance, María Lorena. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Ósea; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Galich, Ana María. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Servicio de Endocrinología del Hospital Italiano de Buenos Aires; ArgentinaFil: Gonzalez, Diana. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Mautalen Salud e Investigación; ArgentinaFil: Bagur, Alicia Cristina. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Mautalen Salud e Investigación; ArgentinaFil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Grupo Argentino de Estudio de la Osteoporosis; ArgentinaFil: Vega, Eduardo. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Cesan; Argentina. Instituto de la Mujer; ArgentinaFil: Zanchetta, María B.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Farias, Vanina. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Manzur, José L.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro de Endocrinología y Osteoporosis; ArgentinaFil: Moggia, María S.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro Tiempo; ArgentinaFil: Ulla, María R.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro de Endocrinología y Osteopatías Médicas; ArgentinaFil: Pavlove, María M.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Agudos Carlos Durand.; ArgentinaFil: Karlsbrum, Silvia. Hospital Durand; Argentina. Grupo Argentino de Estudio de la Osteoporosis; ArgentinaFil: Grupo Argentino de Estudio de la Osteoporosis. No especifíca

Liposomal nanoestruturated system containing chalcone CH8 for the cutaneous leishmaniasis treatment

Orientador: Maria Helena Andrade SantanaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia QuimicaResumo: Atualmente, os lipossomas elásticos têm se destacado em relação aos lipossomas convencionais (LC), pela capacidade de atingir as camadas mais profundas da pele. Neste trabalho, lipossomas elásticos foram preparados e caracterizados quanto às suas propriedades físico-químicas, de permeação in vitro e ex vivo, e aplicados ao tratamento tópico da leishmaniose cutânea. Estes lipossomas foram compostos de lecitina de ovo, e tiveram a sua superfície modificada pela incorporação do tensoativo PEG:8L, formando os lipossomas peguilados (LP). O fármaco encapsulado foi uma chálcona sintética nitrogenada (CH8), que vem se destacando como substância antiprotozoária e apresenta dificuldade de permeação através da pele. Os resultados obtidos mostram que o PEG-8L é incorporado na bicamada lipídica dos LC, produzindo maior fluidez e elasticidade. A incorporação do PEG-8L também modifica a tensão superficial e o potencial zeta dos LC. A encapsulação da CH8 foi verificada em ambos os casos (LC e LP), com modificações na morfologia, diâmetro médio, tensão superficial e temperatura de transição de fase em relação aos LC vazios. Os estudos de permeação em membranas sintéticas de nanoporos (in vitro) mostraram que os LP possuem maior capacidade de permeação que os LC, e que a CH8 produz elasticidade aos LC aumentando sua capacidade de permeação em relação aos LP contendo CH8. Os estudos de permeação em pele de orelha de porco (ex vivo) mostraram que a CH8, em ambos os tipos de lipossomas, foi capaz de permear as camadas da pele e atingir a derme. Os resultados in vivo no tratamento da leishmaniose em camundongos mostraram que as formulações lipossomais foram mais eficientes que a CH8 livre, destacando-se a eficácia da CH8 em LC, cuja ação foi semelhante à aplicação da CH8 livre intralesional. Os resultados obtidos mostram o desenvolvimento tecnológico da preparação de LC e LP contendo CH8, e contribuem para o tratamento mais eficaz da leishmaniose cutânea.Abstract: Nowadays, elastic liposome (EL), has gained attention when compared with conventional liposome (CL), by its capacity of reach the skin's deepest layers. In this work, elastic liposome were prepared and characterized by its physic-chemical properties, in vivo and ex vivo permeation, and its application for cutaneous leishimania topical treatment. The liposome was composed by egg lecithin, and had it surface modified by the incorporation of PEG-8L tensoactive, forming PEGylated liposome (PL). The encapsulated drug was a synthetic nitrogened chalcone (CH8), which has aroused as anti-protozoa substance and presents difficult permeation through the skin. Results obtained shows that PEG-8L was incorporated on LC's lipid bilayer, producing enhanced elasticity and fluidity. PEG- 8L incorporation also modifies the superficial tension and zeta's potencial of the CL. CH8's encapsulation was observed in both cases, presenting modification at morphology, mean diameter, superficial tension and phase transition's temperature when related with empty CL. The permeation studies in synthetic nanopores' membranes (in vitro) showed that PL has higher permeation capacity than CLf and CH8 produced some elasticity to CL increasing its permeation capacity even when related to PL containing CH8. The pig's ear skin permeation studies (ex vivo) showed that CH8 in both liposome types was capable of permeate the skin layers, reaching the dermis. Mice leishimania treatment in vivo results showed that the liposomal formulation was more efficient that free CH8, underling CH8's efficiency in CL, in which the action was similar to free CH8 intra-wound application. Results showed the technological development of CL and PL containing CH8 that contribute to a more efficiency treatment of coetaneous leishmania.MestradoDesenvolvimento de Processos BiotecnologicosMestre em Engenharia Químic

Self-emulsifying drug delivery system : development, characterization and applications

Orientador: Maria Helena Andrade SantanaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia QuímicaResumo: Sistemas Auto-Emulsionáveis para Liberação Modificada de Fármacos (SEDDS) possuem potencial para melhorar a biodisponibilidade de fármacos pouco solúveis em água. Após a administração por via oral, estes sistemas dispersam-se rapidamente no fluido gástrico, resultando em micro/nanoemulsões contendo o fármaco solubilizado. O desenvolvimento de formulações SEDDS depende da avaliação da solubilidade do fármaco em diferentes veículos, da compatibilidade do ativo com os excipientes, da capacidade de auto-emulsificação e do delineamento da região auto-emulsionável. Desta forma, a solubilidade de um fármaco modelo (L294) foi avaliada em vários veículos não aquosos, que incluem óleos, tensoativos e co-tensoativos; a sua compatibilidade foi determinada para os excipientes mais promissores; e o diagrama de fases ternário foi construído para identificar a região auto-emulsionável. Ensaios in vitro (tamanho de partículas, índice de polidispersibilidade, potencial zeta e turbidez) foram realizados para caracterizar o desempenho das formulações. A partir dos resultados preliminares, o óleo Labrafac PG, o tensoativo Labrasol e o co-tensoativo Transcutol HP demonstraram ser os mais promissores para a construção do SEDDS, e seu diagrama de fases resultou em oito formulações auto-emulsionáveis, contendo diferentes composições, as quais apresentaram tamanho de partículas em torno de 100 ± 10 nm. Assim, os componentes das formulações SEDDS (Labrafac PG, Labrasol e Transcutol HP) foram selecionados com o intuito de melhorar a biodisponibilidade oral do L294Abstract: Self-Emulsifying Drug Delivery Systems (SEDDS) have the potential to improve bioavailability of poorly water-soluble drugs. After oral administration, these systems disperse rapidly on the gastric fluid, resulting in micro/nano-emulsions containing the solubilized drug. The development of SEDDS formulations depend on the drug solubility evaluation in different vehicles, on the identification of self-emulsification region, as obtained by the ternary phase diagrams, and on the particle size distribution of the resulting emulsion form the self-emulsification. Thus, the solubility of a model drug (L294) was evaluated in several non-aqueous vehicles, including oils, surfactants, and co-surfactants/co-solvents; its vehicles compatibility was determined; and the ternary phase diagrams were defined to identify the self-emulsifying region. In vitro assays (particle size, polydispersity index, zeta potential, and turbidity) were performed to characterize the formulations performance. From preliminary results, Labrafac PG oil, Labrasol surfactant, and Transcutol HP co-surfactant showed to be the most promising for SEDDS development, and its phase diagram resulted in eight self-emulsifying formulations, containing different compositions, which presented particle size around 100 ± 10 nm. Therefore, the components of SEDDS formulation (Labrafac PG, Labrasol, and Transcutol HP) were selected aiming to improve L294 oral bioavailabilityDoutoradoDesenvolvimento de Processos BiotecnologicosDoutora em Engenharia Quimic