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Simvastatin (SIM) is widely prescribed to treat hyperlipidemia, despite its limitations, such as a short half-life and low oral bioavailability. To overcome these drawbacks, the development of a controlled-release formulation is desirable. This study aims to develop a microparticulate system based on cellulose acetate (ACT) obtained from Agave sisalana Perrine to promote a controlled SIM release. SIM-loaded microparticles (SMP) were prepared using the solvent emulsification-evaporation method. Several parameters were evaluated, including particle size, surface charge, morphology, encapsulation efficiency, thermochemical characteristics, crystallinity, and in vitro release profile. ACT exhibited favorable flow properties after acetylation, with a degree of substitution values superior to 2.5, as confirmed by both the chemical route and H-NMR, indicating the formation of cellulose triacetate. The obtained SMP were spherical with an average size ranging from 1842 to 1857 nm, a zeta potential of -4.45 mV, and a high SIM incorporation efficiency (98%). Thermal and XRD analyses revealed that SIM was homogeneously dispersed into the polymeric matrix in its amorphous state. In vitro studies using dialysis bags revealed that the controlled SIM release from microparticles was higher under simulated intestinal conditions and followed the Higuchi kinetic model. Our results suggest that ACT-based microparticles are a promising system for SIM delivery, which can improve its bioavailability, and result in better patient compliance.

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Este estudo objetivou estimar a prevalência do uso do cigarro eletrônico e a associação com fatores preditores. Trata-se de um estudo transversal, analítico, com amostra probabilística de universitários matriculados em um Centro Universitário de Montes Claros, Minas Gerais, Brasil no segundo semestre de 2022. A variável dependente referiu-se ao uso do cigarro eletrônico. As variáveis independentes referiram a fatores sociodemográficas, laborais e comportamentais. A associação entre as variáveis investigadas e a prevalência do uso do CE foi verificada pela análise bivariada e a regressão de Poisson. Foram entrevistados 730 universitários, com a média de idade de anos 22,56 (±6,25). Destes, 21,8 % faziam o uso cigarro eletrônico e após a análise multivariada manteve-se associado ao desfecho não ter companheiro (RP= 3,31; IC95% 1,04-10,48), morar com amigos/sozinho (RP=1,53; IC95% 1,07-2,18), ter histórico de usuários de cigarro eletrônico na residência (RP= 1,76; IC95%: 1,17- 1,89), consumir bebida alcoólica (RP= 3,07; IC95%: 1,72-5,49) e não praticar atividade física (RP= 3,37; IC95% 2,35-4,83). Conhecer sobre o cigarro eletrônico foi fator protetor (RP= 0,31 IC95% 0,20-0,46). Registrou-se elevada prevalência do uso do cigarro eletrônico, e manteve associados a fatores sociodemográficos e comportamentais. Esses achados chamam a atenção para a necessidade de novas medidas regulatórias, a fim de reduzir o uso desse dispositivo.

This study aimed to estimate the prevalence of e-cigarette use and the association with predictors. This is a cross-sectional, analytical study with a probabilistic sample of university students enrolled in a University Center of Montes Claros, Minas Gerais, Brazil in the second half of 2022. The dependent variable referred to the use of electronic cigarettes. The independent variables referred to sociodemographic, labor and behavioral factors. The association between the variables investigated and the prevalence of EC use was verified by bivariate analysis and Poisson regression. A total of 730 university students were interviewed, with a mean age of 22.56 (±6.25). Of these, 21.8% used electronic cigarettes and after multivariate analysis, it remained associated with the outcome of not having a partner (PR= 3.31; CI95% 1.04-10.48), living with friends/alone (PR=1.53; CI95% 1.07-2.18), having a history of e-cigarette users in the residence (PR= 1.76; CI95%: 1.17- 1.89), alcohol consumption (PR= 3.07; CI95%: 1.72-5.49) and not practicing physical activity (PR= 3.37; IC95% 2.35-4.83). Knowing about electronic cigarettes was a protective factor (PR= 0.31 CI95% 0.20-0.46). There was a high prevalence of e-cigarette use, and it was associated with sociodemographic and behavioral factors. These findings draw attention to the need for new regulatory measures in order to reduce the use of this device.

Este estudio tuvo como objetivo estimar la prevalencia del uso de cigarrillos electrónicos y la asociación con predictores. Se trata de un estudio analítico transversal con una muestra probabilística de estudiantes universitarios matriculados en un Centro Universitario de Montes Claros, Minas Gerais, Brasil, en el segundo semestre de 2022. La variable dependiente se refería al uso de cigarrillos electrónicos. Las variables independientes se refirieron a factores sociodemográficos, laborales y conductuales. La asociación entre las variables investigadas y la prevalencia de uso de CE fue verificada por análisis bivariado y regresión de Poisson. Fueron entrevistados 730 estudiantes universitarios, con una edad promedio de 22,56 (±6,25). De estos, 21,8% utilizaron cigarrillos electrónicos y después del análisis multivariado, se mantuvo asociado con el resultado de no tener pareja (RP= 3,31; IC95% 1,04-10,48), vivir con amigos/solo (RP=1,53; IC95% 1,07-2,18), con antecedentes de usuarios de cigarrillos electrónicos en la residencia (RP= 1,76; IC95%: 1,17- 1,89), consumo de alcohol (RP= 3,07; IC95%: 1,72-5,49) y no practicar actividad física (RP= 3,37; IC95% 2,35-4,83). El conocimiento de los cigarrillos electrónicos fue un factor protector (RP= 0,31 IC95% 0,20-0,46). Hubo una alta prevalencia de uso de cigarrillos electrónicos, y se asoció con factores sociodemográficos y de comportamiento. Estos hallazgos llaman la atención sobre la necesidad de nuevas medidas regulatorias para reducir el uso de este dispositivo.

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Drug-release systems have attracted attention over the last few years since they can be used as a substitute for traditional methods of drug delivery. These have the advantage of being directly administered at the treatment site and can maintain the drug at adequate levels for a longer period, thus increasing their efficacy. Starch-based films are interesting candidates for use as matrices for drug release, especially due to starch's non-toxic properties and its biocompatibility. Endophytic fungi are an important source of bioactive molecules, including secondary metabolites such as phenolic compounds with antioxidant activity. In the present study, cassava starch-based films were developed to act as release systems of phenolic compounds with antioxidant activity. The Amazonian endophytic fungus Aspergillus niger MgF2 was cultivated in liquid media, and the fungal extract was obtained by liquid-liquid partition with ethyl acetate. The starch-based films incorporated with the fungal extract were characterized in regards to their physicochemical properties. The release kinetics of the extract from the film and its antioxidant and cytotoxic properties were also evaluated. The films incorporated with the extract presented maximum release after 25 min at 37 °C and pH 6.8. In addition, it was observed that the antioxidant compounds of the fungal extract maintain their activity after being released from the film, and were non-toxic. Therefore, considering the promising physicochemical properties of the extract-incorporated films, and their considerable antioxidant capacity, the films demonstrate great biotechnological potential with diverse applications in the pharmacological and cosmetic industries.

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BACKGROUND: The successful use of semiochemicals to attract insects to traps is based on research on the most suitable compounds and their release profiles over time. Based on the group's promising results, matrices with a more adequate release profile and more eco-friendly properties for the release of 1-hexanol were developed. To use a more suitable prototype in the field, the most promising systems were added to a capsule and evaluated in a wind tunnel. Behavioral experiments were performed using the sand fly species, Lutzomyia longipalpis, to evaluate the efficacy of the proposed system. METHODS: Different delivery systems were developed by varying the polymer (gellan gum and pectin) ratio, crosslinker (aluminum chloride) concentration, and glutaraldehyde removal.The delivery systems were loaded with 1-hexanol, and their release profiles were evaluated using gravimetric analysis under ambient and high-humidity conditions. When the matrix system was placed inside a plastic container, modulations in the active release profile were observed and the system could be reused. Actid attraction behaviors of the sand fly species, Lu. longipalpis, were evaluated in a wind tunnel when exposed to 1-hexanol-loaded release systems at different times. RESULTS: Among the four formulations evaluated, System 2 (gellan gum and pectin in a 1:1 ratio with 5% aluminum chloride) exhibited the most promising release profile, with greater uniformity and longer compound release time. The maximum 1-hexanol release uniformity was achieved over a longer time, mainly every 24 h, under both ambient and high-humidity conditions. System 2 can be reused at least once with the same structure. The wind tunnel trials exhibited efficient activation and attraction of Lu. longipalpis to 1-hexanol after 24, 48, and 72 h in System 2 placed inside the capsules. CONCLUSIONS: The polymeric matrix supplemented with 1-hexanol and introduced in plastic capsules showed promising results in attracting sand flies. This system can be used as a solution for other attractive compounds as well as in other applications where their release needs to be controlled or prolonged.

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Nanoparticles of metal-organic frameworks (MOF NPs) are crystalline hybrid micro- or mesoporous nanomaterials that show great promise in biomedicine due to their significant drug loading ability and controlled release. Herein, we develop porous capsules from aggregate of nanoparticles of the iron carboxylate MIL-100(Fe) through a low-temperature spray-drying route. This enables the concomitant one-pot encapsulation of high loading of an antitumor drug, methotrexate, within the pores of the MOF NPs, and the collagenase enzyme (COL), inside the inter-particular mesoporous cavities, upon the formation of the capsule, enhancing tumor treatment. This association provides better control of the release of the active moieties, MTX and collagenase, in simulated body fluid conditions in comparison with the bare MOF NPs. In addition, the loaded MIL-100 capsules present, against the A-375 cancer cell line, selective toxicity nine times higher than for the normal HaCaT cells, suggesting that MTX@COL@MIL-100 capsules may have potential application in the selective treatment of cancer cells. We highlight that an appropriate level of collagenase activity remained after encapsulation using the spray dryer equipment. Therefore, this work describes a novel application of MOF-based capsules as a dual drug delivery system for cancer treatment.

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ABSTRACT Objective: This study estimates the prevalence in tobacco consumption and the associated factors in adolescents at official educational institutions in the municipality of Palmira. Methods: This was a cross-sectional analysis with an analytical component, including 205 high school students from six official schools. The analysis was performed through the SPSS statistics software version 24. Qualitative variables were expressed as ratios with their corresponding 95 % confidence intervals (CI). Quantitative variables were expressed as central tendency and dispersion measures, depending on the distribution of the variable. Finally, an odds ratio was calculated for the associated factors with a 95 % CI and the binary logistic regression model statistical model was used to adjust the variables. Results: The tobacco consumption's overall prevalence was 38.5%, CI 95 % (31.6-45.4 %); e-cigarette, 20 %, 95 % CI (14.2-25.7 %); cigarette, 18.5 %, 95 % CI (12.9-24.1 %) and hookah, 17.9 %, 95 % CI (12.1-23 %), with a greater incidence in women than men. The resulting associated factors were age (OR 3.17, CI 95 % [1.48-6.79]), a partner who smokes (OR 2.51, 95 % CI (1.36-4.63 %), friends who smoke (OR 7.0, 95 % CI [3.4-14.5]), and the possibility of buying individual cigarettes instead of a pack (OR 2.60, 95 % CI (1.26-5.3). Conclusions: Smoking habit's overall prevalence is higher than the one reported in adolescents. Female subjects reported greater and more frequent consumption of e-cigarettes.

RESUMEN Objetivo: estimar la prevalencia del consumo de tabaco y los factores asociados a esta práctica en adolecentes de instituciones educativas oficiales del municipio de Palmira. Métodos: estudio transversal con un componente analítico, que incluyó 205 estudiantes de bachillerato de seis colegios oficiales. El análisis se realizó con el programa estadístico SPSS versión 24. Las variables cualitativas se expresaron como proporciones, con sus respectivos intervalos de confianza (IC) al 95 %; y las variables cuantitativas como medidas de tendencia central y dispersión, según la distribución de la variable. Para los factores asociados, se calcularon Odds ratio con su IC al 95 %, y el ajuste de variables se realizó a través de regresión logística binaria. Resultados: la prevalencia global del consumo tabáquico fue del 38.5 %, IC 95 % (31.6-45.4 %); cigarrillo electrónico, del 20 %, IC 95 % (14.2-25.7 %); cigarrillo, del 18.5 %, IC 95 % (12.9-24.1 %); y narguile, del 17.9 %, IC 95 % (12.1-23 %), con más frecuencia en mujeres que en hombres. Los factores asociados fueron la edad (OR 3.17, IC 95 % [1.48-6.79]), tener novio que consuma tabaco (OR 2.51, IC 95 % (1.36-4.63 %), estar rodeado de amigos que fumen (OR 7.0, IC 95 % [3.4 -14.5]) y comprar cigarrillos sueltos (OR 2.60, IC 95 % (1.26-5.3). Conclusión: la prevalencia global del hábito tabáquico es superior a la reportada en adolescentes, mayor en el sexo femenino, con mayor frecuencia de consumo de cigarrillos electrónicos. Los factores asociados fueron la edad, tener novio o amigos que consuman tabaco y la posibilidad de comprar cigarrillos sueltos.

RESUMO Objetivo: estimar a prevalência do consumo de tabaco e os fatores associados a esse hábito em adolescentes de instituições educativas oficiais do município de Palmira, Colômbia. Métodos: estudo transversal com um componente analítico, que incluiu 205 estudantes do ensino médio de seis colégios oficiais. A análise foi realizada com o programa estadístico SPSS versão 24. As variáveis qualitativas foram expressas como proporções, com seus respectivos intervalos de confiança (IC) a 95 %; as variáveis quantitativas como medidas de tendência central e dispersão, segundo a distribuição da variável. Para os fatores associados, foram calculados Odds ratio com seu IC a 95 %, e o ajuste de variáveis foi realizado por meio de regressão logística binária. Resultados: a prevalência global do consumo de tabaco foi de 38,5 %, IC 95 % (31,6-45,4 %); cigarro eletrônico, de 20 %, IC 95 % (14,2-25,7 %); cigarro, de 18,5 %, IC 95 % (12,9-24,1 %); narguilé, de 17,9 %, IC 95 % (12,1-23 %), com mais frequência em mulheres do que em homens. Os fatores associados foram a idade (OR 3,17, IC 95 % [1,48-6,79]), ter parceiro(a) que consuma tabaco (OR 2,51, IC 95 % (1,36-4,63 %), estar rodeado(a) de amigos que fumam (OR 7,0, IC 95 % [3,4 -14,5]) e comprar cigarro solto (OR 2,60, IC 95 % (1.26-5.3). Conclusões: a prevalência global do hábito tabágico é superior à relatada em adolescentes, maior no sexo feminino, com mais frequência de consumo de cigarros eletrônicos. Os fatores associados foram a idade, ter parceiro(a) ou amigos que consumam tabaco e a possibilidade de comprar cigarros soltos.

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Caffeic acid (CA) molecules were immobilized in a layered inorganic host matrix based on zinc hydroxide structures with different starting interlayer anions, nitrate, and acetate. The chemical composition, structure, thermal stability, morphology, and surface of the host matrices and hybrid compounds were analyzed by X-ray diffraction (XRD), themogravimetric/differencial thermal analysis (TG/DTA), Fourier transform infrarred spectroscopy (FT-IR), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). Additionally, the surface charge of the materials was investigated using zeta potential at pH ~7. The results show an influence of the surface charge on the chemical, interaction, and structure of the resulting hybrid materials as a function of the starting layered structures. An expansion of the basal spacing to 10.20 Å for zinc hydroxide nitrate (ZHN), and a shrinkage to 10.37 Å for zinc hydroxide acetate (ZHA). These results suggest that the CA lies with a tilt angle in the interlayer region of the inorganic host matrix. The immobilization of CA is favored in ZHN, with respect to ZHA, because a single-layered phase was identified. A higher thermal stability at 65 °C was observed for ZHN-CA than for ZHA-CA. The evaluation of the release behavior showed a higher percentage of CA released from ZHN than ZHA, and the release mechanism was described by the Elovich model. The hybrid materials show potential characteristics for use as bioactive delivery systems.

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The self-assembled natural and synthetic polymers are booming. However, natural polymers obtained from native or modified carbohydrate polymers (CPs), such as celluloses, chitosan, glucans, gums, pectins, and starches, have had special attention as raw material in the manufacture of self-assembled polymer composite materials having several forms: films, hydrogels, micelles, and particles. The easy manipulation of the architecture of the CPs, as well as their high availability in nature, low cost, and being sustainable and green polymers have been the main positive points in the use of them for different applications. CPs have been used as building blocks for composite structures, and their easy orientation and ordering has given rise to self-assembled CPs (SCPs). These macromolecules have been little studied for food applications. Nonetheless, their research has grown mainly in the last 5 years as encapsulated food additive wall materials, food coatings, and edible films. The multifaceted properties (systems sensitive to pH, temperature, ionic strength, types of ions, mechanical force, and enzymes) of these devices are leading to the development of advanced food materials. This review article focused on the analysis of SCPs for food applications in order to encourage other research groups for their preparation and implementation.

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This review focus on the potential benefits, threats, and challenges of nanotechnology in animal reproduction. The investigation of gamete cells in high-resolution, production of nanobiosensors, and development of nanosystems aiming the sustained release of gonadotropins and steroid hormones are only some few examples of growing interest areas. Current facts and future prospects have highlighted the great potential of nanotechnology in reproduction field. Emerging concepts and technologies will be contextualized, reviewed, and explored in this review. (AU)

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This review focus on the potential benefits, threats, and challenges of nanotechnology in animal reproduction. The investigation of gamete cells in high-resolution, production of nanobiosensors, and development of nanosystems aiming the sustained release of gonadotropins and steroid hormones are only some few examples of growing interest areas. Current facts and future prospects have highlighted the great potential of nanotechnology in reproduction field. Emerging concepts and technologies will be contextualized, reviewed, and explored in this review.

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N,N-diethyl-meta-toluamide (DEET) is a widely used insect repellent due to its high efficacy. In this work, micellar systems based on poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer were developed and studied for the purpose of controlling the release and cutaneous permeation of DEET, using concentrated solutions of the copolymer Pluronic F127 to form thermoreversible gels. The formulations presented thermoreversible gelation above 5°C and altered rheological behavior at 15 and 25°C. The presence of the drug drastically changed the sol-gel transition temperatures. The micrographs suggest that DEET induced the formation of anisotropic structures, and Maltese Crosses were observed. The formulation containing 10wt% DEET and 15wt% Pluronic F127 presented sustained drug release for up to 7h. DEET release profile followed the Higuchi kinetics model. There was a reduction of approximately 35% in the amount of DEET absorbed through the skin after 6h. About 62% of DEET from the formulation consisting of Pluronic F127 and DEET remain retained on the skin. The anisotropic structure may constitute a barrier to diffusion and thereby controlling the drug release effectively. These tests suggest that the tested samples exhibit safety profile greater than some commercially available products.

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INTRODUCCION: El tratamiento de la tuberculosis requiere de la administración conjunta de rifampicina (RIF) e isoniacida (ISO). RIF se descompone en medio ácido al producto 3-FRSV, que en presencia de ISO forma IH. La liberación secuencial de RIF en estómago e ISO en intestino podría llevar a un incremento en la estabilidad de RIF. En una etapa previa RIF e ISO se asociaron a los polielectrolitos carboximetilcelulosa (CMC) y ácido algínico (AA), respectivamente, para obtener los materiales portadores CMC-RIF y AA-ISO que permiten la liberación inmediata de RIF y sostenida ISO. Los mismos pueden ser comprimidos para formar matrices hidrofílicas polielectrolico-fármaco (MHPF).OBJETIVO: Evaluar el impacto de la liberación secuencial de RIF e ISO en la estabilidad de RIF en condiciones simulando el contenido gástrico.METODOS: Los estudios de liberación desde las MHPF MCM-RIF + AA-ISO se realizaron en fluido gástrico simulado, utilizando referencia soluciones de RIF o RIF + ISO y la matric CMC-RIF en las mismas condiciones. La evaluación se realizó durante 2 hs, a 37ºC utilizando el aparato 2. La cuantificación se realizó mediante un método de HPLC indicativo de estabilidad, que permitió identificar ambos fármacos y sus productos de degradación.RESULTADOS: La MHPF CMC-RIF presenta muy rápida velocidad de disolución. La combinación de las MHPF CMC-RIF y AA-ISO permite la liberación selectiva e inmediata de RIF en medio ácido, con mínimos niveles concominantes de ISO, permitiendo una reducción en la formación de IH. Este producto de descomposición ha sido asociado con incremento en los eventos hepatotóxicos asociados a la combinación de RIF e ISO. Sin embargo, CMC acelera la degradación de RIF a 3-FRSV.CONCLUSIONES: La liberación secuencial de RIF e ISO permite reducir la formación de IH y es una estrategia adecuada para el desarrollo de comprimidos bi-capa. La optimización de la estabilidad requiere la adecuación de la capa de liberación inmediata de RIF.

INTRODUCTION: Tuberculosis treatment requires the administration of a combination of rifampicin (RIF) and isoniazid (ISO). In acidic media RIF decomposes to 3-FRSV, which in the presence of ISO forms IH. The sequential release of RIF in the stomach and ISO in the intestine could lead to an increase in RIF stability. In a previous work RIF and ISO were associated to the polyelectrolytes carboxymethylcellulose (CMC) and alginic acid (AA) to obtain carrier material CMC-RIF and AA-ISO that allow immediate release of RIF sustained of ISO. These materials can be compressed to form swellable drug polyelectrolyte matrices (SDPM).OBJECTIVE: To evaluate the impact of the sequential release of RIF and ISO in the stability of RIF in conditions simulating gastric contents.METHODS: Release studies were carried out from SDPM CMC-RIF + AA-ISO in simulated gastric fluid using as references RIF or RIF + ISO solutions under the same conditions. Samples were taken for 2 hs at 37ºC, using apparatus 2. The presence of both drugs and degradation products was analyzed by a stability indicating HPLC techinique.RESULTS: The SDPM CMC-RIF presented very fast release rate. The combination of SDPM CMC-RIF and AA-ISO permits selective and immediate release of RIF in acidic media, with minumum levels of ISO, with noticeable reduction of IH formation. This product has been associated with an increased frequency in hepatotoxic events associated with RIF and ISO combination. However, CMC accelerated degradation of RIF to 3-FRSV.CONCLUSIONS: Sequential release of RIF and ISO allowed a reduction in the formation of IH and seemed to be a suitable strategy for the development of bilayer tablets. Stability optimization should include adapting the immediate release layer of RIF.

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INTRODUCCION: El tratamiento de la tuberculosis requiere de la administración conjunta de rifampicina (RIF) e isoniacida (ISO). RIF se descompone en medio ácido al producto 3-FRSV, que en presencia de ISO forma IH. La liberación secuencial de RIF en estómago e ISO en intestino podría llevar a un incremento en la estabilidad de RIF. En una etapa previa RIF e ISO se asociaron a los polielectrolitos carboximetilcelulosa (CMC) y ácido algínico (AA), respectivamente, para obtener los materiales portadores CMC-RIF y AA-ISO que permiten la liberación inmediata de RIF y sostenida ISO. Los mismos pueden ser comprimidos para formar matrices hidrofílicas polielectrolico-fármaco (MHPF).OBJETIVO: Evaluar el impacto de la liberación secuencial de RIF e ISO en la estabilidad de RIF en condiciones simulando el contenido gástrico.METODOS: Los estudios de liberación desde las MHPF MCM-RIF + AA-ISO se realizaron en fluido gástrico simulado, utilizando referencia soluciones de RIF o RIF + ISO y la matric CMC-RIF en las mismas condiciones. La evaluación se realizó durante 2 hs, a 37ºC utilizando el aparato 2. La cuantificación se realizó mediante un método de HPLC indicativo de estabilidad, que permitió identificar ambos fármacos y sus productos de degradación.RESULTADOS: La MHPF CMC-RIF presenta muy rápida velocidad de disolución. La combinación de las MHPF CMC-RIF y AA-ISO permite la liberación selectiva e inmediata de RIF en medio ácido, con mínimos niveles concominantes de ISO, permitiendo una reducción en la formación de IH. Este producto de descomposición ha sido asociado con incremento en los eventos hepatotóxicos asociados a la combinación de RIF e ISO. Sin embargo, CMC acelera la degradación de RIF a 3-FRSV.CONCLUSIONES: La liberación secuencial de RIF e ISO permite reducir la formación de IH y es una estrategia adecuada para el desarrollo de comprimidos bi-capa. La optimización de la estabilidad requiere la adecuación de la capa de liberación inmediata de RIF.

INTRODUCTION: Tuberculosis treatment requires the administration of a combination of rifampicin (RIF) and isoniazid (ISO). In acidic media RIF decomposes to 3-FRSV, which in the presence of ISO forms IH. The sequential release of RIF in the stomach and ISO in the intestine could lead to an increase in RIF stability. In a previous work RIF and ISO were associated to the polyelectrolytes carboxymethylcellulose (CMC) and alginic acid (AA) to obtain carrier material CMC-RIF and AA-ISO that allow immediate release of RIF sustained of ISO. These materials can be compressed to form swellable drug polyelectrolyte matrices (SDPM).OBJECTIVE: To evaluate the impact of the sequential release of RIF and ISO in the stability of RIF in conditions simulating gastric contents.METHODS: Release studies were carried out from SDPM CMC-RIF + AA-ISO in simulated gastric fluid using as references RIF or RIF + ISO solutions under the same conditions. Samples were taken for 2 hs at 37ºC, using apparatus 2. The presence of both drugs and degradation products was analyzed by a stability indicating HPLC techinique.RESULTS: The SDPM CMC-RIF presented very fast release rate. The combination of SDPM CMC-RIF and AA-ISO permits selective and immediate release of RIF in acidic media, with minumum levels of ISO, with noticeable reduction of IH formation. This product has been associated with an increased frequency in hepatotoxic events associated with RIF and ISO combination. However, CMC accelerated degradation of RIF to 3-FRSV.CONCLUSIONS: Sequential release of RIF and ISO allowed a reduction in the formation of IH and seemed to be a suitable strategy for the development of bilayer tablets. Stability optimization should include adapting the immediate release layer of RIF.

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INTRODUCCIÓN: Rifampicina es inestable en medio ácido, y su descomposición es acelerada por isoniazida. El desarrollo de una formulación que permita la iberación secuencial de rifampicina (en estómago) e isoniazida (en intestino) podría superar este inconveniente. OBJETIVO: Obtener materiales portadores de rifampicina e isoniazida mediante acomplejamiento con polielectrolitos y caracterizarlos para determinar su utilidad en el desarrollo de sistemas de liberación sitio-específica, en combinación a dosisfija. MÉTODOS: Se utilizaron carboximetilcelulosa (CMC) y ácidoalgínico (AA) como polielectrolitos modelo. Se obtuvieron series de complejos CMC-rifampicina y AA-isoniazida. Se caracterizó el tipo de interacción, la capacidad de carga y las características reológicas de los materiales sólidos que, tras ser compactados bajo la forma de matrices simples o mixtas, fueron sometidos a ensayos de liberación en medios biorrelevantes. RESULTADOS: La interacción entre los grupos involucrados fue iónica, con una capacidad de carga del 100%. Los materiales presentaron propiedades de flujo desfavorables, con mejora por granulación. Las matrices liberaron rápidamente rifampicina en medio ácido con mínimos niveles concomitantes de isoniazida. La matriz seleccionada presentó liberación modulada de isoniazida, completada al cabo de 3 horas en un medio que simulaba el contenido intestinal. CONCLUSIONES: Los nuevos materiales pueden ser utilizados en el desarrollo de una formulación oral de liberación sitio-específica, capaz de mejorar la efectividad, reducir efectos adversos e incrementar la estabilidad de rifampicina.

INTRODUCTION: Rifampicin is unstable in acidic medium and its decomposition is accelerated by isoniazid. The development of a formulation to allow the sequential release of rifampicin (in stomach) and isoniazid (in gut) could overcome this problem. OBJECTIVE: To obtain materials with rifampicin and isoniazid, loaded in polyelectrolyte polymers and characterize them in order to determine their utility in the development of oral delivery systems for site-specific fixeddose combination. METHODS: Carboxymethyl cellulose (CMC) and alginic acid (AA) were used as polyelectrolytes. Series of complexes CMC-rifampicin and AA-isoniazid were obtained. The type of interaction, loading capacity and rheological properties were characterized in solid materials, which after compaction under simple or combined matrixes were testedin biorrelevant media. RESULTS: The interaction between components was ionic, and loading capacity was 100%.The powders showed unfavorable flow properties, improving by granulation. Release of rifampicin in acidic medium was fast, with minimal concomitant levels of isoniazid. The selected matrix showed a controlled release of isoniazid, which was completed after 3 hours in simulated intestinal media. CONCLUSIONS: The new materials can be used for the development of site specific oral formulations of rifampicin and isoniazid. They may lead to improved effectiveness, reduced side effects and higher rifampicin stability.

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