Peach Palm Fruit (Bactris gasipaes) Peel: A Source of Provitamin A Carotenoids to Develop Emulsion-Based Delivery Systems.

The peach palm fruit (Bactris gasipaes) peel is a byproduct after fruit consumption. The peel flour of two varieties (yellow and red) was separately obtained by hot air drying and was subsequently milled. The proximate analysis showed that the red variety exhibited higher protein, fat, and fiber contents than the yellow one. A higher carotenoid (836.5 ± 24.5 µg/g), phenolic compounds (83.17 ± 1.76 mg GAE/100 g), and provitamin A activity (33.10 ± 0.83 µg retinol/g) were found in the cooked red variety. The carotenoid and phenolic compositions were analyzed by HPLC-PDA-MS, finding ß-carotene and γ-carotene to be major compounds. The effect of thermal treatment increased the amount of these provitamin A carotenoids and lycopene, which were detected only in the red variety. Among phenolic compounds, procyanidin dimer (isomer I), feruloyl quinic acid, and several apigenin C-hexosides were identified as major constituents of peach palm epicarp. A carotenoid-rich emulsion-based delivery system was obtained after the optimization (RSM model) of carotenoid extraction with ultraturrax and sunflower oil and further development of an ultrasound-assisted emulsion. The best conditions for a stable emulsion were 73.75% water, 25% carotenoid-rich oil extract, 1.25% emulsifiers, and 480 W of ultrasonic power for 5 min. The optimized emulsion had a total carotenoid content of 67.61 µg/g, Provitamin A activity of 3.23 ± 0.56 µg RAE/g, droplet size of 502.23 nm, polydispersity index of 0.170, and zeta potential of -32.26 mV. This emulsion was chemically and physically stable for 35 days at 30 ± 2 °C, showing potential as a food additive with biofunctional properties. The strategy here developed is an economical and environmentally friendly process that allows the reuse of the byproduct of B. gasipaes.

Estudio de un sistema microparticulado que contiene aceite de tomillo (Thymus vulgaris) y de su aplicación potencial como promotor de crecimiento en la producción de pollos de engorde

Introducción: es conocida la actividad del aceite esencial de tomillo como promotor de crecimiento en pollos de engorde, pero su aplicación directa en producción se dificulta debido a su inestabilidad asociada a su alta volatilización. Objetivo: desarrollar un microencapsulado que incluya al aceite esencial de tomillo y se evalúe su desempeño en campo. Metodología: la técnica empleada para la microencapsula-ción fue la de secado por aspersión, utilizando como biopolímeros goma arábiga (GA), maltodextrina (M) o almidón de ñame succinatado (AÑS). Se establecieron las condiciones de emulsificación (paso previo a la microencapsulación), así como las condiciones para la obtención de las micropartículas, mediante la aplicación de un diseño estadístico experimental (DEE). Adicionalmente, se caracterizó la morfología, estabilidad, comportamiento de liberación y desempeño en campo de la formulación obtenida bajo las condiciones definidas. Resultados: se seleccionaron las matrices de los biopolímeros GA/M y GA/M/AÑS que conformaron el material de recubrimiento de las micropartículas. La eficiencia de encapsulación fue de 87,5 %, su tamaño de partícula de 74,5 µm, su índice de dispersión de 2,4 y tuvo un rendimiento de 48,5%. El ensayo de estabilidad demostró que la cubierta polimèrica ejerce cierta protección a la pérdida del aceite esencial. Los estudios de liberación evidenciaron la modulación de la liberación del activo. El estudio en campo demostró que el sistema microparticulado presenta un comportamiento estadísticamente similar al producto comercial que sirvió de comparador. Conclusión: este microencapsulado podría ser empleado como promotor de crecimiento en la producción de pollos de engorde.

SUMMARY Introduction: The biological activity of the thyme essential oil is known to work as growth promoter on broilers, but its direct applicability on production is difficult due to its instability associated to its volatilization. Aim: To develop a micro-encapsulated thyme essential oil and its performance in diets for broiler chickens. Methodology: The technique used for the microencapsulation was the spray drying process, using the Gum Arabic (GA), Maltodextrin (M) or Starch Yam succinate (SYS) as biopolymers. The emulsification conditions (previous step to the micro-encapsulation) and the conditions to obtain the microparticles were stablished, through the implementation of a statistical experimental design (SED) The formulation obtained under defined conditions is additionally characterized in terms of morphology, stability, release behavior and field performance. Results: The biopolymer matrixes GA/M and GA/M/SYS were selected for the covering material of the microparticles. The encapsulation efficacy was 87.5 %, its particle size was 74.5 [zm, the dispersity index 2.4 and a yield of 48,5%. The stability test proved that polymeric cover exerts some protection to the loss of the essential oil. The release studies demonstrated the release modulation of the active ingredient. The field study proved that the microparticulate system presents a statistical behavior like the commercial product used as comparator. Conclusion: This approach suggests that this microencapsulation method could be used as a growth promoter in the production of broiler chickens.

Introdução: a atividade do óleo essencial de tomilho como promotor de crescimento em frangos de corte é conhecida, mas sua aplicação direta na produção é difícil devido à sua instabilidade associada à sua alta volatilização. Objetivo: desenvolver um microencapsulado que inclua óleo essencial de tomilho e avaliar seu desempenho em campo. Metodologia: a técnica utilizada para microencapsulação foi a secagem por spray dryer, utilizando como biopolímeros goma arábica (GA), maltodextrina (M) ou amido succinato de inhame (ASI). As condições de emulsificação (etapa anterior à microencapsulação) foram estabelecidas, bem como as condições de obtenção das micropartículas, através da aplicação de um desenho estatístico experimental (DEE). Adicionalmente, foram caracterizados a morfologia, estabilidade, comportamento de liberação e desempenho em campo da formulação obtida nas condições definidas. Resultados: foram selecionadas as matrizes biopoliméricas GA/M e GA/M/AÑS que formaram o material de revestimento das micropartículas. A eficiência de encapsulamento foi de 87,5 %, seu tamanho de partícula foi de 74,5 [zm, seu índice de dispersão foi de 2,4 e teve um rendimento de 48,5%. O teste de estabilidade mostrou que a cobertura polimérica exerce alguma proteção contra a perda de óleo essencial. Os estudos de liberação evidenciaram a modulação da liberação do princípio ativo. O estudo de campo mostrou que o sistema microparticulado apresenta comportamento estatisticamente semelhante ao produto comercial que serviu de comparador. Conclusão: este microencapsulado pode ser utilizado como promotor de crescimento na produção de frangos de corte.

Experimental Solution of Chitosan and Nanochitosan on Wettability in Root Dentine: In Vitro Model Prior Regenerative Endodontics.

AIMS: To compare the effect of CS and CSnp on the wettability in root dentine with other irrigation protocols with an experimental in vitro model prior regenerative endodontics. Methods and Material. An in vitro experimental study that included eighty hemisected human root distributed into 8 groups: G1- distilled water; G2- 1% NaOCl/17% EDTA; G3- hypochlorous acid 0.025% HOCl, G4- 1% NaOCl/0.025% HOCl/17% EDTA, G5- 0.2 g/100 mL CS, G6- 1% NaOCl/0.2 g/100 mL CS, G7- CSnp, and G8- 1% NaOCl/CSnp. The wettability analysis calculated the contact angle (θ) between a drop of a blood-like and root dentinal surface; topographic characterization with scanning electron microscopy (SEM) quantified the diameter and number of tubules per area; spectroscopy infrared analyses (IR-S) identified chemical changes in the inorganic (phosphate/carbonate) and organic phase (amide/methyl). Statistical analysis: a linear mixed model, Kruskal-Wallis, and Holm-Bonferroni correction (P < 0.05) were used. RESULTS: Significantly higher wettability for G2 (27.1 (P = 0.0001)) was found. A mean value of 67°±°for experimental groups (P = 0.07) was found, and we did not identify differences between them. The SEM identified greater tubular opening and erosion for G4 and greater dentinal permeability per area for NaOCl/CS. IR-S identified dentinal organic integrity with NaOCl-CS/CSnp compared to organic reduction promoted for NaOCl/EDTA. CONCLUSIONS: This in vitro dentin determined an indirect association between the wettability and organic contents. The oxidative effect of NaOCl could be neutralized by CS-CSnp, and consequently, the wettability of the substrate decreases.

Benzoic acid complexes with Eudragit E100®: New alternative antimicrobial preservatives.

Given that the use of some preservatives in cosmetics has been restricted, novel alternative preservatives are needed. The aim of this study was to characterize the physicochemical and antimicrobial properties of two polyelectrolyte complexes (EuB100 and EuB75Cl25), which were developed through hot melt extrusion (HME) using benzoic acid (BA) and Eudragit E100. Based on phase diagrams and an experimental statistical design, the solubility of the acid in the polymer and the HME conditions were established. Intermolecular interactions were evaluated through Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and X-ray powder diffraction (XRPD). Release behavior was determined for the systems. Antibacterial activity and ζ-potential were determined on Escherichia coli. FTIR revealed acid-base interaction, and XPS showed that the percentages of protonated nitrogen N1s were 13.5% for EuB100 and 20.3% for EuB75Cl25. The BA released showed a non-Fickian behavior, and a satisfactory antibacterial activity against E. coli was demonstrated at pH 6.9. The complexes modified ζ-potential, destabilizing the membrane functionality of E. coli. These complexes are potential antimicrobial preservatives with a greater spectrum of action, with bactericidal activity against E. coli in a wider pH range than uncomplexed BA, even at pH 6.9.

Phospholipid-Conjugated PEG-b-PCL Copolymers as Precursors of Micellar Vehicles for Amphotericin B.

Amphotericin B (AmB) is a widely used antifungal that presents a broad action spectrum and few reports on the development of resistance. However, AmB is highly toxic, causing renal failure in a considerable number of treated patients. Although when AmB is transported via polymer micelles (PMs) as delivery vehicles its nephrotoxicity has been successfully attenuated, this type of nanoparticle has limitations, such as low encapsulation capacity and poor stability in aqueous media. In this research, the effect of modifying polyethyleglicol-block-poly(ε-caprolactone) (PEG-b-PCL) with 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) on the performance of PMs as vehicles for AmB was studied. PEG-b-PCL with two different lengths of a PCL segment was prepared via ring opening polymerisation and modified with DSPE at a post-synthesis stage through amidation. Upon modification with DSPE, a copolymer was self-assembled, thereby producing particles with hydrodynamic diameters below 100 nm and a lower critical micelle concentration than that of the raw copolymers. Likewise, in the presence of DSPE, the loading capacity of AmB increased because of the formed intermolecular interactions, such as hydrogen bonds, which also caused a lower aggregation of this drug. The assessment of in vitro toxicity against red blood cells indicated that the toxicity of AmB decreased upon encapsulation; however, its antifungal action against clinical yeasts was maintained and enhanced, as indicated by a decrease in its minimum inhibitory concentration.

Safety assessment of complex benzoic acid using in vitro permeation assays with pig skin in Franz cells / Evaluación de seguridad del ácido benzoico complejado empleando ensayos de permeación in vitro con piel de cerdo en celdas de Franz

SUMMARY Franz cells are one of the main tools to evaluate the transepithelial permeation of compounds through the performance of in vitro tests, these allows inferring the safety behavior of a compound in the skin. The objective of this research was to determine the permeation behavior of benzoic acid from complexes with polyelectrolytes (EuB 75 Cl 25 EuB 100), compared to benzoic acid without complexing, to infer its safety behavior. In a first phase, skin storage conditions were established comparatively evaluating the diffusion parameters (flow and permeation constant) and transepithelial water loss, using ears skin of freshly slaughtered pigs, stored in 1M NaCl at -2 °C for 3 days; it was worked under infinite doses conditions. Subsequently, the permeation test of two complexes between Eudragit E and benzoic acid, in comparison with benzoic acid, was carried out under finite dose conditions. The benzoic acid quantification was performed with an analytical method validated by HPLC-DAD. The results showed no significant differences showing that biological samples can be stored for 72 h under the conditions described. The permeation behavior of the complexed benzoic acid with respect to the free benzoic acid showed a better safety profile, since there was a lower permeation for the first case. These results show that complexation of benzoic acid could decrease the sensitivity reactions that it normally presents, based on the decrease in its permeation.

RESUMEN Las celdas de Franz son una de las herramientas para evaluar la permeación transe-pitelial de compuestos mediante la realización de ensayos in vitro, estos permiten inferir el comportamiento de seguridad de un compuesto en la piel. El objetivo de esta investigación fue determinar el comportamiento de permeación del ácido benzoico a partir de complejos con polielectrolitos (EuB 75 Cl 25 EuB 100) en comparación con el ácido benzoico sin complejar, para inferir su comportamiento de seguridad. En una primera fase, se establecieron las condiciones de almacenamiento de la piel comparando los parámetros de difusión (flujo y constante de permeación) y pérdida de agua transepitelial, empleando piel de orejas de cerdos recién sacrificados, almacenadas en NaCl 1M a -2°C por 3 días; se trabajó bajo condiciones de dosis infinitas. Posteriormente, se realizó el ensayo de permeación de dos complejos entre ácido benzoico y Eudragit E, en comparación con el ácido benzoico, bajo condiciones de dosis finitas. La cuantificación del ácido benzoico fue realizada con un método analítico validado por HPLC-DAD. Los resultados evidenciaron que las muestras biológicas pueden almacenarse durante 72 h en las condiciones descritas. El comportamiento de permeación del ácido benzoico complejado respecto al ácido benzoico libre demostró tener un mejor perfil de seguridad, puesto que hubo una menor permeación para el primer caso. Estos resultados demuestran que la complejación del ácido benzoico podría disminuir las reacciones de sensibilidad que normalmente este presenta, basándose en la disminución de su permeación.

Development of Amphotericin B Micellar Formulations Based on Copolymers of Poly(ethylene glycol) and Poly(ε-caprolactone) Conjugated with Retinol.

Amphotericin B (AmB) is a broad spectrum of antifungal drug used to treat antifungal diseases. However, due to the high toxicity of AmB, treated patients may suffer the risk of side effects, such as renal failure. Nanoencapsulation strategies have been reported to elicit low toxicity, albeit most of them possess low encapsulation efficiency. The aim of this research is to develop micellar delivery systems for AmB with reduced toxicity while maintaining its affectivity by employing retinol (RET)-conjugated amphiphilic block copolymers (ABCs) as precursors. Copolymers composed of poly(ε-caprolactone) (A) and polyethylenglycol (B) of types AB and ABA were synthesized by ring opening polymerization and subsequently conjugated with RET by Steglich esterification. 1H-NMR spectroscopy was used to corroborate the structure of copolymers and their conjugates and determine their molecular weights. Analysis by gel permeation chromatography also found that the materials have narrow distributions. The resulting copolymers were used as precursors for delivery systems of AmB, thus reducing its aggregation and consequently causing a low haemolytic effect. Upon conjugation with RET, the encapsulation capacity was enhanced from approximately 2 wt % for AB and ABA copolymers to 10 wt %. AmB encapsulated in polymer micelles presented improved antifungal efficiency against Candida albicans and Candida auris strains compared with Fungizone®, as deduced from the low minimum inhibitory concentration.

Validación de una metodología analítica por HPLC-DAD para la cuantificación de ácido benzoico complejado, en un ensayo de permeación transdérmica in vitro empleando piel de cerdo / Validation of an analytical methodology by HPLC-DAD for the quantification of complexed benzoic acid, in an in vitro transdermal permeation assay using pig skin

RESUMEN En el presente estudio se realizó la validación de una metodología analítica por cromatografía líquida de alta eficiencia con detector de arreglo de diodos (HPLC-DAD) para la cuantificación del ácido benzoico en complejos polielectrolíticos, obtenidos con Eudragit® E100. Para ello se evaluaron las características de desempeño determinando que la metodología es selectiva; lineal en el rango de concentraciones de 2 a 10 fíg/mL; precisa con un RSD inferior a un 2%; exacta con un porcentaje de recuperación de un 98,7% y se establecieron límites de cuantificación (LOQ) de 0,72 y de 1,56 (g/mL para el sistema y método respectivamente. De acuerdo a estos resultados, la metodología analítica es adecuada para evaluar la permeación in vitro, del ácido benzoico incluido en los complejos polielectrolíticos a través de piel porcina, empleando celdas de Franz.

SUMMARY This paper presents the studies carried out about the validation of an analytical methodology by high performance liquid chromatography with diode array detector (HPLC-DAD) for the quantification of benzoic acid in polyelectrolyte complexes obtained with Eudragit® E100. Performance characteristics of the methodology were evaluated, finding that this is selective; linear in the concentration range of 2 to 10 (g / mL; accurate with a RSD of less than 2%, exact with a recovery percentage of 98.7% and quantification limits of 0.72 and 1.56 fig / mL were established for the system and method respectively. According with this results, the analytical methodology is adequate to evaluate the in vitro permeation of benzoic acid, in polyelectrolyte complexes, through porcine skin in Franz cells.

Evaluación de la intercambiabilidad in vitro de diferentes marcas de tabletas de diclofenaco sódico disponibles en el mercado colombiano / In vitro evaluation of the interchangeability of different brands of diclofenac sodium tablets available in the Colombian market

Introducción. El diclofenaco sódico se clasifica como un antiinflamatorio no esteroide. Dado que es de venta libre, el paciente no tiene ningún seguimiento por parte de los equipos de salud, y como sus fuentes son múltiples, es necesario establecer la equivalencia entre ellas en estudios in vitro, que son los más prácticos y plantean un menor compromiso ético. Objetivos. Determinar la intercambiabilidad de diferentes marcas comerciales de diclofenaco sódico comparadas con el producto innovador mediante un estudio in vitro de tabletas comerciales de 50 mg, según los lineamientos del Sistema de Clasificación Biofarmacéutica (SCB). Materiales y métodos. Se desarrollaron pruebas físicas y químicas siguiendo las indicaciones de laedición 39 de la United States Pharmacopeia (USP). Para la cuantificación, se validó una metodología analítica según lo establecido en la mencionada farmacopea y la guía Q2 del International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Los perfiles de disolución y sus análisis se rigieron por lo establecido por la Organización Mundial de la Salud y las normas nacionales. Resultados. Todos los productos aprobaron las pruebas físicas. En cuanto a la disolución, la etapa ácida también fue superada por todas las marcas, pero una marca falló en la etapa alcalina. El análisis de similitud reveló que solo un producto fue equivalente al innovador y tres fueron supradisponibles, aunque dichas marcas también podrían considerarse equivalentes al producto innovador. Conclusiones. De las ocho marcas evaluadas, tres no cumplieron totalmente con la prueba de valoración del principio activo y del porcentaje de disolución; solo una marca fue intercambiable con el producto innovador y tres fueron supradisponibles comparadas con este, por lo cual no constituyen un riesgo para el paciente.

Introduction: Diclofenac sodium is classified as a non-steroidal anti-inflammatory drug. As diclofenac is an over-the-counter drug, its use among patients cannot be monitored by health teams in follow-up sessions. Given the multiple sources of diclofenac sodium, their interchangeability must be investigated, particularly in the form of in vitro studies, which are the most practical research type and entail minimal ethical commitment. Objectives: To determine the interchangeability of the different commercial brands of diclofenac sodium relative to the innovative product, this work carries out an in vitro study of eight commercial products of diclofenac sodium (50 mg) following the guidelines of the Biopharmaceutical Classification System. Materials and methods: Physical and chemical tests were developed following the guidelines of the 39th edition of the United States Pharmacopoeia. An analytical methodology was validated for the quantification of diclofenac according to the current pharmacopoeia and the Q2 guideline ofthe International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Dissolution profiles and their analyseswere governed by the regulations established by the World Health Organization and the national regulations. Results: All the products passed the physical tests. In the dissolution assays, the acid stage was overcome by all brands, but in the alkaline stage, one brand failed. The analysis of the similarities revealed that only one product was equivalent to the innovator and that three were supra-available, although these brands could also be considered equivalent to the innovator. Conclusions: Of the eight brands evaluated, three failed the test forthe active principle and the percentage of dissolution. Only one brand was found to be interchangeable with the innovator, and three were identified to besupra-availableand, thus, they do not present a risk for patients.

Acetilación del almidón de millo (Pennisetum glaucum) y evaluación de su aplicación como posible excipiente / Acetylation of millet starch (Pennisetum glaucum) and evaluation of its application as a possible excipienty

RESUMEN Los almidones nativos se utilizan en la fabricación de productos farmacéuticos, cosméticos y de alimentos. Tienen limitaciones que pueden mejorarse mediante modificaciones físicas, químicas o enzimáticas. Los almidones de millo y maíz (referencia) se modificaron por acetilación a tres niveles. Se evaluaron fisicoquímicamente y farmaco-técnicamente, para comparar el comportamiento de los almidones modificados frente al nativo. El almidón de maíz alcanzó mayores índices de sustitución. A mayor acetilación, la capacidad del almidón de incorporar agua mejoró, reflejándose en índices de hincha-miento y de sorción más altos, así como un incremento en la viscosidad. Se evidenció una mayor estabilidad de los geles del almidón de millo con menor tendencia a la sinéresis. La temperatura de gelatinización disminuyó a medida que aumentaba la acetilación, lo que permitiría obtener geles más rápido y con menor consumo de energía. El perfil de cristalinidad no se vio modificado sustancialmente. No se evidenciaron cambios importantes en las propiedades farmacotécnicas de los almidones modificados frente a los nativos. La captación de agua en el estado sólido favoreció la rápida desintegración en tabletas. Estos aspectos muestran un potencial del uso del almidón de millo acetilado en la industria farmacéutica y de alimentos como agente gelificante y desintegrante.

SUMMARY Native starches are very useful in the manufacture of pharmaceutical, cosmetic and food products. However, they have important limitations, which can be improved by physical, chemical or enzymatic modifications. Millet and maize starches (reference), were modified at three levels. Physicochemical and pharmaceutics tests were applied to evaluate changes in behavior. Under the same conditions, corn starch achieved higher substitution rates. Acetylation of starches, in more extensive, causes changes in the ability of the starch to trap water. The rates of swelling (swelling power) and sorption increase, as viscosity. There were an improve behavior in the characteristics of the gels and the water uptake. This behavior improves stabilization of gels, with less tendency to syneresis. The gelatinization temperature decreases as acetylation increases. By reducing the gelatinization temperature, gels are obtained in less time and with less energy consumption. The crystallinity profile do not change substantially. There were no significant changes in the pharmaceutics properties of the modified starches compared to the native ones. Higher water uptake in the solid state favors rapid disintegration in tablets. These aspects show a potential use of acetylated millet starch in the pharmaceutical and food industry as a gelling and disintegrating agent.

Peruvioses A to F, sucrose esters from the exudate of Physalis peruviana fruit as α-amylase inhibitors.

The fruit of Physalis peruviana is widely used in traditional Colombian medicine as an antidiabetic treatment. The aim of the study reported here was to identify the compounds responsible for the hypoglycemic activity using the α-amylase inhibition test. Bioguided fractionation of a dichloromethane extract of the sticky exudate that covers the fruit allowed the isolation and identification of three new sucrose esters, named as peruvioses C-E (1-3), along with the known peruvioses A (6), B (5) and F (4), the structures of which were elucidated by extensive NMR and MS experiments. These compounds proved to be responsible for the hypoglycemic activity observed in the extract. Peruviose D (2) showed the highest activity, with an inhibitory activity value of 84.8%. This is the first study to establish the potential of sucrose esters as α-amylase inhibitors and to explain the hypoglycemic effect that has traditionally been attributed to gooseberry fruit.

In vitro evaluation of the interchangeability of different brands of diclofenac sodium tablets available in the Colombian market / Evaluación de la intercambiabilidad in vitro de diferentes marcas de tabletas de diclofenaco sódico disponibles en el mercado colombiano

Introduction: Diclofenac sodium is classified as a non-steroidal anti-inflammatory drug. As diclofenac is an over-the-counter drug, its use among patients cannot be monitored by health teams in follow-up sessions. Given the multiple sources of diclofenac sodium, their interchangeability must be investigated, particularly in the form of in vitro studies, which are the most practical research type and entail minimal ethical commitment. Objectives: To determine the interchangeability of the different commercial brands of diclofenac sodium relative to the innovative product, this work carries out an in vitro study of eight commercial products of diclofenac sodium (50 mg) following the guidelines of the Biopharmaceutical Classification System. Materials and methods: Physical and chemical tests were developed following the guidelines of the 39th edition of the United States Pharmacopoeia. An analytical methodology was validated for the quantification of diclofenac according to the current pharmacopoeia and the Q2 guideline ofthe International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Dissolution profiles and their analyseswere governed by the regulations established by the World Health Organization and the national regulations. Results: All the products passed the physical tests. In the dissolution assays, the acid stage was overcome by all brands, but in the alkaline stage, one brand failed. The analysis of the similarities revealed that only one product was equivalent to the innovator and that three were supra-available, although these brands could also be considered equivalent to the innovator. Conclusions: Of the eight brands evaluated, three failed the test forthe active principle and the percentage of dissolution. Only one brand was found to be interchangeable with the innovator, and three were identified to besupra-availableand, thus, they do not present a risk for patients.

Introducción. El diclofenaco sódico se clasifica como un antiinflamatorio no esteroide. Dado que es de venta libre, el paciente no tiene ningún seguimiento por parte de los equipos de salud, y como sus fuentes son múltiples, es necesario establecer la equivalencia entre ellas en estudios in vitro, que son los más prácticos y plantean un menor compromiso ético.Objetivos. Determinar la intercambiabilidad de diferentes marcas comerciales de diclofenaco sódico comparadas con el producto innovador mediante un estudio in vitro de tabletas comerciales de 50 mg, según los lineamientos del Sistema de Clasificación Biofarmacéutica (SCB).Materiales y métodos. Se desarrollaron pruebas físicas y químicas siguiendo las indicaciones de la edición 39 de la United States Pharmacopeia (USP). Para la cuantificación, se validó una metodología analítica según lo establecido en la mencionada farmacopea y la guía Q2 del International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Los perfiles de disolución y sus análisis se rigieron por lo establecido por la Organización Mundial de la Salud y las normas nacionales.Resultados. Todos los productos aprobaron las pruebas físicas. En cuanto a la disolución, la etapa ácida también fue superada por todas las marcas, pero una marca falló en la etapa alcalina. El análisis de similitud reveló que solo un producto fue equivalente al innovador y tres fueron supradisponibles, aunque dichas marcas también podrían considerarse equivalentes al producto innovador.Conclusiones. De las ocho marcas evaluadas, tres no cumplieron totalmente con la prueba de valoración del principio activo y del porcentaje de disolución; solo una marca fue intercambiable con el producto innovador y tres fueron supradisponibles comparadas con este, por lo cual no constituyen un riesgo para el paciente.

A pH-responsive drug delivery matrix from an interpolyelectrolyte complex: preparation and pharmacotechnical properties

ABSTRACT Interpolyelectrolyte complexes, which constitute a type of polymeric material obtained through the self-assembly of oppositely charged polymers, exhibit interesting properties for use in the design of smart matrices for drug delivery. In the present study, a stoichiometric interpolyelectrolyte complex (SIPEC) composed of Eudragit E® and Eudragit® L100 was obtained at pH 6.0 and characterized and evaluated as a hydrophilic matrix for dexibuprofen. The formation of a SIPEC was monitored by ζ-potential measurements and characterized using infrared spectroscopy, thermal analysis, and scanning electron microscopy. The results indicated that a SIPEC obtained under these conditions can be used as a matrix for controlling the release of dexibuprofen and exhibit a pH-triggered release

Validación de una metodología analítica por HPLC-DAD para la cuantificación de cafeína en un ensayo de permeación in vitro empleando mucosa oral porcina / Validation of an analytical HPLC-DAD methodology for the quantification of caffeine in an in vitro permeation test using porcine buccal mucosa

RESUMEN En este artículo se presentan los resultados del desarrollo y validación de una metodología analítica por cromatografía líquida de alta eficiencia con detector de arreglo de diodos (HPLC-DAD) para la cuantificación de cafeína; se utilizó una columna C18 con detección UV a 273 nm y una fase móvil compuesta por agua/acetonitrilo (80:20 v/v) de modo isocrático. Las características de desempeño evaluadas permitieron comprobar que existe una adecuada selectividad, una linealidad entre 0,5 y 50 ug/mL, con una precisión expresada como RSD menor a 2%, un porcentaje de recuperación del 99,9% y unos límites de detección y cuantificación para el método de 2,99 y 2,69 ng/mL, respectivamente. El método propuesto es útil para determinar el perfil de permeación bucal de la cafeína mediante un estudio in vitro con celdas de Franz empleando membrana bucal porcina.

SUMMARY This paper presents the results of the development and validation of an analytical methodology through high performance liquid chromatography with a diode array detector (HPLC-DAD) for the quantification of caffeine, using a C18 reverse phase column with UV detection at 273 nm and a mobile phase consisting exclusively of water/acetonitrile (80:20 v/v). The evaluated performance characteristics allowed to verify that there is an adequate selectivity, a linearity between 0.5 and 50 /µg/mL, with precision expressed as RSD in less than 2%, a recovery rate of 99.9%, and limits of detection and quantification for the method of2.99 and 2.69 ng/mL respectively. The proposed method is useful for determining the oral permeation profile of caffeine by an in vitro study with Franz cells using porcine buccal membrane.

Interaction between DNA and Drugs Having Protonable Basic Groups: Characterization through Affinity Constants, Drug Release Kinetics, and Conformational Changes.

This paper reports the in vitro characterization of the interaction between the phosphate groups of DNA and the protonated species of drugs with basic groups through the determination of the affinity constants, the reversibility of the interaction, and the effect on the secondary structure of the macromolecule. Affinity constants of the counterionic condensation DNA-drug were in the order of 106. The negative electrokinetic potential of DNA decreased with the increase of the proportion of loading drugs. The drugs were slowly released from the DNA-drug complexes and had release kinetics consistent with the high degree of counterionic condensation. The circular dichroism profile of DNA was not modified by complexation with atenolol, lidocaine, or timolol, but was significantly altered by the more lipophilic drugs benzydamine and propranolol, revealing modifications in the secondary structure of the DNA. The in vitro characterization of such interactions provides a physicochemical basis that would contribute to identify the effects of this kind of drugs in cellular cultures, as well as side effects observed under their clinical use. Moreover, this methodology could also be projected to the fields of intracellular DNA transfection and the use of DNA as a carrier of active drugs.

In vitro intestinal permeability studies, pharmacokinetics and tissue distribution of 6-methylcoumarin after oral and intraperitoneal administration in Wistar rats

ABSTRACT 6-Methylcoumarin (6MC) is a semisynthetic coumarin with important in vitro and in vivo anti-inflammatory activity. In order to continue the pre-clinical characterization of this molecule, in vitro intestinal permeability, plasma profile and tissue distribution after oral administration in rats were studied. The permeability of 6MC was evaluated by the Caco-2 cellular model in both the apical-basal (A-B) and basal-apical (B-A) directions. The pharmacokinetics and biodistribution were evaluated in rats after oral and intraperitoneal administration at doses of 200 mg/kg. Transport experiments with Caco-2 cells showed that 6MC presented high permeability at all concentrations evaluated. This finding suggested that 6MC could be transported across the gut wall by passive diffusion. The plasma concentration-time curve showed that the maximum concentration (Cmax) was 17.13 ± 2.90 µg/mL at maximum time (Tmax) of 30 min for the oral route and Cmax 26.18 ± 2.47 µg/mL at 6.0 min for the intraperitoneal administration, with elimination constant of (Ke ) 0.0070 min-1 and a short life half time of (T1/2 ) lower that 120 min. The distribution study showed that 6MC has high accumulation in the liver, and widespread distribution in all the organs evaluated.

Estandarización de celdas de Franz para la realización de ensayos de liberación de fármacos a partir de complejos con polielectrolitos / Standardization of Franz cells to evaluate drugs release from drug-polyelectrolyte complexes

En el presente estudio se realizó la estandarización de las condiciones de operación de algunas celdas de Franz, sistema que permite realizar la evaluación de la liberación de compuestos biológicamente activos como una de sus aplicaciones. Para ello se seleccionaron y caracterizaron dos complejos obtenidos entre Eudragit® y ácido benzoico como modelos a emplear, de acuerdo con su solubilidad. Se evaluó su comportamiento de liberación en diferentes condiciones operacionales del ensayo y los resultados se evaluaron empleando el modelo de Korsmeyer-Peppas y el análisis estadístico correspondiente. El análisis de Korsmeyer-Peppas demostró que el mecanismo de liberación del ácido benzoico se ajusta a la ley de difusión de Fick, en algunos casos. Las condiciones operacionales definidas para el ensayo de liberación en las celdas de Franz fueron las siguientes: la concentración del ácido benzoico en la dispersión de complejo en el compartimento donor, 0,07%; la velocidad de agitación, 400 rpm; el volumen de muestreo, 1 mL y la frecuencia de muestreo según un esquema determinado. Se demostró la reproducibilidad del ensayo de liberación en las condiciones operacionales definidas, mediante análisis de varianza.

This paper presents the studies carried out about the standardization of the operational conditions of some Franz Cells; this system allows evaluating the drug release, among others. To this purpose, two Eudragit E- benzoic acid complexes were selected and characterized, as models due to their solubility. After that, the outstanding operational variables were established and evaluated at different levels. The delivery profiles analysis applying the Korsmeyer-Peppas model showed that the release mechanism of benzoic acid was Fick diffusion, in some cases. The operational conditions: benzoic concentration in the complex dispersion in the donor compartment, 0,07%; agitation speed, 400 rpm; volume (1 mL) and frequency sampling according to specific scheme, were determined. The delivery assay reproducibility was demonstrated in the established operational conditions by statistically analysis (ANOVA).

Mecanismos generales de cesión de principios activos a partir de matrices monolíticas hidrofílicas preparadas con éteres de celulosa / Overall mechanisms that rule the active pharmaceutical ingredient’s delivery process from hydrophilic matrices elaborated with ether cellulose

Las matrices hidrofílicas son uno de los sistemas de liberación controlados más empleados a escala mundial. El reconocido éxito global de este tipo de sistemas está ligado a su manufactura por medio de tecnología convencional para la obtención de comprimidos, además de su bajo costo. Estos sistemas han sido objeto de investigación desde hace ya algunas décadas, mediante el uso de técnicas como la creación de imágenes a partir de resonancia magnética, calorimetría de barrido diferencial y la espectroscopia dieléctrica de baja frecuencia, entre otras. Varios autores han estudiado los diferentes estados del agua dentro de una matriz, así como el estado y los cambios en los estados de los materiales en el tiempo, con el fin de estudiar los mecanismos de cesión de los activos a partir de las matrices, así como para buscar modelos matemáticos que describan la evolución de la concentración en el tiempo. En la actualidad se cuenta con modelos matemáticos de gran utilidad que permiten identificar dichos mecanismos a partir de un análisis de los parámetros de los modelos y que conducen finalmente a predecir la velocidad de liberación a partir de estos sistemas.

The hydrophilic matrices are one of the most used controlled delivery systems in the world, due to the simple technology and low cost. A number of publications, over the last decades, have reported investigations in regard with the mechanisms of drug release from hydrophilic matrices. Nevertheless, the mechanisms of drug release from these systems continue to be a matter of debate. Differential scanning calorimetry, low frequency dielectric spectroscopy and nuclear magnetic resonance have been used to examine the distribution of water within ether cellulose matrices, as well as to describe the state of the materials inside the device. The objective is to study the release and hydration rate of hydrophilic matrices in order to contribute to the rationalization of the design of these controlled release systems through mathematical modeling and to obtain a better knowledge of the processes that occur during the release of the drug.

Sistemas osmóticos de administración oral / Osmotically controlled oral drug delivery systems

Considerando que a nivel mundial el diseño de nuevos fármacos involucra un costo muy alto, tanto en tiempo como en dinero, la preocupación en los últimos años se ha centrado en diseñar y desarrollar medicamentos que controlen la liberación del activo, de manera que se les pueda dar un valor agregado a moléculas ya existentes, lo que significa una menor inversión en términos de costos. En este sentido, para la presente revisión se seleccionó el sistema de liberación osmótica, uno de los medicamentos de liberación controlada con más participación en el mercado en el mundo. En este escrito se muestran los aspectos fisicoquímicos relacionados con su formulación, las clases de sistemas osmóticos de administración oral existentes y sus aplicaciones, así como el estado del arte en este contexto. Hacia el futuro, estos sistemas osmóticos parecen ser muy promisorios, debido a sus ventajas y gran mercado potencial

Caracterización de algunas propiedades fisicoquímicas y farmacotécnicas del almidón de arracacha (Arracacia xanthorriza) / Characterization of some physicochemical and pharmaceutical properties of yellow Peruvian parrot (Arracacia xanthorriza)

El presente artículo sintetiza los resultados de diferentes ensayos de caracterización fisicoquímica y farmacotécnica del almidón de arracacha amarilla (Arracacia xanthorriza). La determinación del tamaño de partícula, realizada por microscopía óptica, muestra una distribución log-normal comprendida entre 5 y 35 µm; la forma, evaluada mediante microscopía electrónica de barrido, es poliédrica irregular; el rango de temperatura de gelatinización, determinado mediante calorimetría diferencial de barrido, está comprendido entre 49 - 55ºC; el contenido de amilosa, cuantificado mediante colorimetría, es cercano al 18 porciento; el comportamiento frente a la humedad relativa lo clasifica como un material moderadamente higroscópico y sus propiedades farmacotécnicas demuestran una baja voluminosidad, flujo pobre y buen desempeño bajo compresión