Search

Ammoniacal nitrogen and long chain fatty acids (LCFA) are common inhibitors of the anaerobic digestion process. However, the interaction between these inhibitors has received little attention. Understanding the interaction between these inhibitors is important to optimise the operation of anaerobic digesters treating slaughterhouse waste or using fat, oil and grease (FOG) as co-substrate among others. To study the interaction between ammoniacal nitrogen and LCFA inhibition, 20 different conditions were trialled in mesophilic batch tests. Experimental conditions included 5 mixtures between slaughterhouse wastewater and LCFA (100:0, 75:25, 50:50, 20:80, 0:100 on a VS basis), each one tested at 4 different ammoniacal nitrogen concentrations (0, 1, 3, 6 gNadded·L-1). Experimental and modelling results showed that ammoniacal nitrogen inhibition was less severe in LCFA-rich mixtures, indicating that LCFA mitigated ammoniacal nitrogen inhibition to a certain extent. However, the positive interaction between inhibitors did not only depend on the LCFA concentration. A protective LCFA coat that limited the diffusion of free ammonia into the cell and/or provided a localised lower pH in the vicinity of the microbial cell could explain the experimental results. However, ammoniacal nitrogen and LCFA inhibition comprise up to 6 different but interrelated inhibitors (i.e. NH3, NH4+, LCFA, VFA, H2 and pH) and therefore the specific mechanism could not be elucidated. Nonetheless, these results suggest that LCFA do not exacerbate TAN-related inhibition and that LCFA-rich substrates can be utilised as co-substrates in mesophilic N-rich digesters.

The objective of this research was to evaluate the anaerobic co-digestion of guinea pig manure (CY) with Andean agricultural residues such as amaranth (AM), quinoa (QU) and wheat (TR) in batch biodigesters under mesophilic conditions (37⁰C) for 40 days. As microbial inoculum, sewage treatment sludge was used in two inoculum/substrate ratios (ISR of 1 and 2). In terms of methane production, the best results occurred in the treatments that contained AM and QU as co-substrate and an ISR of 2. Thus, the highest methane production occurred in the CY:AM biodigesters (25:75) and CY:QU (25:75) with 341.86 mlCH4/g VS and 341.05 mlCH4/g VS, respectively. On the other hand, the results showed that methane production with an ISR of 2 was more feasible for guinea pig waste, where the methane fraction of the biogas generated was in a range of 57 and 69%. The kinetics of methane production from these raw materials was studied using five kinetic models: modified Gompertz, logistic equation, transfer, cone, and Richards. The cone model was the one that best adjusted the experimental values ​​with those observed with an r2 of 0.999 and an RMSE of 1.16 mlCH4/g VS. Finally, the highest biodegradability was obtained in the CY-AM biodigesters (25:75) with 67.92%.

The objective of this work was to develop a simple spectrophotometric method for determining antibiotic florfenicol in Eudragit nanocapsules. Regression curve of the method is linear in a concentration range of 80 – 480 μg/mL (correlation coefficient, 0.9998) at a selected wavelength of 270 nm. The limits of detection and quantification are 0.4 μg/mL and 1.2 μg/mL, respectively. The developed method demonstrated good inter-day and intra-day precision with RSD < 2. The percentage recovery of florfenicol was within 99.56 – 99.90%. In conclusion, the proposed method is specific, reproducible, accurate, and robust for the determination of florfenicol in Eudragit nanocapsules with detection at 270 nm in 95% confidence interval.

This study aims to evaluate the effects of the co‐digestion of agricultural residues with manure from camelids from the Andean zone. Different combinations of llama manure (LM) and vicuñas (VM) were made with amaranth (AS), quinoa (QS), and wheat (WS) residues. They were fermented using sewage sludge as inoculum. The co‐digestion was evaluated under mesophilic conditions for 40 days. The ratios of volatile substances of substrate / co‐substrate evaluated were 0:100; 25:75; 50:50, 75:25, and 100:0. Two substrate / inoculum ratios (SIR 1:1 and SIR1:2) were also evaluated. The results indicate that the maximum methane accumulation rate is obtained in SIR 1:1 for a VM‐AS ratio (25:75) with 540 mL/g volatile solid (VS). In general, the results did not increase with the increase in inoculum; rather, the tendency to improve methane yield is associated with an increase in the amount of agricultural residues, mainly AS. Regarding the kinetic modeling, the transfer model is the one that best adjusted the predicted values to those observed with an r2 between 0.991 and 0.999, and an RMSE value between 2.06 and 13.62 mL/g (volatile solid) VS. Finally, all the trials presented synergistic effects in their co‐digestion except the digesters formed by LM‐AS, LM‐QS and LM‐WS of SIR 1:2. These presented antagonistic effects in which the addition of the co‐substrate generated competition with the substrates, reducing methane production. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd

The aim of this work was to optimize unidirectional buccal patches loaded with metoprolol (MT-MBPs) to provide adequate mucoadhesive and water uptake properties as well as controlled drug release for the effective treatment of different cardiovascular diseases. The patches were prepared layer-by-layer using the solvent casting method. A central composite design was employed to statistically optimize the formulation variables. Chitosan and Pluronic® F-127 (poloxamer 407) concentrations were chosen as the independent variables, while ex vivo mucoadhesive force, ex vivo residence time, in vitro water uptake (%), and in vitro drug release (%) were to be considered the dependent variables. The optimized formulation was also characterized and evaluated in terms of morphology, thermal behavior, tensile strength, elongation at break, and ex vivo drug permeation. The optimized MT-MBPs were successful in terms of mucoadhesive force (3.58 ± 0.62 N), residence time (342.67 ± 17.21 min), and water uptake at 1 h (24.53 ± 3.62%). A controlled drug release was obtained for 8 h. Thermal and morphologic analyses demonstrated that metoprolol was homogeneously distributed throughout the microporous chitosan-based polymer matrix. Furthermore, the MT-MBPs exhibited a tensile strength of 3.76 ± 0.55 N/mm2 and an elongation at break of 36.52 ± 13.88%. The results of ex vivo permeation through pig buccal mucosa indicated that therapeutic metoprolol concentrations can be reached by using a patch of 5.62 cm2. Optimal composition of the MT-MBPs included 2.9% (w/v) and 2.6% (w/v) of chitosan and Pluronic® F-127, respectively, which constitutes the most suitable makeup for metoprolol buccal delivery.

The objective of this research is to experimentally evaluate the anaerobic co-digestion of slaughterhouse residues in the city of Guaranda with straw residues from agriculture, such as: amaranth, quinoa and wheat. The study was carried out on a laboratory scale using 311 ml biodigesters under mesophilic conditions of 37 °C. Anaerobic co-digestion resulted in methane yields of 407 ml CH4/g VS, with a methane content in the biogas of 77% for the mixture of slaughterhouse waste and quinoa (RM-QU (25:75)). The increase in inoculum in the mixtures composed of slaughterhouse residues and quinoa increased the biodegradability between 17 and 22%. However, in the mixtures of slaughterhouse waste and amaranth (RM-AM (0:100)), a further increase in inoculum decreased biodegradability by 5%. To predict and simulate methane production, 5 kinetic models were used: modified Gompertz, logistic equation, transfer, cone and Richards. The cone model was the one that best adjusted the experimental values ​​with those predicted with an R2 of 0.982 to 0.999 and RMSE of 0.61 to 6.92 ml CH4/g VS. The calculation of the theoretical yield was carried out by stoichiometry and elemental analysis of the samples. Theoretical yields ranged between 480-564 ml CH4/g VS for all mixtures of RM with agricultural residues.

This paper evaluates the anaerobic digestion of agricultural waste, manure and slaughterhouse residues of species typical of the Andes, such as llama, vicuna and guinea pig; quinoa, amaranth and wheat straw in order to be able to use them as a renewable energy source and boost rural development in the region. Has been used sludge from a WWTP as inoculum, evaluating the effect of two relationships between the substrate and inoculum (RSI) for both livestock and agricultural waste. The highest cumulative maximum methane production rate was obtained for the residues of flame manure and quinoa straw for an RSI of 1:2 with productions of 376.08 ml CH4/g SV and 377.02 ml CH4/g SV respectively. In these materials an RSI of 1:2 obtained increases of 22.56% and 37.54% compared to the RSI 1:1. Also, the kinetic analysis showed that the modified Gompertz model is the one that best fits performance, with constant differences of 7.06% between the experimental and predicted values. On the other hand, the modified Gompertz model was adjusted to the experimental results with an r2 of (0.998) and an RMSE of 4.09 ml/g SV at 17.12 ml/g SV.

The effect of temperature variations recorded in eight meteorological stations in Yaqui Valley, Sonora, Mexico, on the tillering capacity and grain yield of wheat variety CIRNO C2008 in the growing cycles December 2016-May 2017 and December 2017-May 2018 was studied. In one of the sites, the crop canopy temperature was increased by +2°C with a T-FACE system (warming) based on the temperature recorded in the nearest meteorological station. With the two experimental variants, the abscisic (ABA) and gibberellic (GA) acid hormones were determined during tillering (initial tillering: 30 d after emergence and final tillering: 45 d after emergence) to explain their contribution to the tillering capacity response. A temperature variability of 1°C was observed in the cycle December 2017-May 2018, as compared to the previous cycle and between the evaluated sites. As a result of the temperature increase effect, the tiller number was significantly reduced. The experimental warming caused a highly significant decrease in the ABA content and an increase in the GA. The temperature variation found in Yaqui Valley had a negative and significant correlation with the grain yield in both experiment crop cycles, which demonstrated that global warming is reducing the tillering capacity and grain yield of wheat in Yaqui Valley. RESUMEN Se estudió el efecto de las variaciones de temperatura registradas en ocho estaciones meteorológicas del Valle del Yaqui, Sonora, México, en la capacidad de macollamiento y el rendimiento de grano de la variedad de trigo CIRNO C2008, en dos ciclos de cultivo. En uno de los sitios, la temperatura del dosel del cultivo se incrementó en 2°C por medio de un sistema T-FACE (calentamiento) usando como control la temperatura registrada en la estación meteorológica más cercana. En estos dos tratamientos, se determinaron las hormonas ABA y GA al inicio y final del macollamiento para explicar su contribución a la capacidad de macollamiento. Como resultado, se encontró una variabilidad de temperatura de 1°C en el ciclo de diciembre de 2017 a mayo de 2018 con respecto al anterior y también entre los sitios evaluados. Por efecto del aumento de la temperatura disminuyó el número de hijos. El contenido de ABA disminuyó por efecto del calor mientras que el de GA aumentó. La variación de temperatura encontrada en el Valle del Yaqui correlacionó negativamente con el rendimiento de grano en ambos ciclos de cultivos, demostrando que el calentamiento está reduciendo la capacidad de macollamiento y el rendimiento del grano de trigo en el Valle del Yaqui.

Aims: Biodegradable polymeric microneedles containing atorvastatin calcium were developed in order to improve the percutaneous absorption of the drug, useful for the treatment of hypercholesterolemia. Background: The use of physical enhancers like microneedles have shown good results to increase the delivery of drugs through the skin, the use of microneedles has very important advantages for transdermal drug delivery, for example, they are painless, easy to use and safe, they increase time interval of drug activity, dose, and reductions in adverse reactions, they also offer, the facility to remove the system instantly of the skin. Objective: Develop polymer microneedles loaded with a calcium atorvastatin and evaluate them by Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), bioadhesion, postwetting- bioadhesion, breaking strength, drug release test and in vitro percutaneous absorption studies to demonstrate the use of microneedles atorvastatin is able to cross the skin. Methods: The microneedles were made with poly (methyl vinyl ether-alt-maleic acid) as biodegradable polymer using the technique of casting in solution in a mold. After solidification these microneedles were characterized by Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), bioadhesion, post-wetting-bioadhesion, breaking strength, drug release test and in vitro percutaneous absorption studies. Results: In general, the performances were satisfactory for optimal formulation in terms of DSC with no interactions between drug and excipients, SEM shows microneedles with a conical shape, bioadhesion of 1570 g.f, post wetting-bioadhesion of 1503.4 g.f, breaking strength of 1566.7g.f that is sufficient to disrupt Stratum corneum, good drug release and a flux of 33.4 μg/cm2*h with a tLag of 15.14 h for the in vitro percutaneous absorption. Conclusion: The results indicate that it is possible to generate microneedles to increase the percutaneous absorption of calcium atorvastatin transdermally, with the potential to be used as an alternative to the oral route for the treatment of dyslipidemias.

Possibilities of anaerobic processing of substrates rich in sulphur were studied. High concentrations of sulphur cause problems when contained in biogas, as well as inhibition by sulphides in anaerobic processes. The impact of ferrous chloride on anaerobic processes, directly dosed to the anaerobic reactor was studied. This sulphur removal method is commonly known, though the objective of our study was to identify problems when it is applied on substrates rich in sulphur. Waste biomass from cystine production was used as substrate, which is produced in large quantities (17000 t/y) by Biotika, a.s. Slovenská Ľupča and requires processing; sulphur content range from 4 up to 5 % in the biomass. Specific biogas production was 0.410 m3/kg COD i.e. 0.737 m3/kg VSS, while 77 % sulphide inhibition occurred after several dose repetitions. Inhibition decreased to 25.4 % during long-term processing of cystine biomass in a mixed anaerobic reactor. Ferrous chloride dosing, however, resulted in high excess sludge generation, lower organic content in the sludge and high concentration of dissolved inorganic salts. These factors may lead to secondary problems in long-term processing of cystine biomass.

Dexmedetomidine is an imidazole derivative, with high affinity for α2 adrenergic receptors, used for sedation, analgesia and adjuvant anaesthesia. In this study, an analytical method for the quantification of dexmedetomidine in dried blood spots was developed, validated and applied. The drug was extracted from dried blood spot by liquid extraction; the separation was carried out by ultra high-resolution liquid chromatography in reverse phase coupled to tandem mass spectrometry method. An X Select cyano 5 μm HSS column (2.1 X 150 mm, Waters) and a mobile phase composed of 0.1% formic acid: acetonitrile [50:50 v/v], were used. The test was linear over the concentration range of 50 to 2000 pg/mL. The coefficients of variation for the intra and interday trials were less than 15%. The drug was stable under the conditions tested. The method was successfully applied for the quantification of 6 patients, aged 0 to 2 years, with classification ASA I, who underwent ambulatory surgeries, receiving a dose of 1 μg/Kg dexmedetomidine IV. The drug concentrations in the different sampling times were in the range of 76 to 868 pg/mL.

The microneedles technology has found applications in many health-related fields. For example, their application in drugs and vaccines delivery as well, as the determination of biomarkers, has been reported. They also have a place in the dermatology and cosmetic areas such as the treatment of wounds from burns, scars, acne, depigmentation, and alopecia will be shown. Microneedles are used in therapeutic applications and are manufactured using materials such as metal (steel, titanium, nickel), polymer (oly-glycolic acid (PGA), poly-lactide-co-glycolide acid (PLGA), poly-L-lactic acid (PLA), chitosan), glass, silicon, ceramic, carbohydrates (trehalose, sucrose, mannitol). Examples of application of microneedles and their advantages and disadvantages are discussed. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

During malolactic fermentation in wines, malic acid is transformed into lactic acid by the action of lactic acid bacteria. This process can be monitored on-line by measuring the velocity of a low intensity ultrasonic wave propagating through the medium. In this work, an experimental study of ultrasonic propagation velocity in laboratory mixtures of water–ethanol–malic acid and lactic acid is presented. A good correlation was found between the ultrasonic velocity and malic and lactic acid concentrations. These results could be used to predict the end-point of the malolactic fermentation process and show the great potential of this ultrasonic technique to determine malic and lactic acid concentrations during the malolactic fermentation process.

[EN] For the economically depressed communities such as of those in the Canton Guaranda, Ecuador, to generate their own energy, from organic waste is very important because they are sometimes insulated and its gas and electricity supply is very deficient. The aim of this research, was to determine the feasibility of anaerobic co-digestion of wasted cabbage from the town's market in Guaranda, Ecuador, and livestock manure. Two variables were studied: temperature of the process and the percentage of cabbage and livestock manure. Biogas quantity and kinetic parameters were evaluated. Kinetic model were analyzed by minimizing the mean percentage of error between the observed values (measured experimentally) and predicted, using the Runge-Kutta of order 4 for solving the system of differential equations obtained from mass balance. The results showed that a 50-50% ratio cabbage-manure at 30 degrees C temperature gave the highest production of biogas achieved is (389.47cm(3)N/g initial SV) with a composition of 61% methane. The kinetic parameters found were mu(max)=0.1053day(-1); Ks=0.1153mg/l; Y=0.00246g VSS /g COD and K-dec=0.001005day(-1)., This research work has been carried out inside the cooperation framework funded by the ADSIDEO program of the Centro de Cooperacion al Desarrollo (CCD) of Universidad Politecnica de Valencia (Spain), in collaboration with the Centro de Estudios de la Biomasa (CEB), Universidad Estatal de Bolivar, Guaranda, Ecuador. The participation of Dr. Sergio Perez in this work was possible thanks to funding from the Ecuadorian Government by means of the PROMETEO program, led by the Secretaria Nacional de Educacion Superior, Ciencia y Tecnologia (SENESCYT).

The progress of malolactic fermentation in red wines has been monitored by using ultrasonic techniques. The evolution of ultrasonic velocity of a tone burst 1 MHz longitudinal wave was measured, analyzed and compared to those parameters of oenological interest obtained simultaneously by analytical methods. Semi-industrial tanks were used during measurements pretending to be in real industrial conditions. Results showed that the ultrasonic velocity mainly changes as a result of the conversion by lactic acid bacteria of malic acid into lactic acid and CO2. Overall, the present study has demonstrated the potential of the ultrasonic technique in monitoring the malolactic fermentation process. (C) 2014 Elsevier B.V. All rights reserved.

Recently, sildenafil was introduced to treat pulmonary arterial hypertension (PAH); however, there are currently few studies on the pharmacokinetics of sildenalfil in children. Therefore, we aimed to carry out a pharmacokinetic study of sildenafil in children with PAH using a single dose. Twelve children diagnosed with PAH, consisting of with ten males and two females, were recruited for the study after obtaining written consent from their parents or guardians. Blood samples were obtained predose and at 0.25, 0.5, 1, 2, 4, 8 and 12 hours after the oral administration of 1 mg/kg of sildenafil using an extemporal pediatric formulation developed in our laboratory. The samples were analyzed using a previously validated high performance liquid chromatography method. A pharmacokinetic analysis using the WinNonlin 3.1 program that considered the Akaike information criterion (AIC) for selecting a more adjustable model was performed. The following pharmacokinetic parameters were obtained: maximal concentration (Cmax): 366±179 ng/mL, time to maximal concentration: 0.92±0.30 hours, elimination half-life (t1/2): 2.41±1.18 hours, total clearance (CLtot/F): 5.85±2.81 L/hour, volume of distribution (Vd/F): 20.13±14.5 L, absorption rate constants (Ka): 0.343 hour–1, elimination rate (Ke): 0.35 hour–1, area under curve from zero to infinity: 2061±618 ng/mL/hour. The data of all patients adjusted to the model of one compartment were corroborated using AIC. The parameters Ka, Ke and t1/2 were found to be similar to those reported in adults; however, the values of Cmax and Vd/F were significantly higher. Based on these findings, we propose that treatment regimen of sildenafil be adjusted in children with PAH.

Cigarette smoking is the primary cause of lung cancer, cardiovascular diseases, reproductive disorders, and delayed wound healing all over the world. The goals of smoking cessation are both to reduce health risks and to improve quality of life. The development of novel and more effective medications for smoking cessation is crucial in the treatment of nicotine dependence. Currently, first-line smoking cessation therapies include nicotine replacement products and bupropion. The partial nicotinic receptor agonist, varenicline, has recently been approved by the US Food and Drug Administration (FDA) for smoking cessation. Clonidine and nortriptyline have demonstrated some efficacy, but side effects may limit their use to second-line treatment products. Other therapeutic drugs that are under development include rimonabant, mecamylamine, monoamine oxidase inhibitors, and dopamine D3 receptor antagonists. Nicotine vaccines are among newer products seeking approval from the FDA. Antidrug vaccines are irreversible, provide protection over years and need booster injections far beyond the critical phase of acute withdrawal symptoms. Interacting with the drug in the blood rather than with a receptor in the brain, the vaccines are free of side effects due to central interaction. For drugs like nicotine, which interacts with different types of receptors in many organs, this is a further advantage. Three anti-nicotine vaccines are today in an advanced stage of clinical evaluation. Results show that the efficiency of the vaccines is directly related to the antibody levels, a fact which will help to optimize the vaccine effect. The vaccines are expected to appear on the market between 2011 and 2012.

Zaida Urbán-Morlán1, Adriana Ganem-Rondero1, Luz María Melgoza-Contreras2, José Juan Escobar-Chávez1,2, María Guadalupe Nava-Arzaluz1, David Quintanar-Guerrero11División de Estudios de Posgrado (Tecnología Farmacéutica), Facultad de Estudios Superiores Cuautitlán-Universidad Nacional Autónoma de México, Estado de México, México; 2Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso, Colonia Villa Quietud, MéxicoAbstract: Solid lipid nanoparticles (SLNs) have been used for carrying different therapeutic agents because they improve absorption and bioavailability. The aim of the study was to prepare lipidic nanoparticles containing cyclosporine (CyA) by the emulsification-diffusion method and to study their physicochemical stability. Glyceryl behenate (Compritol® ATO 888) and lauroyl macrogolglycerides (Gelucire® 44/14) were used as carrier materials. Nanoparticles with good stability were obtained with Gelucire®, while it was difficult to obtain stable systems with Compritol®. Systems with Gelucire® were characterized by particle size, Z-potential, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), entrapment efficiency and in vitro release. Particle size and Z-potential were evaluated for at least three months. With a high CyA content (≥60 mg) in Gelucire® SLNs, variations in size were greater and particle size also increased over time in all batches; this effect may have been caused by a probable expulsion of the drug due to the lipid’s partial rearrangement. While the Z-potential decreased 10 mV after three months, this effect may be explained by the superficial properties of the drug that make the molecules to be preferably oriented at the solid-liquid interface, causing a change in the net charge of the particle. SEM confirmed size and shape of the nanoparticles. DSC studies evidenced that CyA affects the lipid structure by a mechanism still unknown. The entrapment efficiency was higher than 92%, and CyA release from SLNs was relatively fast (99.60% in 45 min).Keywords: emulsification-diffusion method, solid lipid nanoparticles, glyceryl behenate, lauroyl macrogolglycerides, dispersion stability, cyclosporine

Cementum protein 1 (CEMP1) has been recently cloned, and in vitro experiments have shown functions as regulator of cementoblast behavior and inducer of differentiation of non-osteogenic cells toward a cementoblastic/osteoblastic phenotype. In this study, we have produced a full-length human recombinant CEMP1 protein in a human gingival fibroblast cell line. The purified protein ( hr CEMP1) has a M r 50,000. Characterization of hr CEMP1 indicates that its secondary structure is mainly composed of β-sheet (55%), where random coil and alpha helix conformations correspond to 35% and 10%, respectively. It was found that hr CEMP1 is N -glycosylated, phosphorylated and possesses strong affinity for hydroxyapatite. Even more important, our results show that hr CEMP1 plays a role during the biomineralization process by promoting octacalcium phosphate (OCP) crystal nucleation. These features make CEMP1 a very good candidate for biotechnological applications in order to achieve cementum and/or bone regeneration.

Purpose In response to the lack of pediatric formulations of metformin to control type 2 diabetes mellitus, hyperinsulinemic obesity, and dyslipidemias, we developed liquid formulations of metformin by dissolving 3 generic brands of 500-mg metformin *, *Trademark: Medimart® (Probiomed, Mexico). †, †Trademark: Farmacias del Ahorro® (Degort's Chemical, Mexico). ‡ ‡Trademark: Primer Nivel® (Pisa, Mexico). tablets in water sweetened with sucralose. The physicochemical stabilities of these drugs were assessed and compared with those of formulations made with the innovative brand of metformin. ∥ ∥Trademark: Glucophage® (Roche, Mexico). A method to measure metformin plasma levels was proposed and then tested in 2 healthy subjects. This method may be useful to survey treatment compliance in the future. The biological safety profiles of the metformin solutions were assessed preliminarily in a system of hormone-dependent cancer cells (human breast cancer MCF-7 cells). Methods Metformin solutions stored at 25°C exposed to light and at 25°C, 4°C, and 40°C protected from light, underwent physicochemical analysis by ultra-performance liquid chromatography with ultraviolet detection, the mobile phase consisting of 0.2 M potassium monobasic phosphate (pH 6.5), 4.6 mM sodium dodecyl sulphate (SDS), and acetonitrile (63:7:30) at a flow rate of 0.8 mL/min in a Symmetry C8 150 × 4.6 mm column (Milford, Massachusetts) at 40°C (236 nm). MCF-7 cells were grown in 96-well ELISA plates (2 × 10 5 cells/well) and were exposed to 10, 20, and 40 mg/mL sucralose § §Trademark: Splenda®; Johnson & Johnson, New Brunswick, New Jersey), Stevia rebaudiana (Svetia; Metco, S.A. de C.V., Mexico, D.F., Mexico), and metformin (50 mg/mL) for 48 hours. Cytotoxicity was determined using the WST-1 colorimetric assay (Roche, USA) in an Epoch ELISA reader (BioTek, Winooski, Vermont) at 440 nm. Findings All brands of metformin were stable at all storage conditions for up to 30 days and retained >90% of the initial amount. Sucralose and Stevia rebaudiana caused zero cytotoxicity (ANOVA, P ≤ 0.05). The ultra-performance liquid chromatography with ultraviolet detection method was adapted to determine metformin level in very small blood samples (40 μL), which was linear within the range of 20 to 600 ng/mL metformin (retention time 2 minutes). Metformin was physically and chemically stable within the processed blood for up to 30 days at 4°C. Implications Extemporaneous formulations of metformin may be developed at low cost from either the innovator or generic brands, and both sucralose and Stevia rebaudiana sweeteners may be well tolerated; however, the minimum amount of sweetener is recommended to avoid any endocrine disturbance. The analytical method is accurate and precise to clinically measure metformin levels in patients taking the extemporaneous formulation orally. Study registry identification number: 100/2013.

Sildenafil extemporaneous formulations, used to treat pulmonary arterial hypertension (PAH) in hospitalised children, must be also stable and uniform in content. In this study, we determinedcontent uniformity, stability and therapeutic efficacy of sildenafil in gelatine capsules containing5 mg from three brands (Viagra®, Maxifort® and Apodefil®). The powder from crushed tablets was distributed into 32 gelatine capsules for each brand. Content uniformity and stability at 25and 40°C were analysed by HPLC-UV (mBondapack C18 column, H2KPO4 35 mM (pH 6.0)/ acetonitrile (53:47 v/v), 0.8 ml/min). Therapeutic efficacy of unitary doses was assessed in 25 patients (14 boys and 11 girls), according to clinical improvement and systolic pulmonary arterial pressure (SPAP) decrease, before and after taking sildenafil. Unitary doses showedcontent uniformity (4.93 ± 0.327 ≈ 5 mg) and were stable for 30 days at 25 and 40°C. SPAPvalues decreased to normal in 64% of the patients. Dyspnoea disappeared in 85% (11/13) andcyanosis in 67% (6/9). Two children (8%) showed no therapeutic response. Individualised doses of sildenafil in gelatine capsules are stable, uniform in content, and therapeutically effective, being an alternative to treat PAH in hospitalised and ambulatory patients. Key words: Pulmonary hypertension, sildenafil capsule, children, unitary doses, content uniformity, stability, extemporaneous preparation.

This work focuses on the preparation and characterization of nanoparticles containing triclosan. Additionally, in vitro percutaneous permeation of triclosan through pig ear skin was performed, and comparisons were made with two commercial formulations: An o/w emulsion and a solution, intended for the treatment of acne. The nanoparticle suspensions were prepared by the emulsification-diffusion by solvent displacement method, using Eudragit® E 100 as polymer. All batches showed a size smaller than 300 nm and a positive Zeta potential, high enough (20-40 mV) to ensure a good physical stability. Differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) studies suggested that triclosan was molecularly dispersed in the nanoparticle batches containing up to 31% of triclosan, with good encapsulation efficiency (95.9%). The results of the in vitro permeation studies showed the following order for the permeability coefficients: Solution>cream≈nanoparticles; while for the amount retained in the skin, the order was as follows: cream>nanoparticles≈solution. Nanoparticles, being free of surfactants or other potentially irritant agents, can be a good option for the delivery of triclosan to the skin, representing a good alternative for the treatment of acne.

El objetivo del presente estudio fue desarrollar un metodo simple, selectivo y confiable para cuantificar acetaminofen y su metabolito toxico (NAPQI) de N-acetyl-p-benzoquinoneimine para estudios pediatricos con 100 μl las muestras de plasma, por deteccion de fase inversa HPLC y UV. El analisis se realizo mediante una columna C₁₈ y una elucion isocratica con acido formico en agua-metanol (70:30:0.15; v - v - v) como fase movil. Linealidad del metodo se ensayaron en el rango de 1-30 μg - mL de paracetamol y 10-200 μg - mL para la NAPQI, con un coeficiente de correlacion r = 0.999 para ambos compuestos y inter-intra-dia y coeficientes de variacion de menos del 13%. Se analizaron varios farmacos administrados comunmente Co para selectividad y no se observo ninguna interferencia con las determinaciones. Los limites de deteccion y cuantificacion de acetaminofen y NAPQI fueron 0.1, 0.1 y 1 μg - mL y 10 μg - mL respectivamente. El presente metodo puede utilizarse para controlar los niveles de paracetamol con 100 μl las muestras de plasma, que pueden ser utiles cuando se necesitan muestras muy pequenas ser analizados, como en la determinacion de la farmacocinetica o la monitorizacion de farmacos en plasma en ninos. Este ensayo tambien es capaz de detectar el NAPQI de farmaco vigilancia en los pacientes diagnosticados con intoxicacion por paracetamol.

The aim of this study was to prepare and characterize both physically and biopharmaceutically, a nortriptyline hydrochloride (NTP-HCl) patch formulated in chitosan.16 g of each chitosan patch formulation (I, II and III, see Table 1 ) was poured onto rectangular glass plates (64 cm²) at a height of 1 mm and dried for 24 h at room temperature. In order to characterize the chitosan patches, polarized microscopy, in vitro skin permeation studies by passive diffusion and iontophoresis and rheological and bioadhesion studies were performed.Polarized microscopy revealed the absence of aggregates and crystal forms of NTP-HCl in all transdermal patches after 30 days of storage. The rheological behavior of Patches I, II and III was predominantly elastic. The low level of adhesion of Patch III (containing PF-127 + 1-dodecanol) could be a result of the interactions between chitosan and PF-127 in the presence of 1-dodecanol. Patches I and II had approximately the same value of adhesion (≈ 60 mN.mm). The transdermal patch with chitosan, PF-127 and 1-dodecanol (Patch III) provided a reasonable flux of NTP-HCl across the skin compared with Patches I and II. Iontophoresis applied to the patches did not increase the penetration of NTP-HCl across the skin.The data suggest that Patch III is suitable for use in clinical practice pending further studies.

Background: Mycetoma is a chronic, degenerative, and incapacitating infection of the skin and subcutaneous tissue. Aim: This study focuses on developing a kanamycin-based auxiliary system intended to be used in the treatment of mycetoma caused by Actinomadura madurae. Methods: Transdermal patches (with two different formulations: one with free kanamycin [K] and the other one with kanamycin adsorbed in silica [K-SG]) and an emulgel were developed. Both patches were prepared by the casting-evaporation technique. To characterize them, differential scanning calorimetry, bioadhesion, post-moisture detachment, strength and rupture distance, gas exchange, water uptake, and dissolution studies were carried out. The emulgel (containing 0.57% of kanamycin) was prepared from an oil-in-water emulsion, which was then incorporated to a gel. Results: the patches with the best characteristics contained 22.9% of silica and 14.6% of kanamycin. Dissolution studies indicated that 8.8% of kanamycin released from K and 3.2% from K-SG at 24h. The emulgel containing 0.57% of kanamycin showed good technological characteristics for its application to the skin (viscosity, 44.9 ± 1.4 poises; pH, 6.9 ± 0.4; and penetrability, 52.7 ± 5.1). Conclusions: The optimal patches were those containing 15.9% of freely dispersed kanamycin (K) and 14.6% of kanamycin adsorbed in silica (K-SG), which corresponds to the batch 2-0.8. The assessments performed to both pharmaceutical forms (patches and emulgel) show that they have the adequate technological characteristics for being used as an auxiliary in the treatment of actinomycetoma caused by A. madurae.

The purpose of this work was to propose a drug delivery system based on a biodegradable porous membrane, whose surface is covered by a nanoparticle film, thus achieving a controlled drug release rate. Furthermore, due to the fact that the assembly of the system is performed in aqueous medium, contact with organic solvents is avoided. The method is performed in two steps: (i) preparation of biodegradable porous membranes (by a solvent casting and particulate leaching technique) and biodegradable nanoparticles (by the emulsification-diffusion method), extensively eliminating the solvent in both of them; (ii) infiltration into membranes of an aqueous solution of a model drug (carbamazepine) and a nanoparticle dispersion. In both cases, poly(DL-lactic-co-glycolic acid) (PLGA 50:50) was used as a biodegradable polymer. Carbamazepine adsorbed onto biodegradable porous membranes shows an immediate release behavior (95% released in

Cigarette smoking is the primary cause of lung cancer, cardiovascular diseases, reproductive disorders and delayed wound healing all over the world; as such, the goals of smoking cessation are both to reduce health risks and to improve quality of life. The development of novel and more effective medications for smoking cessation is crucial in the treatment of nicotine dependence. Currently, first-line smoking cessation therapies include nicotine replacement products and bupropion. The partial nicotinic receptor agonist, varenicline, has recently been approved by the FDA for smoking cessation. A newer product seeking approval by the FDA is nicotine vaccine. Clonidine and nortriptyline have demonstrated some efficacy, but side effects may limit their use to second-line treatment products. Other therapeutic drugs that are under development include rimonabant, mecamylamine, monoamine oxidase inhibitors, and dopamine D3 receptor antagonists. In order to increase the range of drugs available for transdermal delivery a number of chemical and physical enhancement techniques have been developed in an attempt to compromise skin barrier function in a reversible manner without concomitant skin irritation. The controlled delivery afforded by constant current iontophoresis, which involves the application of a small electrical potential sets it apart from other technologies. The amount of compound delivered is directly proportional to the quantity of charge passed; it depends on the applied current, the duration of current application and the area of the skin surface in contact with the active electrode compartment. For these reasons, iontophoresis will provide smokers with an additional option to assist in achieving smoking cessation.

Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Acetonitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 x 100 mm, 1.7 μm (Waters®). The mobile phase consisted in 5 mM ammonium formate and methanol:acetonitrile (40:48:12 v/v/v) at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z1+ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclophosphamide (internal standard). This method was linear within a 100–10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females), with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 μmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7–19.7 μmol/L. The median at 12 hours was 19.5 μmol/L (Q25 14.4–Q75 29.0) and 3.8 μmol/L (Q25 1.5–Q75 9.9) at 24 hours, p

Buffer rods can be used to perform non-destructive and on-line analysis of food and beverage products. These rods, usually solid cylinders, can be long and heavy for certain applications. In this paper, a resizing analytic procedure is described. Buffer rods designed following this new procedure can be several times shorter than the conventionally designed ones, optimising thus their weight and cost. The signal to noise ratio (SNR) of the resized buffers is also studied in order to determine their practical usability. To this effect, simulations and experiments are conducted using metal and plastic buffer rod materials appropriate for food and beverage testing such as aluminium and polyethylene.