Compliance of commercial bleaches and stability of 1 g/L-dilutions using different sources of drinking water / Conformidad de lavandinas comerciales y estabilidad de diluciones 1g/L utilizando diferentes fuentes de agua potable

Introducción y Objetivos: En el contexto de COVID-19, la Organización Mundial de la Salud recomienda el uso de soluciones de hipoclorito de sodio 1 g/L, como una concentración capaz de inactivar el SARS-CoV-2 y la gran mayoría de patógenos presentes en el entorno sanitario. En consecuencia, hay un renovado interés en realizar estudios de estabilidad de estas disoluciones. El objetivo de este trabajo es verificar la concentración de cloro activo en varias marcas comerciales de hipoclorito de sodio y proponer una fecha límite de uso para soluciones de 1 g/L, obtenidas por dilución con agua potable proveniente de diferentes fuentes.Métodos: La concentración de cloro activo de preparaciones comerciales con concentración nominal entre 25-60 g/L fue valorada por titulación iodométrica. A partir de una de las marcas comerciales se prepararon diluciones de 1 g/L usando agua proveniente de diferentes plantas potabilizadoras en Córdoba, Argentina. Las disoluciones se almacenaron a temperatura ambiente, tanto expuestas como protegidas de la luz y fueron posteriormente tituladas a intervalos de tiempo preestablecidos. La fecha límite de uso se alcanzó cuando la concentración de cloro activo cayó por debajo del 90 % de la inicial.Resultados: La concentración de cloro activo en las soluciones comerciales estuvo dentro de los valores establecidos por la normativa vigente. Las diluciones protegidas de la luz mostraron una disminución menor al 10 % en la concentración de cloro activo durante los primeros 10 días de ensayo. (AU)

Introduction and objectives: In the context of COVID-19, the World Health Organization has recommended the use of extemporaneously prepared bleach solutions of 1 g/L, as a conservative concentration able to inactivate SARS-CoV-2 and the vast majority of other pathogens that may be present in the healthcare setting. Consequently, there is a renewed interest in conducting stability studies of these solutions. The goal of this work was to verify the available chlorine concentration in several bleach solutions trademarks and to propose a beyond use date for 1 g/L bleach solutions, obtained after dilution with drinking water from different sources.Methods: Bleach trademarks, with nominal concentrations between 25-60 g/L, were subjected to iodometric titration to determine the available chlorine concentration. One trademark was used to prepare 1 g/L dilutions using water from different purification plants in Córdoba, Argentina. The samples were stored at room-temperature, both exposed or protected from light. The available chlorine concentration was determined by titration at preestablished time intervals. The beyond use date was reached when the available chlorine concentration dropped below 90 % of its initial.Results: The concentration of active chlorine in the different trademark bleaches was within the values established by current regulations. Diluted solutions protected from light showed a decrease of less than 10 % in active chlorine concentration during the first 10 days of assay. However, one sample exceeded the acceptance limit after 14 days. In contrast, in the samples exposed to light, the concentration of active chlorine dropped to 96.4 % at 24 hours and 79.3 % after 48 hours. (AU)

Fluorescent Multifunctional Organic Nanoparticles for Drug Delivery and Bioimaging: A Tutorial Review.

Fluorescent organic nanoparticles (FONs) are a large family of nanostructures constituted by organic components that emit light in different spectral regions upon excitation, due to the presence of organic fluorophores. FONs are of great interest for numerous biological and medical applications, due to their high tunability in terms of composition, morphology, surface functionalization, and optical properties. Multifunctional FONs combine several functionalities in a single nanostructure (emission of light, carriers for drug-delivery, functionalization with targeting ligands, etc.), opening the possibility of using the same nanoparticle for diagnosis and therapy. The preparation, characterization, and application of these multifunctional FONs require a multidisciplinary approach. In this review, we present FONs following a tutorial approach, with the aim of providing a general overview of the different aspects of the design, preparation, and characterization of FONs. The review encompasses the most common FONs developed to date, the description of the most important features of fluorophores that determine the optical properties of FONs, an overview of the preparation methods and of the optical characterization techniques, and the description of the theoretical approaches that are currently adopted for modeling FONs. The last part of the review is devoted to a non-exhaustive selection of some recent biomedical applications of FONs.

Ionic complexation improves wound healing in deep second-degree burns and reduces in-vitro ciprofloxacin cytotoxicity in fibroblasts.

The development of new treatments capable of controlling infections and pain related to burns continues to be a challenge. Antimicrobials are necessary tools, but these can be cytotoxic for regenerating cells. In this study, antibiotic-anesthetic (AA) smart systems obtained by ionic complexation of polyelectrolytes with ciprofloxacin and lidocaine were obtained as films and hydrogels. Ionic complexation with sodium alginate and hyaluronate decreased cytotoxicity of ciprofloxacin above 70% in a primary culture of isolated fibroblasts (p < 0.05). In addition, the relative levels of the proteins involved in cell migration, integrin ß1 and p-FAK, increased above 1.5 times (p < 0.05) with no significant differences in cell mobility. Evaluation of the systems in a deep second-degree burn model revealed that reepithelization rate was AA-films = AA-hydrogels > control films > no treated > reference cream (silver sulfadiazine cream). In addition, appendage conservation and complete dermis organization were achieved in AA-films and AA-hydrogels. Encouragingly, both the films and the hydrogels showed a significantly superior performance compared to the reference treatment. This work highlights the great potential of this smart system as an attractive dressing for burns, which surpasses currently available treatments.

Sustained dual release of ciprofloxacin and lidocaine from ionic exchange responding film based on alginate and hyaluronate for wound healing.

This study presents a new antibiotic-anesthetic film (AA-film) based on natural polyelectrolytes ionically complexed with lidocaine and ciprofloxacin to manage pain associated with infected wounds. The rational selection of the components resulted in the AA-films being transparent, compatible with wound skin pH and highly water vapor permeable. The drug release properties evaluated in saline solution and water revealed an ionic exchange mechanism for the release of both drugs and showed that ciprofloxacin acts as a cross-linker, as was confirmed by rheological evaluation. The in vitro antimicrobial efficacy against S. aureus and P. aeruginosa was demonstrated. Furthermore, AA-films exhibit a high fluid absorption capacity and act as a physical barrier for microorganisms. This work highlights the great potential of this smart system as an attractive dressing for skin wounds, surpassing currently available treatments.

Anti-tuberculosis site-specific oral delivery system that enhances rifampicin bioavailability in a fixed-dose combination with isoniazid.

The in vivo release segregation of rifampicin (RIF) and isoniazid (INH) has been proposed as a strategy to avoid RIF acid degradation, which is known as one of the main factors for reduced RIF bioavailability and can result in drug-resistant tuberculosis. So far, this strategy has been scarcely explored. The aims of this study were to investigate the stability and bioavailability of RIF after combination of a very fast release matrix of RIF with a sustained delivery system of INH. A series of INH-alginic acid complexes (AA-INH) was obtained and characterized. Independent and sequential release profile of AA-INH at biorrelevant media of pH 1.20 and 6.80 was explored. In addition, AA-INH was combined with a RIF-carboxymethylcellulose very fast release complex (CMC-RIF) obtained previously and subjected to acid dissolution assays to evaluate RIF acid stability and determine RIF and INH dissolution efficiencies. Finally, a pharmacokinetic study in dogs was carried out. The AA-INH was easily obtained in solid-state. Their characterization revealed its ionic nature, with a loading capacity of around 30%. The dissolution efficiencies (15 min) confirmed release segregation in acid media with 7.8 and 65.6% for AA-INH and CMC-RIF, respectively. INH release rate from the AA-INH system was slow in acid media and increased in simulated intestinal media. The complete release of INH was achieved after 2 h in simulated intestinal media in the sequential release experiments. The acid degradation of RIF was significantly reduced (36.7%) when both systems were combined and oral administration to dogs revealed a 42% increase in RIF bioavailability. In conclusion, CMC-RIF and AA-INH may be useful for the formulation of a site-specific solid dosage form to overcome some of the main obstacles in tuberculosis treatment. Graphical abstract.

Compliance of commercial bleaches and stability of 1 g/L-dilutions using different sources of drinking water / Conformidad de lavandinas comerciales y estabilidad de diluciones 1g/L utilizando diferentes fuentes de agua potable

INTRODUCTION AND OBJECTIVES: In the context of COVID-19, the World Health Organization has recommended the use of extemporaneously prepared bleach solutions of 1 g/L, as a conservative concentration able to inactivate SARS-CoV-2 and the vast majority of other pathogens that may be present in the healthcare setting. Consequently, there is a renewed interest in conducting stability studies of these solutions. The goal of this work was to verify the available chlorine concentration in several bleach solutions trademarks and to propose a beyond use date for 1 g/L bleach solutions, obtained after dilution with drinking water from different sources. METHODS: Bleach trademarks, with nominal concentrations between 25-60 g/L, were subjected to iodometric titration to determine the available chlorine concentration. One trademark was used to prepare 1 g/L dilutions using water from different purification plants in Córdoba, Argentina. The samples were stored at room-temperature, both exposed or protected from light. The available chlorine concentration was determined by titration at preestablished time intervals. The beyond use date was reached when the available chlorine concentration dropped below 90 % of its initial. RESULTS: The concentration of active chlorine in the different trademark bleaches was within the values established by current regulations. Diluted solutions protected from light showed a decrease of less than 10 % in active chlorine concentration during the first 10 days of assay. However, one sample exceeded the acceptance limit after 14 days. In contrast, in the samples exposed to light, the concentration of active chlorine dropped to 96.4 % at 24 hours and 79.3 % after 48 hours. No differences related to drinking water sources were observed. CONCLUSIONS: Compliance of the nominal available chlorine concentration in trademark bleach solutions was confirmed. Regardless the water source used for dilution, 1 g/L bleach solutions were stable for 10 days when stored at room temperature and protected from light. Instead, solutions exposed to light maintain their available chlorine concentration for only 24 hours

INTRODUCCIÓN Y OBJETIVOS: En el contexto de COVID-19, la Organización Mundial de la Salud recomienda el uso de soluciones de hipoclorito de sodio 1 g/L, como una concentración capaz de inactivar el SARS-CoV-2 y la gran mayoría de patógenos presentes en el entorno sanitario. En consecuencia, hay un renovado interés en realizar estudios de estabilidad de estas disoluciones. El objetivo de este trabajo es verificar la concentración de cloro activo en varias marcas comerciales de hipoclorito de sodio y proponer una fecha límite de uso para soluciones de 1 g/L, obtenidas por dilución con agua potable proveniente de diferentes fuentes. MÉTODOS: La concentración de cloro activo de preparaciones comerciales con concentración nominal entre 25-60 g/L fue valorada por titulación iodométrica. A partir de una de las marcas comerciales se prepararon diluciones de 1 g/L usando agua proveniente de diferentes plantas potabilizadoras en Córdoba, Argentina. Las disoluciones se almacenaron a temperatura ambiente, tanto expuestas como protegidas de la luz y fueron posteriormente tituladas a intervalos de tiempo preestablecidos. La fecha límite de uso se alcanzó cuando la concentración de cloro activo cayó por debajo del 90 % de la inicial. RESULTADOS: La concentración de cloro activo en las soluciones comerciales estuvo dentro de los valores establecidos por la normativa vigente. Las diluciones protegidas de la luz mostraron una disminución menor al 10 % en la concentración de cloro activo durante los primeros 10 días de ensayo. Sin embargo, una muestra superó el límite de aceptación luego de 14 días. En contraste, en las muestras expuestas a la luz, la concentración de cloro activo cayó a 96.4 % a las 24 horas y 79.3 % después de 48 horas. No se observaron diferencias relacionadas con las fuentes de agua potable. CONCLUSIONES: se confirmó la concentración nominal de cloro activo en todas las marcas comerciales evaluadas. Independientemente de la fuente de agua potable utilizada para la dilución, las soluciones de 1 g/L fueron estables durante 10 días cuando se almacenaron a temperatura ambiente y protegidas de la luz. En contraste, las soluciones expuestas a la luz mantienen la concentración de cloro activo durante solo 24 horas

Development of a Carrier-Free Dry Powder Ofloxacin Formulation With Enhanced Aerosolization Properties.

Tuberculosis (TB) is a serious infectious disease that affects more than new 10 million patients each year. Many of these cases are resistant to first-line drugs so second-line ones, like fluoroquinolones, need to be incorporated into the therapeutic. Ofloxacin (OF) is a fluoroquinolone which demonstrates high antibiotic activity against the bacteria that causes TB (M. tuberculosis). In this work, ionic complexes, composed by hyaluronic acid (HA) and OF, with different neutralization degrees, were prepared and processed by spray drying (SD) to obtain powders for inhalatory administration. Combining a formulation with high neutralization degree, high SD atomization air flowrate and the use of a high-performance collection cyclone, very good process yields were obtained. Carrier-free formulations with a loading of 0.39-0.46 gOF/gpowder showed excellent emitted, fine particle, and respirable fractions for capsule loadings of 25 and 100 mg. The ionic complexes demonstrated higher mucoadhesion than pure OF and HA. The best formulation did not affect CALU-3 cell viability up to a dose 6.5 times higher than the MIC90 reported to treat multi-drug resistant TB.

Preclinical pharmacokinetics of benznidazole-loaded interpolyelectrolyte complex-based delivery systems.

Benznidazole (BZ), first-line drug for Chagas treatment, is available as immediate-release tablets. High frequency of administration, long-term therapy, and side effects of BZ conspire against treatment adherence, and negatively impact in therapeutic success. We have developed BZ-loaded interpolyelectrolyte complexes (IPECs) composed of polymethacrylates (EE-EL-BZ) or polysaccharides (Ch-AA-BZ) for controlled BZ release. This work aimed to evaluate their preclinical pharmacokinetics compared to Abarax® (reference treatment) and to correlate them with the in vitro BZ release. A randomization schedule with a 3 × 2 cross-over design was used. Each healthy dog received a single oral dose of 100 mg of BZ from EE-EL-BZ, Ch-AA-BZ or Abarax®. BZ quantification was performed in plasma by a validated HPLC-UV method. Moreover, in silico simulations using the pharmacokinetic software PK Solutions 2.0™ were calculated for the multiple-dose administration at two dose regimens: 100 mg of BZ administered every 12 and 24 h. Also, the relationship between in vitro dissolution and in vivo plasma BZ concentration profiles in a single step was model for IVIVC analysis. BZ was rapidly absorbed from all formulations. The Cmax value for Ch-AA-BZ was 32% higher than reference (p < 0.05) and an earlier Tmax (4.2 h) was observed as compared to EE-EL-BZ (6.0 h). For both IPECs, the Tmax values were higher (p < 0.05) and the areas under the curve were 25% greater than those of Abarax® (p < 0.01). Despite these variations in pharmacokinetics parameters, simulations of once or twice daily dosing showed that all formulations reached a steady-state range concentration above of the minimum therapeutic dose while avoiding high BZ concentrations related to increased side effects. A linear level A IVIVC model was established using plasma concentration profiles and dissolved data obtained. Thus, BZ-loaded IPECs prolonged drug release and formulated as capsules showed improved in vivo performance, in terms of bioavailability and Tmax values, which were significantly higher compared to Abarax®. These BZ carrier systems would be useful for oral administration in the treatment of Chagas disease.

Ciprofloxacin-lidocaine-based hydrogel: development, characterization, and in vivo evaluation in a second-degree burn model.

The purpose of this work was to develop an effective carbomer hydrogel to be used to treat second-degree burns that combined ciprofloxacin and lidocaine (CbCipLid hydrogel). Its antibiotic and anesthetic efficacy and the physical and chemical properties of the CbCipLid hydrogel (release rate and kinetics, rheology, appearance, and drug content) were evaluated both before and after a sterilization cycle and also after 6 months of storage. For the in vivo studies, second-degree burns were developed in a rat model. Animals were divided into three groups: CbCipLid hydrogel, silver sulfadiazine cream (reference), and carbomer hydrogel (as control). The treatments were applied daily for 21 days, and the healing was monitored by macroscopic observation and histologic evaluation. The anesthetic effect was evaluated through the corneal touch threshold in a rabbit eye model. The CbCipLid hydrogel obtained is transparent and allows the loading of ciprofloxacin above its solubility at a neutral pH, with a rheology which is convenient for topical administration. Its physical and chemical properties remained unchanged after sterilization and for at least six additional months. Both ciprofloxacin and lidocaine are reversibly released from the CbCipLid hydrogel with a kinetics fitting the Higuchi model. The presence of a biologic-like fluid increased the rate of drug delivery through an ionic exchange mechanism. Treatment with the CbCipLid hydrogel decreased the wound-healing period, compared with the reference, and was associated with a greater number of fibroblasts and a faster rate of epithelialization and dermis reconstruction. These differences were assigned to the moist environment provided by the hydrogel and also to the presence of a therapeutic concentration of ciprofloxacin. Moreover, CbCipLid hydrogel provides an immediate anesthetic effect, which is significantly more intense than that of the reference. Based on these results, it is believed that the CbCipLid hydrogel could be a potential candidate in the prophylaxis/treatment of second-degree burns.

Urinary excretion of ciprofloxacin after administration of extended release tablets in healthy volunteers. Swellable drug-polyelectrolyte matrix versus bilayer tablets.

This paper builds on a previous paper in which new ciprofloxacin extended-release tablets were developed based on a ciprofloxacin-based swellable drug polyelectrolyte matrix (SDPM-CIP). The matrix contains a molecular dispersion of ciprofloxacin ionically bonded to the acidic groups of carbomer, forming the polyelectrolyte-drug complex CB-CIP. This formulation showed that the release profile of the ciprofloxacin bilayer tablets currently commercialised can be achieved with a simpler strategy. Thus, since ciprofloxacin urine concentrations are associated with the clinical cure of urinary tract infections, the goal of this work was to compare the urinary excretion of SDPM-CIP tablets with those of the CIPRO XR® bilayer tablets. A batch of SDPM-CIP tablets was manufactured by the wet granulation method and the CB-CIP ionic complex was obtained in situ. Fasted healthy volunteers received a single oral dose of 500 mg ciprofloxacin of either formulation in a randomised crossover study. Urinary concentrations were assessed by HPLC at intervals up to 36 h. Pharmacokinetic parameters (rate of urinary excretion, maximum urine excretion rate, tmax, area under the curve, amount and percentage of the ciprofloxacin dose excreted in urine) showed no statistical differences between both formulations at any of the time intervals of collection. The processing conditions to obtain SDPM-CIP tablets are easy to scale up since they involve technology currently employed in the pharmaceutical industry and the process is less challenging to implement. In addition, SDPM-CIP tablets met pharmacopoeial quality specifications.

[Bioavailability of phenolic compounds and redox state of murine liver and kidney as sex-dependent responses to phytoextracts.]

BACKGROUND: Plant extracts can be obtained to carry bioactive compounds, useful for prevention and treatment of different illnesses. This also supports the intake of teas as functional beverages. Nonetheless, it is incompletely known whether these extracts can act as effective sources and vehicles de phenolic compounds (phenolics/polyphenols) to reach their targets. OBJECTIVE: To establish whether phytoextract ingestion modified in a sex-dependent manner the phenolic bioavailability and redox response in liver and kidney. METHOD: BALB/C mice ingested for a month 100 mg/Kg/d of extracts (tea-like) from Aspidosperma quebracho-blanco (AQB), Lantana grisebachii (LG) or Ilex paraguariensis (IP). Then, phenolics, peroxides and nitrites were analyzed by spectrophotometry. Also, phenolic permeation from digested and undigested extracts was evaluated in vitro with a rat jejunum-based assay. RESULTS: Phenolic permeation depended on extract digestion. In males, IP showed a special time course of hepatic phenolics, whereas all extracts decreased renal phenolics at 15 days. Extracts induced hepatic lipoperoxides at 15 days. LG reduced renal hydroperoxides at 15 days and hepatic nitrites at 30 days, whereas AQB and IP reduced renal lipoperoxides and nitrites at 30 days. In females, extracts reduced hydroperoxides, with LG and AQB also reducing lipoperoxides. IP increased renal lipoperoxides at 30 days. CONCLUSION: IP was a relevant phenolic source. Sex-dependent responses were found in all variables, which should be considered to prevent misleading generalizations in phytodrug bioprospecting.

Importancia de los sistemas de información en programas de salud pública: bases de datos de pacientes diabéticos / Importance of the information systems in public health programs: diabetic patients databases

Objetivos: Describir las características de la población de pacientes diabéticos atendida en el subsector público de salud de la ciudad de Alta Gracia. Analizar el uso de la cantidad de dispensaciones mensuales como indicador de adherencia al tratamiento, comparando resultados entre establecimientos sanitarios. Valorar la coordinación de efectores públicos en la atención de pacientes. Materiales y métodos: Diseño: estudio observacional, descriptivo-analítico. Lugar: Hospital Arturo Umberto Illia (HAUI) y Dirección de Salud Pública (DSP). Alta Gracia (Provincia de Córdoba, Argentina). Población: Pacientes diabéticos pertenecientes a programas de salud de efectores públicos. Mediciones principales: Variables demográficas y epidemiológicas, cantidad de dispensaciones mensuales, adherencia global porcentual y coordinación de efectores. Resultados: Del total de pacientes diabéticos (n=540): 52% se atendían en el HAUI, 39% en la DSP y 9% en ambos centros; 55% eran mujeres y la edad promedio fue de 56 años; 81% correspondían a Diabetes Mellitus (DM) tipo 2, 1% a DM tipo 2 insulino-requirentes y 17% a DM tipo 1; la media general de cantidad de dispensaciones mensuales por paciente fue de 4,9 en 12 meses. Se observó falta de personal capacitado para gestión de información en ambos centros. Conclusiones: Las bases de datos permitieron conocer algunas características demográficas de la población diabética de Alta Gracia atendidas en el sector público. La frecuencia de dispensaciones durante los 12 meses pudo emplearse como indicador de adherencia al tratamiento. Se confirmó la exigua coordinación entre niveles de atención y jurisdicciones (provincial y municipal). Generar y mantener sistemas de información resulta necesario para tomar decisiones (AU)

Aims: To describe the characteristics of diabetic patients’ population attended in the public health sector of Alta Gracia city. To analyze the use of amount of monthly dispensations as indicator of adherence to treatment, by comparing the results between settings. To assess the coordination of public facilities for patients attention. Materials and methods: Design: observational descriptive-analytical study. Settings: Hospital Arturo Umberto Illia (HAUI) and Dirección de Salud Pública (DSP). Alta Gracia (province of Córdoba, Argentina). Subjects: diabetic patients belonging to health programs at public facilities. Main measures: demographic and epidemiological variables, amount of monthly dispensations, percentage of global adherence and coordination of settings. Results: From diabetic patients’ total (n=540): 52% were attended at HAUI, 39% at DSP, and 9% at both settings; 55% were female, and the average age was about 56 years old; 81% were type 2 Diabetes Mellitus (DM), 1% type 2 insulin-requiring DM, and 17% type 1 DM; the general mean of amount of monthly dispensations by patient was 4.9 in 12 months. Lack of trained personnel for information managing in both facilities was observed. Conclusions: The databases allowed knowing some demographic characteristics of diabetic population attended in the public sector of Alta Gracia. The dispensing frequency during 12 months was able to be used as an adherence to treatment indicator. The scarce coordination between care levels and jurisdictions (provincial and municipal) were confirmed. For decision making it is necessary to generate and maintain information systems (AU)

Equilibrium and release properties of hyaluronic acid-drug complexes.

With the aim to provide more rational basis about the potentiality of hyaluronic acid (or hyaluronan) as drug carrier a set of ionic complexes of its acid form (HA) and its sodium salt (NaHA) with three model drugs (D) (atenolol, propranolol and lidocaine) were prepared. Besides NaHA subjected to hyalurodinase depolimerization (NaHA(d)) was also used. Transparent dispersions were obtained. They exhibited negative electrokinetic potential and a high degree of counterionic condensation with affinity constants (log Kcc) in the range of 5.8-6.1 for propranolol complexes (pK(a) 9.45) and 4.0-4.6 for lidocaine ones (pK(a) 7.92). Delivery rates of D from the complexes were measured in a Franz-type bicompartimental device. Loaded D were slowly released from the three types of complexes, even when a neutral salt was added to the dispersion placed in the donor compartment, revealing the high affinity between the protonated drugs and the ionisable groups of the polymer. Complex dispersions based on HA or on NaHA(d) exhibited lower viscosity than those of NaHA but their complexing ability remained unaltered. The results reported on equilibrium and release properties of Hyaluronan-model D complexes contribute to expand the use of HA and NaHA as drug carriers for different routes of administration.

Systemic exposure, tissue distribution, and disease evolution of a high solubility ciprofloxacin-aluminum complex in a murine model of septicemia induced by salmonella enterica serotype Enteritidis.

A new pharmaceutical derivative obtained by stoichiometric complexation of ciprofloxacin (CIP) with aluminum (CIP-complex) has been investigated and reported in this study. Such product has high solubility in the gastrointestinal pH range and was successful in the development of optimized formulations while maintaining its antimicrobial potency. The systemic exposure, tissue distribution, and the disease evolution after given CIP-complex were assessed. The systemic exposure and distribution in intestines, lungs, and kidneys after a single intragastric administration of CIP-complex and CIP given alone, used as reference, were performed in Balb-C mice at a dose of 5 mg CIP/kg. For the assessment of the disease evolution assay, mice were infected with a virulent strain of Salmonella enterica serotype Enteritidis and treated intragastrically once or twice daily during 5 consecutive days with solutions of CIP-complex or the reference. Clinical follow up and survival was measured during 15 days post inoculation and health state was scored during this period from 0 to 5. CIP-complex showed a 32% increase in C(max), an earlier T(max), and a smaller AUC(0-12) than the reference. Maximum tissue concentrations (0.5-1 h) were significantly higher in CIP-complex (447% in intestine, 93% in kidney, and 44% in lungs). In the infection model used in this study, survival in CIP-complex versus CIP groups was 40% versus 20% (twice-daily administration) and 30% versus 0% (once-daily administration). Health state of the survivors of CIP-complex group (5/5) was higher than CIP group (3/5). The greater effectiveness of CIP-complex is attributed to the higher levels of CIP in the intestine. Our results supported the fact that CIP-complex is a promising candidate to develop dose-efficient formulations of CIP for oral administration.

Farmacoepidemiología aplicada a programas públicos para pacientes diabéticos em Altaracia (Córdoba, Argentina) / Pharmacoepidemiology applied to public programs for diabetic patients in Alta Gracia (Córdoba, Argentina)

La Diabetes Mellitus es una enfermedad crónicarelacionada con hiperglucemia y la finalidad del tratamientoes prevenir y reducir las complicaciones, responsables de másdel 70% de muertes. Se analizaron programas de salud con provisión de medicamentos en instituciones públicas de la ciudad de Alta Gracia: Hospital Arturo Umberto Illia (HAUI),dependiente del Ministerio de Salud (Provincia de Córdoba) y 12 dispensarios dependientes de la Dirección de Salud Pública (DSP), Municipalidad de Alta Gracia.Se identificaron 540 pacientes en la base de datos unificada y 49 se hallaron en ambas instituciones. Losconsumos de medicamentos, en DDD por cada 100 pacientes bajo programa/día, fueron: para Glibenclamida 25,2 en HAUIy 24,6 en DSP; para Metformina 17,6 en HAUI y 13,1 en DSP; para Insulina 59,0 en HAUI. La información obtenida desde Farmacia permitiódesarrollar una base de datos de pacientes diabéticos y unestudio de utilización de medicamentos.

Diabetes Mellitus is a chronic disease related to hyperglycaemia, and its treatment purposes are preventing and reducing the complications which cause more than 70% of deaths. Health programs with drug supply at public health facilities in Alta Gracia Citywere analized: Hospital Arturo Umberto Illia (HAUI), depending on the Health Ministry of the Province of Córdoba, and 12 dispensaries, depending on the Dirección de SaludPública (DSP) of the Municipality of Alta Gracia. A total of 540 patients were identified in the merged data base and 49 were found inboth settings. Drug consumptions, expressed in DDD per 100 patient under program by day, were: 25.2 in HAUI and 24.6 in DSP for glibenclamide; 17.6 in HAUI and 13.1 in DSP for Metformin; 59.0 in HAUI for Insulin. The information obtained from the Pharmacy Services let the development of a diabetic patient data base and a consumption drug utilization study.

Intercambiabilidad entre medicamentos: clasificación de fármacos según nivel de equivalencia requerido

Los ensayos de BE in vivo han sido aceptados por los últimos 25 años como el método estándar para aprobar cambios mayores en los procesos de elaboración y para garantizar la eficacia de medicamentos genéricos en todo el mundo. En el último decenio se ha propuesto un nuevo criterio aplicable a un gran número de productos que se basa en los procesos fundamentales que controlan la magnitud y velocidad de absorción de fármacos: el Sistema de Clasificación Biofarmacéutica (SCB). Este sistema estratifica los fármacos en 4 grandes grupos de acuerdo a su permeabilidad y la solubilidad relativa a la dosis y es aplicable a formas farmacéuticas sólidas de liberación inmediata y acción sistémica La mayor aplicación del SCB es proveer criterios para la bioexención de productos multifuente. La ANMAT reconoce la existencia del SCB y las posibilidades de bioexcenciones por lo que estos avances serían extrapolables a nuestra realidad. El objetivo general de este proyecto es contribuir a la problemática planteada generando información vinculable con la intercambiabilidad entre medicamentos.

Solution and solid state properties of a set of procaine and procainamide derivatives.

A set of potential Class III antiarrhythmic agents of structure p-HOOC-R-CO-NH-C(6)H(4)-CO-X-C(2)H(5)-N(C(2)H(5))(2) were isolated as crystalline solids of the amide and ester derivatives, I: succinylprocainamide (X=-NH-, R=-C(2)H(4)-); II: succinylprocaine (X=-O-, R=-C(2)H(4)-); III: maleylprocainamide (X=-NH-, R=-C(2)H(2)-) and IV: maleylprocaine (X=-O-, R=-C(2)H(2)-). Although compounds I-IV exhibit similar solution properties (i.e. acid-base speciation, with zwitterionic (+-) to neutral (00) form ratios higher than 10(4)), aqueous solubility of -NH- derivatives is significantly higher than that of -O- derivatives and also, solvent effects on solubility (i.e. the change of water by ethanol) is clearly different in both series. Solution and solid-state properties of I-IV were characterized to account for the observed differences. Results indicate that procainamide derivatives I and III crystallizes as (+-)(s) but procaine derivatives II and IV as (00)(s). Besides, I is anhydrous but II-IV are hydrates. Aqueous solubility and solvent effect on solubility are controlled by the intrinsic solubility of the species (+-) in I and III and (00) in II and IV. The rise of hydrophilicity of species (00) due to the structural change from -O- to -NH- would determine the change in the structure of the precipitating crystals from (00)(s) to (+-)(s). Solid structure (zwitterionic or neutral), as well as composition (anhydrous or hydrated) may be recognized as the main factors in determining the rank of aqueous solubility of the set: (+-)>(+-.H(2)O)>(00.H(2)O).

Intercambiabilidad entre medicamentos: clasificación de fármacos según nivel de equivalencia requerido

Los ensayos de BE in vivo han sido aceptados por los últimos 25 años como el método estándar para aprobar cambios mayores en los procesos de elaboración y para garantizar la eficacia de medicamentos genéricos en todo el mundo. En el último decenio se ha propuesto un nuevo criterio aplicable a un gran número de productos que se basa en los procesos fundamentales que controlan la magnitud y velocidad de absorción de fármacos: el Sistema de Clasificación Biofarmacéutica (SCB). Este sistema estratifica los fármacos en 4 grandes grupos de acuerdo a su permeabilidad y la solubilidad relativa a la dosis y es aplicable a formas farmacéuticas sólidas de liberación inmediata y acción sistémica La mayor aplicación del SCB es proveer criterios para la bioexención de productos multifuente. La ANMAT reconoce la existencia del SCB y las posibilidades de bioexcenciones por lo que estos avances serían extrapolables a nuestra realidad. El objetivo general de este proyecto es contribuir a la problemática planteada generando información vinculable con la intercambiabilidad entre medicamentos.

Intercambiabilidad entre medicamentos: clasificación de fármacos según nivel de equivalencia requerido

Los ensayos de BE in vivo han sido aceptados por los últimos 25 años como el método estándar para aprobar cambios mayores en los procesos de elaboración y para garantizar la eficacia de medicamentos genéricos en todo el mundo. En el último decenio se ha propuesto un nuevo criterio aplicable a un gran número de productos que se basa en los procesos fundamentales que controlan la magnitud y velocidad de absorción de fármacos: el Sistema de Clasificación Biofarmacéutica (SCB). Este sistema estratifica los fármacos en 4 grandes grupos de acuerdo a su permeabilidad y la solubilidad relativa a la dosis y es aplicable a formas farmacéuticas sólidas de liberación inmediata y acción sistémica La mayor aplicación del SCB es proveer criterios para la bioexención de productos multifuente. La ANMAT reconoce la existencia del SCB y las posibilidades de bioexcenciones por lo que estos avances serían extrapolables a nuestra realidad. El objetivo general de este proyecto es contribuir a la problemática planteada generando información vinculable con la intercambiabilidad entre medicamentos.