Development, characterization, and in vitro evaluation of tamoxifen microemulsions.

Microemulsions (MEs) were designed by an innovative rational development, characterized, and used to load up to 20 mM of Tamoxifen citrate (TMX). They were made with acceptable and well-characterized excipients for all the routes of administration. Some of their properties, such as nanometric mean size and long stability shelf life, make them interesting drug delivery systems. The results obtained after the in vitro inhibition of estradiol-induced proliferation in MCF-7 breast cancer cells demonstrated a significant effect in cell growth. A decreasing of at least 90% in viable cells was shown after the incubation with MEs containing 20 mM of TMX. Besides, two compositions which loaded 10 mM of drug showed a cytotoxic effect higher than 70%. These results encourage the evaluation of alternative protocols for this drug administration, not only for estrogen receptor (ER) positive tumors, but also for ER negative.

Carvedilol stability in paediatric oral liquid formulations

Objective Two carvedilol aqueous solutions and one carvedilol aqueous suspension for paediatric oral use (1mg/ml) were studied to determine their stability. Method All samples were stored at 4, 25 and 40°C. Carvedilol content of each of the three formulations was tested using high performance liquid chromatography (HPLC). Each sample was analysed in triplicate at 0, 3, 7, 14, 28 and 56 days. Results Carvedilol stayed stable in the acidic aqueous solution at the three different temperatures during the 56 days of the study. In the alkaline solution, carvedilol was stable during 56 days at 25°C, but only 28 days at 4 and 40°C. In the aqueous suspension, carvedilol was stable during 56 days at 4 and 25°C, but only 28 days at 40°C.ConclusionsAll the formulations that were tested can be stored at 25°C for at least 56 days(AU)

Objetivo Se estudió la estabilidad de carvedilol (1mg/ml) en 2 soluciones acuosas y una suspensión acuosa para uso pediátrico. Método Las formulaciones fueron almacenadas a 4, 25 y 40°C. El contenido de carvedilol de cada una de las 3 formulaciones fue analizado por cromatografía líquida de alta eficacia (HPLC). Cada muestra fue analizada por triplicado a tiempos 0, 3, 7, 14, 28 y 56 días. Resultados Carvedilol se mantuvo estable en la solución acuosa de pH ácido durante los 56 días del ensayo a las 3 temperaturas estudiadas. En la solución alcalina fue estable 56 días a 25°C, pero sólo 28 días a 4 y 40°C. En la suspensión acuosa carvedilol fue estable 56 días a 4 y 25°C, y sólo 28 días a 40°C.ConclusionesTodas las formulaciones ensayadas pueden ser conservadas a 25°C al menos por un período de 56 días (AU)

Carvedilol stability in paediatric oral liquid formulations.

OBJECTIVE: Two carvedilol aqueous solutions and one carvedilol aqueous suspension for paediatric oral use (1mg/ml) were studied to determine their stability. METHOD: All samples were stored at 4, 25 and 40°C. Carvedilol content of each of the three formulations was tested using high performance liquid chromatography (HPLC). Each sample was analysed in triplicate at 0, 3, 7, 14, 28 and 56 days. RESULTS: Carvedilol stayed stable in the acidic aqueous solution at the three different temperatures during the 56 days of the study. In the alkaline solution, carvedilol was stable during 56 days at 25°C, but only 28 days at 4 and 40°C. In the aqueous suspension, carvedilol was stable during 56 days at 4 and 25°C, but only 28 days at 40°C. CONCLUSIONS: All the formulations that were tested can be stored at 25°C for at least 56 days.

Emulsiones líquida-cristalinas estabilizadas con estearato de trietanolamina y ácido esteárico: influencia del método de preparación en las propiedades y en la formación de gotas secundarias / Stabilized liquid-crystalline emulsions with triethanolamine stearate and stearic acid: preparation method influence in the properties and formation of secondary droplets

Se desarrolló una metodología que permite obtener emulsiones de vaselina líquida estabilizadas con estearato de trietanolamina y ácido esteárico con características líquida-cristalinas en las que las gotas se agrupan formando gotas secundarias de unos 15 mcrom de diámetro. La formación de estas gotas secundarias, que es una consecuencia de la presencia de cristales líquidos lioptrópicos en las emulsiones, trae como consecuencia una disminución de la viscosidad. El reemplazo de parte de la vaselina líquida de estas emulsiones por otros emolientes de mayor capacidad de penetración dérmica, tales como el miristato de isopropilo y el 2-octil-1-dodecanol, no disminuye las características líquida-cristalinas, lo que permite obtener otras emulsiones más adecuadas para usos farmacéutico y cosmético

It has been developed a methodology which allows obtaining mineral oil emulsions stabilized with triethanolamine stearate and stearic acid with liquid-crystalline characteristics where droplets cluster themselves forming secondary droplets of 15 microm diameter. The formation of the mentioned secondary droplets, which are a consequence of the presence of lyotropic liquid crystals in the emulsions, produces a diminution of the viscosity. The replacement of part of the mineral oil of these emulsions for others emollients with greater dermal penetration capacity, such as isopropyl myristate and 2-octyl-1-dodecanol, does not diminish the liquid-crystalline characteristics, granting the obtainment of more adequate emulsions for pharmaceutical and cosmetic usage

Rifampicina y biodisponibilidad en productos combinados / Rifampicin and bioavailability in combination formulation

La rifampicina (R) es un antibiótico de primera elección en el tratamiento de la tuberculosis (TB) junto a la Isoniazida (H), Pirazinamida (Z) y Etambutol (E). De acuerdo a las últimas estadísticas, la TB aumentó a nivel mundial y entre las causas más citadas figuran: las monoterapias, la aparición de microorganismos resistentes, la carencia de programas efectivos, el incumplimiento en el tratamiento y las dosis erróneas. La Organización Mundial de la Salud (OMS) y la Unión Internacional Contra la Tuberculosis y Enfermedades de Pulmón (IUATLD) declararon a la enfermedad en emergencia mundial y establecieron programas terapéuticos para asegurar el cumplimiento y disminuir los problemas relacionados a la terapia. Sobre esta base, figura en la lista oficial la asociación de los cuatro fármacos de primera línea R, Z, H y E combinados en dosis fijas (FDC) que permiten la administración conjunta de los mismos y, en las dosis correctas. Los productos FDC son recomendados oficialmente por la OMS para el tratamiento de la TB. No obstante existen factores que alteran la biodisponibilidad de la R en estas formulaciones, hecho ampliamente reconocido en publicaciones científicas. El objetivo de este trabajo es estudiar los aspectos más relevantes que alteran la biodisponibilidad de la R en los productos FDC y plantear posibles soluciones al problema

The drug rifampicin (R) is used as a first line antibiotic treatment for tuberculosis (TB), together with Isoniazide (H), Pyrazinamide (Z) and Ethambutol (E). According to recent statistics, there has been an increase in TB on a worldwide scale, with the main causes being: monotherapies, the appearance of resistant microorganisms, the lack of effective preventative programs, non-compliance to treatment and mistaken dosage schedules. The world health organisation (WHO) and the International Union Against Tuberculosis and Lung Diseases(IUTALD) declared a state of emergency with respect to the disease and established programs to increase compliance to therapy and to reduce the incidence of problems arising from such. Along these lines, a list of first line drug therapy treatments were established, which included R, Z, H & E combinations at fixed dosage combinations (FDC), permitting safe combined administrations of the drugs at correct dosage levels. These fixed dose combinations have been officially recommended by the WHO in the treatment of TB. However, as has been widely recognised in numerous scientific publications, in such formulations, there are factors that alter the bioavailability of R. The objective of this work has been to study the most relevant aspects concerning R bioavailability alterations and to consider possible solutions to the problem

Microesferas biodegradables de poli(D, L-láctico) conteniendo progesterona / Biodegradable microspheres of poly(D, L-lactide) containing progesterone

Se obtuvieron microesferas de poli(D,L-láctico) conteniendo progesterona por medio de una emulsión simple aceite en agua empleando una técnica de evaporación de solvente. Se realizó un experimento con un diseño factorial 23 para estudiar el efecto de tres variables independientes (cantidad de principio activo, cantidad de polímero y concentración de alcohol polivinílico) sobre las variables dependientes (encapsulación de principio activo y tamaño de partícula). Las tres variables independientes influyeron significativamente sobre la encapsulación de progesterona. En el caso del tamaño de partícula, las variables que ejercieron una influencia significativa fueron la concentración de alcohol polivinílico y la cantidad de polímero. Los estudios de liberación in vitro han mostrado que de acuerdo al tamaño de partícula se pueden obtener formulaciones que logran liberar progesterona en pocos días u obtener una liberación sostenida durante 28 días. El estado físico del fármaco se investigó por calorimetría diferencial de barrido. Los estudios muestran que existe una interacción fisicoquímica entre la progesterona y el polímero

Microspheres of poly(D,L-lactide) containing progesterone were prepared by the solvent evaporation method using a simple oil water emulsion. 23 factorial design was used to determine the effect of three independent variables (amount of drug, amount of polymer and concentration of polyvinyl alcohol) over the dependent variables (drug content and particle size). The three independent variables influenced significantly over the percentage drug encapsulated. On the other hand, in the particle size case, the variables which produced a significantly influence were the polyvinyl alcohol concentration and the amount of polymer. The in vitro release studies have shown that according to the particle size, it can be obtained formulations which are able to release progesterone in a few days or a sustained release among 28 days. The physical state of drug has been examined by differential scanning calorimetric. The studies indicate that exists a physicochemical interaction between the progesterone and the polymer

Stability study of lipoic acid in the presence of vitamins A and E in o/w emulsions for cosmetic application.

The effectiveness of any cosmetic product containing a functional ingredient is determined by the skin delivery of the active molecule, which is influenced by the type of carrier and the molecule itself. Furthermore, the functional ingredient should be stable in the formulation. The purpose of this paper is to study the stability of lipoic acid in the presence of vitamins A (as palmitate) and E (as acetate) in semisolids for cosmetic use. The systems formulated were studied in regard to their aspect, pH, stability under centrifugation, and rheological behavior. The chemical analyses of lipoic acid and vitamins A and E were carried out by HPLC after studying the specificity of the method employed in each case. The quantitation of the active principles was performed by HPLC with C18 (5 microm) columns. The mobile phase was methanol for the vitamins, with spectrophotometric detection at 325 nm for vitamin A and 230 nm for vitamin E. The mobile phase for lipoic acid was methanol:water (80:20) and phosphoric acid at pH 3.0, with spectrophotometric detection at 332 nm. All systems were stable to centrifugation, and no significant modification of rheological behavior was observed in relation to the base emulsion used as control. The chemical studies performed indicated that although lipoic acid is not very stable in these formulations, the presence of vitamin A favors its chemical stability.

Metabolism of the calcium and bioavailability of the salts of most frequent use.

In this article a detailed revision of the therapeutic applications of the calcium salts of most frequent use, is made. The metabolism, the bioavailability and the clinical use of the different calcium formulations vary significantly according to the salt used. The physiologic order factors, the physicochemical, the technological and the formulation ones influence in the bioavailability and, they alter the therapeutic answer. The salts of most frequent use, carbonate, citrate, pidolate, dobesilate, gluconate, phosphate and lactate, contribute in different quantities of elementary calcium. Recent studies show significant data that can be of importance in the clinical practice. The most habitual uses in the calcium salts are: for the osteoporosis treatment and prevention; in osteopenia; in hypocalcemia states; for low contribution or had absorption; as dietary supplement, according to the recommended daily ingesta and also, in vascular illnesses, like in internal hemorrhoids, phlebopathy and in diabetic retinopathy. It is concluded that it is fundamental to contribute the appropriate quantity of calcium according to the individual requirements and, on that base, to select the appropriate formula keeping in mind the variability that takes place in the absorption in connection with the salt used.

Papel del calcio y de la vitamina D en la salud ósea (parte II) / Role of calcium and vitamin D in bone health (Part II)

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O/W microemulsions for oral drug delivery.

Quaternary microemulsion compositions for oral administration using isopropyl myristate, polysorbate 80 and ethanol 96 degrees were developed and three ratio of polysorbate to ethanol were selected. Isotropic single-phase compositions were considered as microemulsions and were registered on a Pseudo-Ternary Phase Diagram. The objective was to formulate a therapeutic dose for lorazepam and loperamide in a drop liquid form. Another aim was to obtain a liquid oral formula for nifedipine taking advantage of its insured fast absorption to be used in hypertensive crises. The physical stability of the compositions was evaluated by normal aging, centrifugal resistance time and by cycling as well. The selected formulation characterization included density, pH and conductivity measurements. The particle size distribution was determined by a light scattering method and, finally the carried drugs concentration was valued. The versatility showed by this type of systems allows both to carry drugs of different physico-chemical properties and to deal with a number of pharmacotherapeutic objectives.

Microesferas de alginato para uso dermato-farmacéutico / Alginate microspheres for dermatopharmaceutical use

Se desarrollaron métodos simples y reproducibles para la microencapsulación de ácido all-trans-retinoico (AR) y ácido salicílico (AS) en forma disuelta, con el objeto de mejorar sus aplicaciones terapéuticas y establecer criterios comparativos de las distintas metodologías empleadas. Se caracterizaron los sistemas microparticulados mediante microfotografía y distribución del tamaño de las partículas obtenidas. El desarrollo galénico de microesferas de alginato sódico, tiene como objetivo modular la liberación del AR, ya que es de interés dermatofarmacéutico optimizar la eficacia terapéutica y minimizar las reacciones secundarias, y proteger a la piel de la acción irritante del AR y del AS, preservando al AR, de la acción deletérea de agentes externos tales como el aire, la luz y la humedad (AU)

Micropartículas de alginatoconteniendo paracetamol / Alginate microparticles containing paracetamol

Micropartículas conteniendo paracetamol (PCT) han sido obtenidas por emulsificación/gelificación interna de una solución de alginato dispersada en un aceite vegetal. La morfología y la distribución de tamaño de partícula fueron determinadas. Se estudió la concentración de ión calcio resultando ser un parámetro crítico en la producción de las micropartículas. Se observó que el incremento en la concentración de calcio produce un aumento en el rendimiento total de micropartículas y en el encapsulación de PCT. La técnica desarrollada permite obtener un sistema con características micrométricas óptimas y una mayor eficacia de encapsulación de PCT (AU)

Papel del calcio y de la vitamina D en la salud ósea (parte I) / Role of calcium and vitamin D in bone health

No disponible

Consumo de antidepresivos y ansiolíticos en Argentina en 1998 / Consumption of Antidepressant and Anxiolytic drugs in Argentina in 1998

Fundamentos: Realizar una estadística sobre el consumo de drogas antidepresivas y ansiolíticas durante el año 1998 fin de obtener conclusiones que nos permitan aportar datos para racionalizar el uso. Método: Se obtuvieron los datos de distribución de las dos más grandes droguerías proveedoras de medicamentos de la Región del Nordeste Argentino y de las farmacias elaboradoras de prescripciones magistrales con éstos fármacos. Resultados: Los datos obtenidos fueron los siguientes: cantidad de unidades distribuidas por las droguerías expendedoras: 18.080 de antidepresivos y 177.205 de ansiolíticos y de las oficinas de farmacia magistrales de la zona se obtuvieron la cantidad de recetas preparadas con estas drogas: 4440. Conclusiones: Se evidencia un predominio de la medicación elaborada por la industria farmacéutica sobre los preparados magistrales realizados por las oficinas de farmacia, aunque éstos últimos son utilizados de manera más racional (AU)

Calcium alginate microspheres of Bacillus subtilis.

Microspheres of Bacillus subtilis were prepared using sodium alginate. Some typical properties of microencapsulated systems, such as microorganism content, particle size, and germination time, were studied. Calcium alginate microspheres were obtained by the emulsification method, dripping into a solution of calcium salt. The conditions of the preparation steps were very soft to produce calcium alginate microspheres containing cells with no apparent changes in general biological properties. The hydrogel matrix provides protection without preventing communication with the surrounding medium.

Microesferas de alginato con Bacillus subtilis / Alginate microspheres of Bacillus subtilis

La microencapsulación de organismos ha sido considerada como una alternativa de inmovilización de células, a fin de que éstas puedan ejercer sus funciones en forma gradual. El objetivo del presente estudio fue elaborar microesferas de Bacillus subtilis ya sea en forma esporulada como vegetativa.Microesferas de Bacillus subtilis son preparadas utilizando alginato de sodio. Algunas propiedades típicas del sistema microencapsulado, tales como contenido de microorganismos, tamaño de partícula y tiempo de germinación han sido estudiados. Las microesferas se prepararon mediante el método de coaservación-separación de fases, utilizando una etapa intermedia de emulsión múltiple. Las condiciones de preparación han sido lo suficientemente benignas para no producir cambios en las propiedades biológicas generales del sistema, pero con la protección que le otorga la matriz del hidrogel, la cual evita la directa comunicación con el medio externo.La viabilidad demostrada por las microesferas con las formas esporuladas fue significativamente superior a las de las formas vegetativas (AU)

Factors involved in the biochemical etiology of human seminal plasma hyperviscosity.

Semen rheology was studied to elucidate the biochemical basis of seminal plasma hyperviscosity. Semen proved to fit in with a power law model, by presenting a pseudoplastic behavior. Apparent viscosity at 230 s(-1) and 25 degrees C (eta(a)) was 4.3 /- 0.2 cp and 5.4 +/- 0.4 cp in normal and high-consistency semen, respectively. The effect of enzymes and mucolytic agents on human seminal plasma viscosity were evaluated by incubating normal and hyperviscous semen pool aliquots with trypsin, dithiothreitol, EDTA, alpha-amylase and deoxyribonuclease I. After incubation, trypsin treatment reduced eta(a) by 36% in normal semen and by 44% in hyperviscous semen. There was a decrease in eta(a) following incubation of hyperviscous samples with dithiothreitol (33%) and alpha-amylase (44%) that was not observed in the normal consistency samples. No decrease was observed in eta(a) after EDTA or DNAse treatment of both groups. Comparison of normal and hyperviscous seminal plasmas revealed no difference in the concentration of total proteins, DNA, or in the percentage of water content. These findings indicate that the primary substances responsible for basic normal semen rheologic behavior are proteins. A comparison of rheological properties between normal and hyperviscous semen samples indicates the existence of a highly organized network in the latter group, in which disulfide bonds and oligosaccharide chains complexed to the peptide core may play a key role.

[Production and characterization of an atenolol-reticulated povodone tablet]. / Obtención y caracterización de un complejo de atenolol con povidona reticulada.

The production of polymeric complexes in many active drugs with reticulated povidone increased dissolved component percentage. In this work made use a coevaporation technique. Complex formation has been tested by X Ray Diffractometry and Differential Scanning Calorimetry. The percentage of dissolution was determined to the USP XXIII Edition methodology. As can be seen from the results, the Atenolol-reticulated Povidone complexes has greater solubility than the Atenolol mixed with Lactose as excipient.

Semen culture, leukocytospermia, and the presence of sperm antibodies in seminal hyperviscosity.

Seminal hyperviscosity is generally thought to reveal genitourinary infection. The aim of the present work was to study this hypothesis. A total of 65 semen samples were obtained from males presenting for infertility screening. The samples were evaluated according to WHO criteria and microbiologically investigated, including culturing for Mycoplasma hominis and Ureaplasma urealyticum, and microscopic observation of Chlamydia trachomatis by a direct fluorescence assay. Determination of local antisperm antibodies was performed. Semen was categorized according to consistency: normal (n = 31) and high (n = 34). No difference was recorded either in the number of positive cultures, or in the number of species found in each sample. The number of white blood cells and the percentage of antibody-bound sperm showed no difference in the groups under study. There was no association between seminal hyperviscosity, positivity in semen cultures, number of species isolated in semen cultures, leukospermia, or presence of sperm antibodies. Further studies should be performed considering the evolution of the genital-infected patients to clarify the etiology of the hyperviscosity.

[Changes in the norms governing practices for the manufacture of pharmaceutical products: implications for the MERCOSUR]. / Evolucion de las normas oms sobre prácticas adecuadas de fabricación de productos farmacéuticos: su implicancia en el mercosur.

It is done a comparative study between the "Recommended rules for drug products manufacturing and inspection", approved in 1975 by the World Health Organization (and still in force in the MERCOSUR); and the standards published in 1992 by the WHO Expert Committee on Specifications for Pharmaceutical Preparations 32nd Report, named "Good Manufacturing Practices for pharmaceutical products". The correspondence between the regulation in force in the MERCOSUR and the Good Manufacturing Practices Inspection Guide for pharmaceutical industry, used by Health Authorities in the Common Market Member States, is analysed. It is noticed a disagreement between the rule in force and the instrument for verifying its fulfillment. The proposal of this article is the adoption by the Common Market Group, of the rules published by the WHO in 1992, and the establishment of an inspection guide which absolute agrees with it.