Study of tocopherol content and its potential antioxidant activity in commercial lipid emulsions for parenteral nutrition.

The objective of this study was to determine the content and evaluate the potential antioxidant effect of tocopherols in commercially available lipid emulsions, using a simple validated method adequate for further routine use. During the study, variability between manufacturers as well as between three non-consecutive batches of the same emulsion was observed. Furthermore, addition of α-tocopherol to lipid emulsions as excipient yields more stable emulsions and potentially a beneficial clinical effect. It was concluded that the variation of the tocopherol content between batches implies the importance of control and specification of tocopherol content by the manufacturers.

Improving tablet coating robustness by selecting critical process parameters from retrospective data.

CONTEXT: Although tablet coating processes are widely used in the pharmaceutical industry, they often lack adequate robustness. Up-scaling can be challenging as minor changes in parameters can lead to varying quality results. OBJECTIVE: To select critical process parameters (CPP) using retrospective data of a commercial product and to establish a design of experiments (DoE) that would improve the robustness of the coating process. MATERIALS AND METHODS: A retrospective analysis of data from 36 commercial batches. Batches were selected based on the quality results generated during batch release, some of which revealed quality deviations concerning the appearance of the coated tablets. The product is already marketed and belongs to the portfolio of a multinational pharmaceutical company. RESULTS: The Statgraphics 5.1 software was used for data processing to determine critical process parameters in order to propose new working ranges. DISCUSSION AND CONCLUSIONS: This study confirms that it is possible to determine the critical process parameters and create design spaces based on retrospective data of commercial batches. This type of analysis is thus converted into a tool to optimize the robustness of existing processes. Our results show that a design space can be established with minimum investment in experiments, since current commercial batch data are processed statistically.

p53 gene discriminates two ecologically divergent sister species of pine voles.

Genes with relevant roles in the differentiation of closely-related species are likely to have diverged simultaneously with the species and more accurately reproduce the species tree. The Lusitanian (Microtus lusitanicus) and Mediterranean (M. duodecimcostatus) pine voles are two recently separated sister species with fossorial lifestyles whose different ecological, physiological and morphological phenotypes reflect the better adaptation of M. duodecimcostatus to the underground habitat. Here we asked whether the differentiation of M. lusitanicus and M. duodecimcostatus involved genetic variations within the tumour suppressor p53 gene, given its role in stress-associated responses. We performed a population-genetic analysis through sequencing of exons and introns of p53 in individuals from sympatric and allopatric populations of both the species in the Iberian Peninsula in which a unidirectional introgression of mitochondrial DNA was previously observed. We were able to discriminate the two species to a large extent. We show that M. duodecimcostatus is composed of one genetically unstructured group of populations sharing a P53 protein that carries a mutation in the DNA-binding region not observed in M. lusitanicus, raising the possibility that this mutation may have been central in the evolutionary history of M. duodecimcostatus. Our results provide suggestive evidence for the involvement of a master transcription factor in the separation of M. lusitanicus and M. duodecimcostatus during Microtus radiation in the Quaternary presumably via a differential adaptive role of the novel p53 in M. duodecimcostatus.

Relationships between surface free energy, surface texture parameters and controlled drug release in hydrophilic matrices.

The study of controlled release and drug release devices has been dominated by considerations of the bulk or average properties of material or devices. Yet the outermost surface atoms play a central role in their performance. The objective of this article has been to characterize the surface of hydrophilic matrix tablets using the contact angle (CA) method to ascertain the surface free energy, and atomic force microscopy (AFM) and confocal microscopy (CM) for the physical characterization of the surface of the hydrophilic matrix. The surface free energy results obtained show that hydroxypropylmethylcellulose K15M hinders the spreading of water on the surface of the tablet, such that the concentration of HPMC K15M increases the reaction rate of the hydrophobic interactions between the chains of HPMC K15M which increases with respect to the rate of penetration of water into the tablet. In this study, we developed a new method to characterize the swelling of the tablets and established a relationship between the new method based on microswelling and the swelling ratio parameter. The surface texture parameters have been determined and the morphology of the tablets of the different formulations and the evolution of the surface morphology after interacting with the water, swelling and forming a gel layer were characterized. This work represents significant progress in the characterization of matrix tablets.

Quality by Design approach to understand the physicochemical phenomena involved in controlled release of captopril SR matrix tablets.

The aim of this study is to obtain swelling controlled release matrix tablets of captopril using the Quality by Design methodology (ICH Q8) and to know the transport mechanisms involved in captopril release. To obtain the area of knowledge, the design of experiments studying the effect of two components (HPMC K15M and ethylcellulose) at different levels has been applied, with the captopril dissolution profile as the product's most important critical quality attribute (CQA). Different dissolution profiles have been obtained with the design of experiments performed, which is a key factor in the development of controlled release matrix tablets. Kinetic analysis according to the equations of Higuchi and Korsmeyer-Peppas demonstrates that the release mechanism is a mechanism of erosion when the whole percentage of the polymer is ethylcellulose, and a diffusion mechanism when the whole percentage of the polymer is HPMC K15M. The physico-chemical characteristics of the gel layer determine the release rate of captopril. The thickness of the gel layer, the porosity which is formed in the matrix upon contact with water, pore size, the swelling rate, the erosion rate of the matrix, and the physico-chemical characteristics of captopril, are factors related to the kinetic equations described and that allow us to predict the release mechanism of captopril. A new relationship of the kinetic equations governing the in vitro behavior with the physical characteristics of the gel layer of the different formulations has been established. This study shows that the size of water-filled pores and the degree of crosslinking between the chains of HPMC K15M of the matrix are related to the exponent n of the Korsmeyer-Peppas equation and the type of transport of the captopril from within the matrix to the dissolution medium, that is, if the transport is only through water-filled pores, or if a combination of diffusion occurs through water-filled pores with a transport through continuous polymeric networks.

The use of the SeDeM diagram expert system for the formulation of Captopril SR matrix tablets by direct compression.

The SeDeM diagram expert system has been used to study excipients, Captopril and designed formulations for their galenic characterization and to ascertain the critical points of the formula affecting product quality to obtain suitable formulations of Captopril direct compression SR matrix tablets. The application of the SeDeM diagram expert system enables selecting excipients with in order to optimize the formula in the preformulation and formulation studies. The methodology is based on the implementation of ICH Q8, establishing the design space of the formula with the use of experiment design, using the parameters of the SeDeM diagram expert system as system responses.

Characterization of alginate beads loaded with ibuprofen lysine salt and optimization of the preparation method.

The parameters influencing alginate ionotropic gelation and the production of alginate beads loaded with hydrosoluble ibuprofen lysine salt (IBU-L) were studied, as well as the optimization of the method for its attainment. A three-factor and three-level factorial design (3(3)) was carried out to determine the influence of three experimental variables: polymer concentration, CaCl2 concentration, and curing time on the dependent variables drug load and encapsulation efficiency. The effect of the pH used in the preparation bath was also evaluated. Concentrations of CaCl2 and pH of gelling bath were seen to affect bead formation and stability as well as their ability to properly entrap the drug. In this work, IBU-L was used as a model of a non-steroidal anti-inflammatory drug with good solubility in alginate solutions. IBU-L was successfully encapsulated in alginate beads obtained by the ionotropic gelation method. The obtained alginate matrixes are able to modify the release of the entrapped IBU-L and this occurs in a pH-sensitive way that can be correlated with the swelling behaviour of the alginate-produced beads. Morphological characteristics were evaluated by means of scanning electron microscopy.

Studies on the codling moth (Lepidoptera: Tortricidae) response to different codlemone release rates.

The response of the codling moth (Cydia pomonella L. (Lepidoptera: Tortricidae)) to different emission values of its main pheromone component, 8E,10E-dodecadien-1-ol (codlemone), was investigated in three field trials conducted in plots without mating disruption treatments. Moth catches obtained in traps baited with pheromone dispensers were correlated with the corresponding codlemone release rates by multiple regression analysis. In a preliminary trial conducted in Lleida (NE Spain), a decreasing trend of captures was observed based on increasing pheromone levels. After this, the pheromone release profiles of the pheromone dispensers were studied, in parallel with the field trials, by residual codlemone extraction and gas chromatography quantification. In the trials carried out in Asturias (NW Spain), a correlation between trap catches and emission levels (within the range from 11 to 1,078 µg/d) was found and fitted a logarithmic model. Captures followed a decreasing linear trend in the range of emission rates from 11 to 134 µg/d. Given that release values comprised between 11 and 67 µg/d did not lead to significantly different catches in traps, this emission range could be considered to develop effective formulations for attraction purposes when mating disruption is not acting in the environment.

Impact of physical parameters on particle size and reaction yield when using the ionic gelation method to obtain cationic polymeric chitosan-tripolyphosphate nanoparticles.

Ionic gelation is the most frequently used method to obtain chitosan-tripolyphosphate nanoparticles due to its simplicity and because it does not generate waste solvents in the samples prepared. This paper presents a study of the physical factors involved in this method for obtaining nanoparticles in order to determine which of them significantly influences the particle size of polymeric nanoparticles made from low-molecular-weight chitosan, without any additional chemical treatment, with the aim of standardising and optimising the method conditions, in addition to establishing the reaction yield. The results indicate that stirring speed during ionic gelation reaction is decisive for the size of the nanoparticles obtained. Furthermore, it thus follows that the stirring speed during ionic gelation significantly affects reaction yield, and therefore, by manipulating this parameter a greater proportion of nanoparticles of a given size range can be obtained.

La formación de los residentes de Pediatría a debate: resultados de la encuesta realizada a pediatras colaboradores docentes en la Comunidad de Madrid / Debate on the training of pediatric residents: results of the survey on pediatricians, teaching collaborators in the Community of Madrid

Introducción: la junta directiva de la Asociación Madrileña de Pediatría de Atención Primaria (AMPap) decidió realizar una encuesta a los socios colaboradores en la docencia de residentes de Pediatría cuatro años y medio después de que fuera publicada la resolución conjunta de los Ministerios de Sanidad y Consumo y de Educación y Ciencia, por la que se establecían los requisitos generales para la acreditación de centros de salud vinculados a unidades docentes acreditadas para la formación de especialistas en Pediatría y sus áreas específicas. Material y métodos: en junio de 2011 enviamos a la lista de correo de nuestra sociedad una encuesta diseñada con la herramienta Google Docs® y dirigida a los socios que fueran asiduos colaboradores en la docencia de residentes de Pediatría. Contestaron a 12 preguntas relacionadas con la ubicación de su centro de trabajo, hospital de referencia, número de residentes que reciben, tiempo de rotación y distribución. Resultados: hemos obtenido 47 respuestas y hemos comprobado que menos de la mitad de los residentes de Pediatría hacen la rotación obligatoria en Atención Primaria (AP). Conclusiones: hemos comprobado cómo, a pesar de que más de la mitad de los pediatras madrileños desarrollan su labor en la AP y de que la Comisión Nacional de la Especialidad ha dado importancia a este hecho planteando una rotación obligatoria de tres meses, solo dos de cada cinco residentes de Pediatría en nuestra comunidad la cumplen. Planteamos la necesidad de que algún pediatra colaborador en la docencia o los coordinadores de pediatras de las Direcciones Asistenciales formen parte de las Comisiones de Docencia de los hospitales o de las nuevas Unidades Multiprofesionales y que la labor docente de los pediatras colaboradores sea valorada curricular y profesionalmente(AU)

Introduction: the board of directors of the Madrid Primary Care Paediatrics’ Association (AMPap) decided to conduct a survey to partner teachers of pediatric residents four and a half years after the joint resolution of the Ministries of Health and Consumer Affairs and Education and Science was published. In this resolution, the general requirements for accreditation of health centers linked to accredited training units for specialists in pediatrics were stablished. Material and methods: in June 2011 a survey designed with Google docs was sent to the mailing list of our society, and directed to partners who were regulars in the teaching of pediatric residents. They answered 12 questions related to their workplace location, reference hospital, number of residents received, distribution, and turnover time. Results: we obtained 47 answers and found that less than half of the pediatric residents do the mandatory rotation in primary care. Conclusions: we have seen that, despite the fact that more than half of Madrid’s pediatricians develop their work in primary care and that the Specialty National Commission gives importance to this fact, hence considering a mandatory rotation of three months, only two out of five pediatric residents in our community met this requirement. We arise the need that a pediatrician teaching collaborator or the Pediatricians Coordinators in care Management take part in the new Multiprofessional Units and that the pediatric teaching collaboration be valued in the curriculum and the profession(AU)

La Pediatría en Atención Primaria en Madrid / Primary Care Pediatrics in Madrid

La Pediatría en Atención Primaria en Madrid ha pasado una época complicada. La situación de escasez y aislamiento de los pediatras en los equipos de Atención Primaria nos hace vulnerables para los gestores. La creación en los hospitales de los nuevos contratos mixtos de Facultativo Especialista de Área de Pediatría para cubrir las guardias y las plazas vacantes en los centros de salud ha supuesto una amenaza para la permanencia de los pediatras en el primer nivel asistencial. La contratación de pediatras en Atención Primaria ha permanecido bloqueada por la Administración Sanitaria madrileña durante diez meses para favorecer el desarrollo de estos nuevos contratos. Con la ayuda de sociedades profesionales pediátricas y de ciudadanos, la junta directiva de la Asociación Madrileña de Pediatría de Atención Primaria (AMPap) ha recopilado más de 24 000 firmas para el Manifiesto en defensa del pediatra de cabecera”, y tras el debate en la Asamblea de Madrid hemos conseguido desbloquear la contratación de pediatras para los centros de salud (AU)

Primary Care Pediatrics in Madrid has had a complicated time lately. The current situation of isolation and scarcity of pediatricians in primary care teams makes us all vulnerable to managers. The creation of the new “mixed” contracts to cover the current necessities of guards in hospitals as well as vacancies in primary care centers have supposed a threat to the presence of pediatricians at the first level of child care. The hiring of pediatricians in primary care has been blocked by the Madrid’s political administration for 10 months to encourage the growth of these new contracts. The board of the Primary Care Pediatrics Association of Madrid (AMPap) with the help of other pediatrics professional societies and citizens, has collected over 24 000 signatures for the Manifesto in defense of the general pediatrician and after the parliamentary debate in the Assembly of Madrid we have achieved to unblock the hiring of pediatricians for the health centers (AU)

Total organic carbon (VCSN and VWP) and HPLC analysis for cleaning validation in a pharmaceutical pilot plant.

This paper presents a useful method using total organic carbon analyzers employing both combustion and wet oxidation for validating equipment cleaning procedures and verifying cleaning in a pharmaceutical pilot plant. The results are compared with those obtained using high-performance liquid chromatography. The study summarizes the initial steps that should be taken into account and focuses particularly on the solutions to some of the most critical considerations (e.g., glass material, detection and quantification limits, recovery). Also described are the calculation of control limits and the good results obtained.

Actualización en Medicina de Familia: Drogas de uso y abuso. Mitos, realidades y aspectos prácticos en la consulta de Atención Primaria / Up-date in Family Medicine: Use and abuse of drugs. Myths, realities and practical aspects in the primary care consultation

El término pharmacon significa remedio y veneno. Que apliquemos un sentido u otro al término depende del grado de pureza, de la dosis y las modalidades de empleo, de las condiciones de acceso y las pautas culturales de consumo, junto al estado físico, emocional, mental y espiritual de quien lo consume. Cada cultura tiene sus drogas permitidas y sus drogas prohibidas, controladas o para el uso de unos pocos. Los términos ilegal, prohibido y de consumo restringido no son exclusivos de nuestra época. En la actualidad, lo que sí se evidencia es una edad de inicio más temprana y cambios en los patrones de consumo, básicamente por la mayor variedad de sustancias en nuestro entorno y más accesibilidad. El tabaco y el alcohol siguen siendo las que más problemas de salud generan en nuestro medio, el cannabis es la droga ilegal más prevalente y la cocaína la que más demandas de atención médica requiere. Este artículo no abordará las drogas legales, no es tampoco un estudio exhaustivo de las ilegales, ni pretende entrar en definiciones o tratamientos. Se trata de abordar el tema desde un punto de vista racional, poniendo al alcance del médico una perspectiva práctica del porqué se llega al consumo, qué términos se usan en la calle y por qué están en auge estas sustancias entre los jóvenes (AU)

The term pharmacon means remedy and poison. Whether it is considered a remedy or poison depends on the level of purity, the dose and how it is used, accessibility conditions and how its consumption is accepted culturally along with the consumer's physical, mental, emotional and spiritual condition. Every culture has its own permitted and prohibited drugs, that are controlled or only for the use of a few. The terms illegal, prohibited and restricted use are not new to this era. What is currently being seen is that there are some changes taking place in the consumption patterns, basically because of the wide variety of substances available all around us, easier access and younger age of initiation. Tobacco and alcohol continue to be the principal cause of health problems in our environment. Cannabis is the most prevalent illegal drug and cocaine is the drug that generates the most need for medical attention. This article does not discuss illegal drugs, nor is it a comprehensive study of illegal drugs. We will not go into definitions and treatments, it is our attempt to broach the subject from a rational standpoint allowing doctors to have a practical perspective as to how we have reached this point, what are the current street terms and why it is currently so popular amongst our youth (AU)

In vitro evaluation of the effectiveness and cytotoxicity of meglumine antimoniate microspheres produced by spray drying against Leishmania infantum.

The aim of the present study was to evaluate the in vitro activity and cytotoxicity of meglumine antimoniate microspheres produced by spray drying on Leishmania infantum and the effect of the excipients used in them. The parasite strain shows sensitivity to the meglumine antimoniate microspheres prepared. All the antimony IC50 values from encapsulated meglumine antimoniate (3.80 +/- 0.34 to 9.53 +/- 0.70 microg SbV/ml for promastigotes assay) are considerably lower compared to the mean value of IC50 in Glucantime solution (112 +/- 12.74 microg SbV/ml). Interesting IC50 values for the excipient chitosan (112.64 +/- 0.53 mg/ml for promastigotes and 100.81 +/- 26.45 mg/ml for amastigotes) were obtained (without cytotoxic activity), whereas the rest of the excipients did not show any activity. This new delivery system could offer a new pharmacological tool for the treatment of leishmaniosis that reduces the doses required, lowering toxic side effects because of meglumine antimoniate.

Method for the development of topical medicinal aerosols using liquified hydrocarbon gas.

Low chain liquid hydrocarbons (LH) at room temperature and atmospheric pressure can be used to simulate the effect of gas hydrocarbons (GH) in aerosol systems without the need of using pressured flasks. Samples of different tetracycline formulations were tested with LH and GH in order to study their behaviour and physicochemical stability in the system. The results showed a similar behaviour between samples when LH or GH were used, suggesting the use of LH to simulate the effect of GH introduction in the system, as a useful predictive method for the development of pressured aerosol formulations without using pressured containers in early steps of the process, such as pre-formulation studies.

Aplicación del diseño experimental a la optimización farmacéutica de procesos de fabricación de medicamentos / Application of the experimental design to the pharmaceutical optimization on the production process of drugs

A partir de una fórmula famacotécnicamente correcta y tras concluir las pruebas de cualificación individuales de los equipos se plantea el último paso del desarrollo galénico, entendiéndose como tal la optimización del proceso de elaboración. Para la optimización se aplica la técnica del diseño de experimentos a fin de determinar la combinación óptima y conjunta de los parámetros críticos del proceso de elaboración que dan un valor de respuesta óptima. Las respuestas del proceso de compresnión a optimizar (fórmula para realizar en las prácticas de pregrado de la licenciatura de farmacia) pueden ser varias, en este caso se escogieron la riqueza media de los comprimidos (de una muestra de 10 comprimidos), el % de disolución a los 30 minutos (de una muestra de 6 comprimidos) y la dureza (de una muestra de 10 comprimidos), cuyos resultados se presentan resumidos, los cuales demuestran la validez y utildad de esta herramienta para la validación farmacéutica rutinaria, herramienta que será muy útil para el desarrollo pleno de las normativas ICH Q8, ICH q9 y ICH Q10, dentro del desarrollo galénico y la validación

From a formula tecnologically correct and after concluding the individual tests of qualification of the equipments the last step of the phamaceutical development starts, understanding itself as that of the optimization of teh process of production. For the optimization the technology of the experimental design is applied in order to determine the ideal combination of the critical parameters of the process of compression to optimizing can be different, in this case was chosen the average content of the tablets (of a sample of 10 tablets), the % of dissolution to 30 minutes (of a sample of 10 tablets). Results demonstrate the validity and usefulness of this tool for the pharmaceutical routine validation, tool that also will be very useful for the full, development of the next regulations ICH Q8, ICH Q9 and ICH Q10

Resistance of apple cultivars to Dysaphis plantaginea (Hemiptera: Aphididae): role of tree phenology in infestation avoidance.

To test the importance of flowering phenology in damage caused to apple cultivars by rosy apple aphid, Dysaphis plantaginea (Passerini) (Hemiptera: Aphididae), susceptibility of 16 cultivars was compared in greenhouse conditions after infestation with aptera and in the field after natural tree colonization. Flowering phenology was recorded in the field for all the cultivars. In both greenhouse and field trials, there were differences among cultivars with respect to aphid infestation and damage. However, damage in the greenhouse and field was not significantly correlated. Flowering phenology was also different among cultivars. Flowering order among cultivars was significantly negatively correlated with aphid infestation and damage in field, i.e., early leafing cultivars showed higher infestation and damage than late-leafing cultivars. If egg hatching occurs before bud bursting, neonate larvae will suffer a high mortality because they cannot feed on these late cultivars. A later recolonization of these trees is hampered because (1) winged aphids cannot live on apple but only on the secondary host, (2) apterous forms have a limited dispersal capability, and (3) aphid predators progressively increase in the orchard. Therefore, synchronization between egg hatching and bud bursting is of critical importance in the success or failure of infestation.

Stability evaluation of amoxicillin in a solid premix veterinary formulation by monitoring the degradation products through a new HPLC analytical method.

A methodology (by VICH guidelines) for the stability evaluation of amoxicillin in granular premixes is described. This method is based on the monitoring of the degradation products formed during the stability study by a new HPLC-RP method, which has been developed and validated for the simultaneous determination of amoxicillin and its degradation products. The method uses a Nucleosil 120 C18 column and gradient elution. The mobile phase consisted of a mixture of methanol and buffer solution pH 3+/-0.05 at different proportion according to a time-schedule programme, pumped at a flow rate of 1.750 ml min(-1). The DAD detector was set at 230 nm. The validation study was carried out fulfilling the VICH guidelines in order to prove that the new analytical method, meets the reliability characteristics, and these characteristics showed the capacity of analytical method to keep, throughout the time, the fundamental criteria for validation: selectivity, linearity, precision, accuracy, sensitivity (LOD, LOQ) and robustness. The method was applied during the stability study of an amoxicillin premix in order to quantify the drug (amoxicillin) and all its degradation products to evaluate the shelf life of the new veterinary dosage form. The method also proved to be suitable as a rapid and reliable quality control method.

Estudio farmacotécnico comparativo de cinco especialidades farmacéuticas de comprimidos de paracetamol 650 mg / comparative pharmacotechnical study of five aminophen 650 mg comercial tablets

Se efectúa el estudio farmacotécnico comparativo de cinco especialidades farmacéuticas de comprimidos de paracetamol con un contenido declarado de principio activo de 650 mg, en base a los siguientes ensayos: humedad, características organolépticas, geométricas (dimensiones), de resistencia mecánica (resistencia a la rotura y friabilidad), posológicas (uniformidad de masa, riqueza y sustancias relacionadas) y de disponibilidad (disgregación y disolución)

A comparative physical test study on five commercial acetaminophen tablets 650 mg from Spanish market is carried out. The tests applied are: moisture, appearance characteristics, dimensions (diameter, thickness), hardness, weight variation, friability, disintegration, dissolution, identification, assay and related compounds

Contribución a la aplicación en la industria farmacéutica del ensayo de disolución para formas farmacéuticas sólidas / No disponible

Se efectúa una revisión del ensayo de disoluciónde formas farmacéuticas sólidas y suaplicación como control de calidad en la industriafarmacéutica. Se revisan los aspectos técnicosdel ensayo de disolución: condiciones enque debe llevarse a cabo (condiciones “sink”),equipos utilizados, aspectos analíticos y fundamentoteórico. Finalmente, se comentan losfactores que influyen en la velocidad de disolucióndel fármaco cuando se efectúa el ensayode disolución de la forma farmacéutica

The present work performs a revision of thedissolution test for solid pharmaceutical formsand its application like quality control in thepharmaceutical industry. The technical aspectsof the dissolution test are reviewed: conditionsin which it must be carried out (“sink” conditions),used equipment, analytical aspects andtheoretical foundation. Finally, the factors commentthat influence in the speed of dissolutionof the drug when the dissolution test of thepharmaceutical form takes place