Determinación microanálitica de colesterol total en tejidos

En los estudios clínicos de drogas hipolipemiantes y en otros, se describe1,2 que los incrementos de colesterol total y el asociado a las LDL-C constituyen factores de riesgo principales para padecer de atereosclerosis y enfermedades asociadas a ellas, tales como infarto cardíaco, accidentes vasculares encefálicos, etc

Determination_of D003 by capillary gas chromatography

D003 is a mixture of saturated very long-chain fatty acids ranging from 24 to 36 carbon atoms, obtained from sugar cane (Saccharum officinarum L.) wax, with antiplatelet, 'antithrombotic, antioxidant and cholesterol-lowering effects . A capillary gas chromatographic method for the determination of this product was developed and validated . The acids were analyzed as methyl ester derivatives and separated in a BP-5 widebore column using 1-nonacosanoic acid as internal standard . A good linearity (r > 0 .99; CVs of the response factors and of the slopes lower than 5 and 2 %, respectively) ; as well as absence of bias was found for both, total and individual acids in the whole studied concentration range, from 30 to 150 % of the nominal mass . Quantitative recoveries (98 .9 and 100 .62 %) and good intermediate precision (CV = 0 .96 %) were also obtained . The specificity study showed no interferences regarding the determination of this mixture, once the samples were submitted to stress conditions. According to these results, it can be ensure that the validated procedure is appropriate for the quality control and stability studies of this product

Metodologías analíticas aplicadas al D003, nuevo ingrediente activo obtenido de la cera de la caña de azúcar

El D003 es un nuevo ingrediente activo, formado por una mezcla de ácidos grasos saturados lineales entre 24 a 36 átomos de carbono, el cual es aislado y purificado a partir de la cera de caña de azúcar (Saccharum officinarum L.) y ha mostrado efecto hipolipemiante, antiagregante plaquetario, anti-oxidante y antiosteopor ótico. A partir de este ingrediente activo se han elaborado suspensiones acuosas para los estudios preclínicos y tabletas con dosis de 5 y 10 mg, todo lo cual ha requerido el desarrollo y validación de metodologías analíticas por cromatograf ía de gases para su determinación en las diferentes formas en que se le utiliza. Estas metodologías se basan en el empleo de una columna semicapilar DB-5 y del ácido 1-nonadecanoico como patrón interno. Los ácidos grasos son analizados como ésteres metílicos, para cuya formación se usa una disolución de ácido clorhídrico al 5 % en metanol. Los resultados de las validaciones demostraron que estas metodolog ías son específicas, al no haber interferencias de otros componentes en las señales de los ácidos grasos, ni siquiera al someter previamente los productos a condiciones extremas de degradación. Estas metodologías también resultaron lineales (coeficientes de correlación > 0,99) y exactas (recobrados totales entre 99,6 y 100,3 %) entre el 50 y el 150 % de las masas nominales. La repetibilidad, precisión intermedia y reproducibilidad en las determinaciones presentaron coeficientes de variación < 2,1 %

Stability studies of film-coated tablets containing 5 mg of D-003 as active ingredient

D-003 is a new under research drug with potential use for preventing or treating atherothrombotic diseases. This product is made up of a mixture of very high molecular weight aliphatic acids (C24:0 to C36:0) purified from sugar cane (Saccharum officinarum, L.) wax. The aim of this study was to determine the stability of the proposed formulation of D-003 5 mg film-coated tablets, following International Harmonization Conference guidelines for knowing their possible specifications change on storage conditions and for predicting their expiration date. Specifications such as D-003 content, color, tablet weight, hardness, disintegration time, and microbial content were assessed. Stress testing included acid hydrolysis, thermolysis, oxidation and photolysis. In addition, accelerated studies under drastic conditions: 40 oC and 75 % of relative humidity (RH) as well as long-term studies (48 months) at conditions of Climatic Zones IV (30 oC and 70 % RH) and II (25 oC and 60 % RH) were also conducted using three batches. Tablets were crushed to a fine powder and the active ingredient with chloroform was extracted in a hot way. The acids were converted to methyl esters and in a BP-5 wide-bore capillary column by gas chromatography were analyzed. Quantification by the internal standard method, using 1-nonacosanoic acid was carried out and peaks purity by gas chromatography - mass spectrometry was confirmed. No significant changes or trends either on the content of D-003 or on other specifications were found in any study

Five-year stability studies by GC and GC-MS of D-003 (a mixture of C24:0 to C36:0 fatty acids) alone and in 5 mg film-coated tablets

El D-003 es nuevo producto con efectos reductores del colesterol y antioxidantes. Se trata de una mezcla de ácidos grasos alifáticos de alto peso molecular (C a C ) purificados de la cera de caña de azúcar (Saccharum officinarum, L.), donde el ácido octacosanoico es el componente mayoritario. Se determinó la estabilidad del D-003 en estado natural y en forma de tabletas recubiertas de 5 mg, siguiendo las guías de la ICH. Los estudios de validación de los métodos por CG demostraron una buena linealidad (r > 0,9994; CVs de los factores de respuesta y de las pendientes 0.9994, RSDs of the response factors and of the slopes < 5 and 2%, respectively), high accuracy (recoveries from 98.9 to 100.6%) and precision (RSD < 2% for repeatability and reproducibility). Specifications such as content, color, tablet weight, hardness, disintegration time, and microbiological content were assessed. Stress testing included acid hydrolysis, thermolysis, oxidation and photolysis. In addition, accelerated studies (12 months) under drastic conditions: 40 °C and 75% of relative humidity (RH) as well as long-term studies (60 months) at conditions of Climatic Zones IV (30 °C and 70% RH) and II (25 °C and 60% RH) were also conducted using three batches of AI and tablets. No significant changes or trends neither on the content nor on other specifications were found in any study. Overall, D-003 is very stable as such and in 5 mg film-coated tablets, with a shelf life of 5 years in climatic conditions of Zones IV and II.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Validation of an analytical methodology for the quantitative analysis of petroleum hydrocarbons in marine sediment samples

This work describes a validation of an analytical procedure for the analysis of petroleum hydrocarbons in marine sediment samples. The proposed protocol is able to measure n-alkanes and polycyclic aromatic hydrocarbons (PAH) in samples at concentrations as low as 30 ng/g, with a precision better than 15% for most of analytes. The extraction efficiency of fortified sediments varied from 65.1 to 105.6% and 59.7 to 97.8%, for n-alkanes and PAH in the ranges: C16 - C32 and fluoranthene - benzo(a)pyrene, respectively. The analytical protocol was applied to determine petroleum hydrocarbons in sediments collected from a marine coastal zone

Physico-mechanical characterization and interactions with excipients of D-003, a mixture of fatty acids isolated from sugar cane wax

El D-003 es un nuevo producto que consiste en una mezcla de ácidos grasos de elevado peso molecular (desde C24:0 hasta C36:0), donde cada uno de ellos está en una proporción reproducible. Este producto presenta efectos antiplaquetarios y como reductor del colesterol. Como parte de los estudios de formulación del D-003 fueron llevadas a cabo la caracterización físico-mecánica y su interacción con excipientes para tabletas. El presente estudio utilizó la calorimetría diferencial de barrido (CDB) y la termogravimetría (TG) con el objetivo de evaluar la estabilidad térmica y las transiciones características del D-003 en presencia de diversos excipientes. Fueron medidas otras propiedades, tales como el ángulo de contacto, solubilidad, humectabilidad, distribución del tamaño de partículas, propiedades de fluido, densidades por asentamiento, por vertido y de alta presión, así como la reducción de volumen bajo compresión. Estos estudios, según nuestro conocimiento, no han sido previamente reportados para estos ácidos. Los estudios por CDB demostraron que no hubo interacción química o física entre el D-003 y los excipientes investigados. También, los análisis termogravimétricos probaron la elevada estabilidad térmica del D-003, el cual es estable y funde sin descomposición hasta temperaturas tan elevadas como 220 °C. Los lotes industriales estudiados mostraron adecuada pureza y distribución uniforme del tamaño de partícula, buenas propiedades de fluido, compresibilidad y cohesión, lo cual sustenta que sea un polvo apropiado para la elaboración de tabletas revestidas como forma terminada. Sin embargo, la muy baja solubilidad del D-003 en la mayoría de los disolventes, especialmente en agua, es el aspecto más crítico para el desarrollo la forma terminada, lo cual es importante para decidir la formulación del revestimiento.D-003 is a new product consisting of a mixture of fatty acids of very high molecular weight (from C24:0 to C36:0) in a reproducible proportion each, with cholesterol-lowering, and antiplatelet effects. As part of the formulation studies of D-003 a physico-mechanical characterization and its interaction with tablet excipients were carried out. The present study used differential scanning calorimetry (DSC) and thermogravimetry (TG) in order to evaluate the characteristic transitions and thermal stability of D- 003 in presence of several excipients. Other properties, such as the angle of contact, solubility, wettability, particle size distribution, flow properties, tapped, bulk and at high pressure densities, as well as volume reduction under compression were measured. These studies, to our knowledge, have not been previously reported to these fatty acids. DSC studies demonstrated that there was no chemical or physical interaction between D-003 and the investigated excipients. Also, thermogravimetric analysis proved the high thermal stability of D-003, which melts without decomposition and is stable at temperatures as high as 220 °C. Industrial batches of D-003 showed adequate purity and uniform particle size distribution, good flow properties, compressibility and compactability, which support a suitable powder for manufacturing film-coated tablets as finished forms. Nevertheless, the very low solubility of D-003 in most solvents, especially in water, is the most critical aspect for developing the finished form, being relevant to decide the coating formulation.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p&lt;0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p&lt;0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status