Solubility data and solubility parameters of barnidipine in different pure solvents / Solubilidad y parámetros de solubilidad del barnidipino en diferentes disolventes puros

Introducción: Los estudios de solubilidad y la obtención de datos fisicoquímicos de fármacos en disolventes puros pertenecientes a diferentes clases químicas resultan claves para desarrollar nuevas formulaciones de medicamentos. En este trabajo se calcularon los parámetros de solubilidad parciales de Hansen (HSP) para evaluar la miscibilidad y las interacciones intermoleculares del barnidipino en diecisiete disolventes puros. Además, se compararon los valores experimentales obtenidos con los teóricos calculados según la estructura del barnidipino, para analizar la influencia de las relaciones soluto-soluto, soluto-solvente de los grupos de contribución aditivos, en las propiedades químicas y físicas del barnidipino con los solventes de diferente polaridad ensayados, para aportar información relevante para su uso en la industria farmacéutica. Método: La solubilidad en equilibrio del barnidipino en los disolventes seleccionados se determinó usando el método clásico de agitación en matraces seguida de un análisis por espectrofotometría UV a 298,15 K, y se calcularon los parámetros parciales de solubilidad con la aplicación de métodos teóricos de contribución de grupo, propuestos por Hoftyzer-Van Krevelen y Fedors. El modelo KAT-LSER se usó para investigar el efecto del solvente basado en el concepto de relaciones de energía de solvatación lineal. La fracción molar se obtuvo considerando las densidades de las soluciones. Los análisis en fase sólida se realizaron por calorimetría diferencial de barrido. Resultados: La modificación introducida en el método de Hansen, es decir, el empleo de lnX2 como variable dependiente proporcionó excelentes resultados. Los valores más altos de solubilidad se han encontrado en los disolventes polares. Se observa que las interacciones intermoleculares solvente-solvente y soluto-solvente con enlaces de hidrógeno y fuerzas de van der Waals, influyeron significativamente en la solubilidad del fármaco. (AU)

Introduction: Solubility studies and obtaining physicochemical data on drugs in pure solvents belonging to differ-ent chemical classes are key to developing new drug formulations. In this work, Hansen partial solubility parame-ters (HSP) were calculated to assess the miscibility and intermolecular interactions of barnidipine in seventeen pure solvents. The comparison of the results obtained with the theoretical values calculated according to the structure of barnidipine, were valuable to analyse the influence of the solute-solute, solute-solvent relationships of the additive contribution groups, on the chemical and physical properties of this molecule with the solvents of different polarity tested, to provide relevant information highly useful in the pharmaceutical industry. Method: Equilibrium barnidipine solubilities in mono-solvents was determined using the classical shake-flask method, followed by UV-spectrophotometric analysis at 298.15 K. The partial solubility parameters were calculated by applying theoretical group contribution methods, proposed by Hoftyzer-Van Krevelen and Fedors. The KAT-LSER model was used to investigate the effect of solvent based on the concept of linear solvation energy relationships. The mole fraction was obtained from the densities of the solutions. Solid-phase analyses were made by calorimetry differential scanning. Results: The modification introduced in the extended Hansen method, that is, the use of lnX2 as the dependent variable, provided excellent results. The highest solubility values have been found in polar solvents. It is observed that solvent-solvent and solute-solvent intermolecular interactions through hydrogen bonds and van der Waals forces, significantly influence drug solubility (AU)

Development of Chitosan/Sodium Carboxymethylcellulose Complexes to Improve the Simvastatin Release Rate: Polymer/Polymer and Drug/Polymer Interactions' Effects on Kinetic Models.

Simvastatin (SIM) is a potent lipid-lowering drug used to control hyper-cholesterolemia and prevent cardiovascular diseases. SIM presents low oral bioavailability (5%) because of its low aqueous solubility. In this work, polyelectrolyte complexes (PEC) are developed with different chitosan (CS) and carboxymethylcellulose (CMC) ratios that will allow for an increase in the SIM dissolution rate (2.54-fold) in simulated intestinal medium (pH 4.5). Scanning Electron Microscopy (SEM) images revealed highly porous structures. The changes between both complexes, PEC-SIM:CS:CMC (1:1:2) and (1:2:1), were related to the relaxation of the polymer chains upon absorption of the dissolution medium. Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (XRPD) studies were used to evaluate the polymer/polymer and drug/polymer interactions on the different PEC-SIM:CS:CMC ratios. In addition, the PEC-SIM:CS:CMC (1:2:1) complex exhibited a high ratio of protonated amino groups (NH3+) and an increase in intramolecular hydrogen bonds, which were correlated with a high expansion of the interpolymer chains and an increase in the SIM dissolution rate. Different kinetic models such as zero-order, first-order, Higuchi and Korsmeyer-Peppas were studied to evaluate the influence of CS/CMC ionic interactions on the ability to improve the release rate of poorly soluble drugs.

Study of Different Chitosan/Sodium Carboxymethyl Cellulose Proportions in the Development of Polyelectrolyte Complexes for the Sustained Release of Clarithromycin from Matrix Tablets.

This study investigated the combination of different proportions of cationic chitosan and anionic carboxymethyl cellulose (CMC) for the development of polyelectrolyte complexes to be used as a carrier in a sustained-release system. Analysis via scanning electron microscopy (SEM) Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) confirmed ionic interactions occur between the chitosan and carboxymethyl cellulose chains, which increases drug entrapment. The results of the dissolution study in acetate buffer (pH 4.2) showed significant increases in the kinetic profiles of clarithromycin for low proportions of chitosan/carboxymethyl cellulose tablets, while the tablets containing only chitosan had high relaxation of chitosan chains and disintegrated rapidly. The Korsmeyer-Peppas kinetic model for the different interpolymer complexes demonstrated that the clarithromycin transport mechanism was controlled by Fickian diffusion. These results suggest that the matrix tablets with different proportions of chitosan/carboxymethyl cellulose enhanced the ionic interaction and enabled the prolonged release of clarithromycin.

Estudio descriptivo de los subsectores productores y comercializadores de medicamentos y fitoterapéuticos en Bogotá / Descriptive study for the subsectors which manufacture and sell pharmaceutics and phytotherapeutics in Bogotá

Por iniciativa académica y aplicando una metodología de investigación no experimental transeccional descriptiva, se buscó estudiar mediante un censo los subsectores de medicamentos y productos a base de recursos naturales, también denominados fitoterapéuticos, de la ciudad de Bogotá, Colombia. La Universidad ha dado un primer paso, caracterizando la industria farmacéutica en términos de su composición, localización, origen, actividad económica, agremiación, ocupación del profesional químico farmacéutico, formas farmacéuticas que se comercializan y canales de distribución, entre las más importantes. Se encontró que en la ciudad de Bogotá se concentra el 60% de los establecimientos productores de medicamentos del país y el 78% de productores de fitoterapéuticos; por tanto, conocer de las características de los subsectores de medicamentos y fitoterapéuticos permitirá un acercamiento de la Academia, consecuente con las necesidades identificadas en el sector, y establecer las prioridades de éste en términos de los procesos de transformación de materiales para identificar futuras investigaciones.

Since academic initiative and applying a non experimental transectional descriptive methodology of investigation, we looked for studying by means of a census, the subsectors pharmaceutics and products based on natural resources sector, also named phytotherapeutics, located in Bogotá city, Colombia. The University has given the first step, characterizing the pharmaceutical industry in terms of its composition, location, nationality, economic activity, guild, conquest by the pharmaceutical chemist professional, pharmaceutical dosage forms that are commercialized by them and track of distribution, among the most significant. It was found that in Bogotá city there are 60% of the manufacturer institutions of pharmaceutics in the country and about 78% of the manufacturer institutions of phytotherapeutics, therefore the knowledge of the characteristics for the subsectors on pharmaceutics and phytotherapeutics will allow an approach of the academy, consistent with the identified needs for the sector, substantiating the priorities of this in terms of the processes of transformation of materials in order to identity next researches.