Utilización de lipasas en la producción de un nuevo tipo de biodiesel que evita la generación de glicerol

Los altos precios de los combustibles derivados del petróleo están ocasionando una intensificación de la investigación de los métodos de producción de los biocombustibles, con la idea de optimizar la producción de combustibles de origen no fósil para reducir la dependencia del petróleo. En los actuales procesos de producción de biodiesel, con independencia de la escala o el tipo de proceso utilizado (continuo o discontinuo), se emplean de forma casi generalizada catalizadores en fase homogénea, como KOH. Son procesos que, además de presentar los inconvenientes intrínsecos de la catálisis homogénea, generan glicerina de baja calidad, que ha de ser tratada como residuo al caer su precio cada vez más por los excedentes que se producen. Una de las posibles soluciones a este problema y objetivo principal de esta tesis doctoral, es la producción de un nuevo tipo de biodiesel que integre la glicerina en forma de mono y diglicéridos. De esta forma se evitaría el problema de la obtención de glicerina y se incrementaría asimismo el rendimiento atómico del proceso, ya que toda la materia prima reaccionante se transformaría en biodiesel. La utilización de lipasas 1,3-regioespecíficas en condiciones óptimas, permite llevar a cabo la reacción de transesterificación de un mol de triglicérido (TG) con etanol para obtener dos moles de éster etílico y un mol de monoglicérido (MG), evitándose así la obtención de glicerina. En la actualidad, la glicerina se considera prácticamente como un residuo o un producto muy poco rentable, que además puede ocasionar graves problemas en los motores si no ha sido eliminada totalmente de la mezcla empleada como biocombustible. La aplicación de éste método enzimático simplificaría enormemente el proceso de producción, ahorrando el gran consumo de agua necesario para eliminar la glicerina, tal como se produce con la utilización del método estándar. La viabilidad de utilización de este método, así como su simplicidad, queda demostrada en esta memoria, así como en las publicaciones científicas derivadas de ella, y en más de una decena de comunicaciones a congresos

New Metformin–Citric Acid Pharmaceutical Molecular Salt: Improving Metformin Physicochemical Properties

Crystal engineering and, more specifically, the development of multicomponent materials has become an effective technique to rationally modify important physicochemical properties of solids, such as solubility and thermal stability. In this work, in order to overcome some of the problems that metformin has as a pharmaceutical, a new metformin base salt with citric acid (MTF–CIT) has been developed, which improves the thermal stability and solubility (two-fold) compared to metformin base (MTF). A complete characterization of the new crystalline form through PXRD, DSC, SCXRD, and FT–IR was conducted to ensure the purity of the new phase and provide a comprehensive view of its physicochemical behavior, thus correlating the improvement in stability and solubility with the crystal structure. The MTF–CIT salt crystallizes in the monoclinic P21/c1 spacegroup with z0 = 1. Intermolecular interactions found in MTF–CIT structure and simulated crystal morphology suggest a steric protection effect on the metformin ion that leads to the enhancement of stability in several orders of magnitude compared with MTF, as well as an improvement in solubility due to the exposition of polar groups in the biggest facets, making this new multicomponent salt a promising pharmaceutical solid.MCIU/AEI/FEDER, UE PGC2018-102047-B-I00FEDER-Universidad de Granada, Spain B-FQM-478-UGR2

Rational Coformer Selection in the Development of 6-Propyl-2-thiouracil Pharmaceutical Cocrystals

The following supporting information can be downloaded at: https://www. mdpi.com/article/10.3390/ph16030370/s1This research was funded by Project B-FQM-478-UGR20 (FEDER-Universidad de Granada, Spain). A.F. thanks MICIU/AEI of Spain (project PID2020-115637GB-I00, FEDER) for financial support.Pharmaceutical multicomponent solids have proved to efficiently modulate the physico- chemical properties of active pharmaceutical ingredients. In this context, polyphenols are interesting coformers for designing pharmaceutical cocrystals due to their wide safety profile and interesting antioxidant properties. The novel 6-propyl-2-thiouracil multicomponent solids have been obtained by mechanochemical synthesis and fully characterized by powder and single-crystal X-ray diffraction methods. The analysis of supramolecular synthons has been further performed with computational methods, with both results revealing a robust supramolecular organization influenced by the different positions of the hydroxyl groups within the polyphenolic coformers. All novel 6-propyl-2-thiouracil cocrystals show an enhanced solubility profile, but unfortunately, their thermodynamic stability in aqueous media is limited to 24 h.FEDER-Universidad de Granada, Spain B-FQM-478-UGR20Spanish Government PID2020-115637GB-I0

Production of a biodiesel-like biofuel without glycerol generation, by using Novozym 435, an immobilized Candida antarctica lipase

Background: Novozym 435, a commercial lipase from Candida antarctica, recombinant, expressed in Aspergillus niger, immobilized on macroporous acrylic resin, has been already described in the obtention of biodiesel. It is here evaluated in the production of a new biofuel that integrates the glycerol as monoglyceride (MG) together with two fatty acid ethyl esters (FAEE) molecules by the application of 1,3-selective lipases in the ethanolysis reaction of sunflower oil. Results: Response surface methodology (RSM) is employed to estimate the effects of main reaction. Optimum conditions for the viscosity, selectivity, and conversion were determined using a multifactorial design of experiments with three factors run by the software Stat Graphics version XV.I. The selected experimental parameters were reaction temperature, oil/ethanol ratio and alkaline environment. On the basis of RSM analysis, the optimum conditions for synthesis were 1/6 oil/EtOH molar ratio, 30°C, and 12.5 μl of NaOH 10 N aqueous solutions, higher stirring than 300 rpm, for 2 h and 0.5 g of biocatalyst. Conclusions: These obtained results have proven a very good efficiency of the biocatalyst in the studied selective process. Furthermore, it was allowed sixteen times the successive reuse of the biocatalyst with good performanc

Interconvertible Hydrochlorothiazide–Caffeine Multicomponent Pharmaceutical Materials: A Solvent Issue

The design of new multicomponent pharmaceutical materials that involve different active pharmaceutical ingredients (APIs), e.g., drug-drug cocrystals, is a novel and interesting approach to address new therapeutic challenges. In this work, the hydrochlorothiazide-caffeine (HCT–CAF) codrug and its methanol solvate have been synthesized by mechanochemical methods and thoroughly characterized in the solid state by powder and single crystal X-ray diffraction, respectively, as well as differential scanning calorimetry, thermogravimetric analyses and infrared spectroscopy. In addition, solubility and stability studies have also been performed looking for improved physicochemical properties of the codrug. Interestingly, the two reported structures show great similarity, which allows conversion between them. The desolvated HCT–CAF cocrystal shows great stability at 24 h and an enhancement of solubility with respect to the reference HCT API. Furthermore, the contribution of intermolecular forces on the improved physicochemical properties was evaluated by computational methods showing strong and diverse H-bond and π–π stacking interactions.Spanish Agencia Estatal de Investigacion of the Ministerio de Ciencia, Innovacion y Universidades (MICIU)European Union (EU) PGC2018-102047-B-I00MICIU/AEI from SPAIN CTQ2017-85821-

A Biofuel Similar to Biodiesel Obtained by Using a Lipase from Rhizopus oryzae, Optimized by Response Surface Methodology

A new biodiesel-like biofuel is obtained by the enzymatic ethanolysis reaction of sunflower oil with ethanol, in free solvent media, by using BIOLIPASE-R, a multipurpose alimentary additive from Biocon®-Spain that is a low cost lipase from a strain of Rhizopus oryzae. This biofuel is composed by two parts of fatty acid ethyl esters (FAEE) and one of monoglyceride (MG), which in this form integrates glycerol, through the application of the 1,3-selective lipases. Thus, this process minimizes waste generation and maximizes the efficiency of the process because no residual glycerol is produced. Response surface methodology (RSM) is employed to evaluate the main reaction parameters (reaction temperature, oil/ethanol ratio and pH) on the sunflower oil conversion. Water content and amount of lipase were also previously investigated. Regarding the results, we found that it operates optimally with a water content of the reaction medium of 0.15%, 0.05%–0.1% lipase by weight relative to the weight of oil used, 20 °C, volume ratio (mL/mL) oil/ethanol 12/3.5 and pH 12 (by addition of 50 μL of 10 N NaOH solution). These results have proven a very good efficiency of the biocatalyst in the studied selective process