Developing an accurate empirical correlation for predicting anti-cancer drugs’ dissolution in supercritical carbon dioxide

This study introduces a universal correlation based on the modified version of the Arrhenius equation to estimate the solubility of anti-cancer drugs in supercritical carbon dioxide (CO2). A combination of an Arrhenius-shape term and a departure function was proposed to estimate the solubility of anti-cancer drugs in supercritical CO2. This modified Arrhenius correlation predicts the solubility of anti-cancer drugs in supercritical CO2 from pressure, temperature, and carbon dioxide density. The pre-exponential of the Arrhenius linearly relates to the temperature and carbon dioxide density, and its exponential term is an inverse function of pressure. Moreover, the departure function linearly correlates with the natural logarithm of the ratio of carbon dioxide density to the temperature. The reliability of the proposed correlation is validated using all literature data for solubility of anti-cancer drugs in supercritical CO2. Furthermore, the predictive performance of the modified Arrhenius correlation is compared with ten available empirical correlations in the literature. Our developed correlation presents the absolute average relative deviation (AARD) of 9.54% for predicting 316 experimental measurements. On the other hand, the most accurate correlation in the literature presents the AARD = 14.90% over the same database. Indeed, 56.2% accuracy improvement in the solubility prediction of the anti-cancer drugs in supercritical CO2 is the primary outcome of the current study

Use of mathematical methods in the resolution of chemical engineering problems

This thesis consists of a compendium of five works that illustrate the utilization of selected mathematical methods to solve specific chemical engineering problems. Hence, the thesis is intended to cover both, a review of fundamental mathematical procedures for the solution of models raised from chemical phenomena, and a demonstration of their effectiveness to obtain useful novel significant results. The opening paper explores diverse global optimization algorithms to adjust both kinetic constants and the binary interaction parameters (BIPs) for the Peng-Robinson equation of state to the experimental data. Those parameters are essential to determine the model raised from the supercritical transesterification of triolein with methanol to produce biodiesel, with CO2 as cosolvent, consisting of three reversible reaction in series. Here, a novel model merging the ordinary differential equations system raised from kinetic mechanism and the time-dependent thermodynamic state of the complex mixture is presented for diverse operating conditions. Among all results obtained, novel binary interaction coefficients for the intermediate reaction species (dioleins and monooleins) highlight. The second and fourth papers included in this thesis are aimed at the study of lanolin extraction from raw wool, using 5% ethanol in CO2. The former explores solid lanolin extraction under near-critical conditions by means of a mass-transfer model based on the shrinking-core concept, while the latter is addressed at the liquid lanolin supercritical extraction. Both models result in a partial differential equations (PDEs) system determined by the solubility of multiphasic lanolin, Henry-type partition coefficient and the lanolin mass transfer coefficient. Hence, in each paper the raised PDEs system is solved through a different method: in the second paper orthogonal collocation method is employed, while in the fourth paper finite differences method is used combined with the numerical integration of an expression previously obtained by means of the Laplace transform. Finally, an optimization procedure is used in order to fit the extraction parameters to the experimental data, achieving coherent results that agree well with those previously reported. Between the cases exposed, liquid lanolin extraction is significantly complex to model because of the diffusion phenomena that may occur inside the two lanolin fraction mixture added to the diffusion of solvent in the interphase. Therefore, in the third work a nonlinear autoregressive exogenous neural network model is designed to predict the outcoming extracted fraction of lanolin at diverse temperatures, pressures, solvent mass flow rates, wool packing densities and times. The problem with the scarce data available for training of the neural network is overcome by augmenting experimental data using an empirical Weibull function, which correctly predicts the lanolin breakthrough at the extractor exit. This hybrid Weibull - Neural Network algorithm results in a low prediction error and conform a powerful tool for optimizing operating conditions, proved by the fast convergence of genetic algorithm procedure. This thesis closes with Molecular Dynamics simulations for peptide-folding studies, followed by a Principal Component Analysis (PCA) and clustering analysis to understand the Free Energy Landscape of the peptide (FEL). Those methods are aimed at assessing the conformational profile of bombesin, a peptide with interest in drug design as a possible novel agonist and/or antagonist in the fight against cancer. Results suggest that the peptide adopts mainly helical structures at the C-terminus and, to a lesser extent, hairpin turn structures at the N-terminus. Those results agree with those available from NMR in a 2,2,2-trifluoroethanol/water (30% v/v), and point out a suitable a-helix conformation for binding where Trp8 and His12 interaction has a significant role.Aquesta tesi consta d'un compendi de cinc treballs que il·lustren la utilització de mètodes matemàtics per resoldre problemes específics d'enginyeria química. Per tant, la tesi està destinada a ser una revisió dels procediments matemàtics fonamentals per a la solució de models derivats de fenòmens químics i, a més, una demostració de la seva efectivitat per obtenir resultats útils i innovadors. L'article que obre la tesi explora diferents algoritmes d'optimització global per ajustar tant les constants cinètiques com el Paràmetres d'Interacció Binària (PIB) per a l'equació d'estat de Peng Robinsos a les dades experimentals. Aquests paràmetres són essencials per determinar el model derivat de la transesterificació supercrítica de la trioleïna amb metanol per produir biodièsel, amb CO2 com a cosolvent, que consisteix en tres reaccions reversibles en sèrie. Aquí, es presenta un nou model que fusiona el sistema d'EDOs derivat del mecanisme cinètic i l'estat termodinàmic de la barreja per a condicions de funcionament diverses. Entre tots els resultats obtinguts, destaquen els nous PIBs trobats per a les espècies de reacció intermèdies. El segon i quart treball inclosos en aquesta tesi estan destinats a l'estudi de l'extracció de lanolina de llana crua amb 5% d'etanol en CO2. El primer explora l'extracció de lanolina sòlida en condicions gairebé crítiques mitjançant un model de transferència de massa basat en el concepte del nucli minvant, mentre que el segon s'adreça al cas de l'extracció supercrítica de lanolina líquida. Ambdós models donen com a resultat un sistema d'EDPs determinat per la solubilitat de la lanolina multifàsica, el coeficient de partició de Henry i el coeficient de transferències de massa. Per tant, a cada article el sistema d'EDPs obtingut es resol mitjançant un mètode diferent: en el article s'utilitza un mètode de col·laboració ortogonal, mentre que en el quart s'utilitza el mètode de diferències finites combinat amb la integració numèrica d'una expressió obtinguda mitjançant la Transformada de Laplace. Finalment, es porta a terme una optimització per ajustar els paràmetres d'extracció a les dades experimentals, aconseguint resultats coherents que coincideixen amb els reportats anteriorment. Entre els casos expotsats, l'extracció de lanolina líquida és significativament complexa de modelar a causa dels fenòmens de difusió que es poden produir a l'interior de les dues fraccions de lanolina a més de la difusió del dissolvent en la interfase. Per tant, en el tercer treball es dissenya un model de xarxa neuronal exògena no lineal autoregressiva per predir la fracció extreta de lanlina a diverses temperatures, pressions, cabals de dissolvent, densitats d'empaquetament i temps. El problema derivat de l'escassetat de dades disponibles per a l'entrenament de la xarxa neuronal es supera amb l'augment d'aquestes mitjançant una funció de Weibull empírica, que prediu correctament l'avanç de la lanolina a la sortida de l'extractor. Aquest algoritme híbrid Weibull - xarxa neuronal resulta en un baix error de predicció i conforma una potent eina per optimitzar les condicions operatives, demostrada per la ràpida convergència de l'algoritme genètic utilitzat. Aquesta tesi tanca amb simulacions de Dinàmica Molecular per a l'estudi del plegament de pèptids seguint d'un Anàlisi de Components Principals (ACP) i del "clustering" per a l'anàlisi del Paisatge d'Energia Lliure (PEL). L'objectiu és avaluar el perfil conformacional de la bombesina, un pèptid amb interès en el disseny de fàrmacs com a possible nou agonista i/o antagonista en la lluita contra el càncer. Els resultats suggereixen que el pèptid adopta estructures helicoïdals principalment al extrem C, i també en menor mesura estructures de forquilla al extrem N. Aquests resultats coincideixen amb els disponibles de RMN en 2,2-trifluoroetanol/aigua (30% v/v) i indiquen una conformació d’hèlix a adequada per a la unió on la interacció Trp8 i His12 té un paper important

Modeliranje umjetne neuronske mreže višesustavnom dinamičkom adsorpcijom organskih onečišćujućih tvari na aktivnom ugljenu

The aim of this work was to model multi-system dynamic adsorption using an artificial intelligence technique. A set of data points, collected from scientific papers containing the dynamic adsorption kinetics on activated carbon, was used to build the artificial neural network (ANN). The studied parameters were molar mass, initial concentration, flow rate, bed height, particle diameter, BET surface area, average pore diameter, time, and concentration of dimensionless effluents. Results showed that the optimized ANN was obtained with a high correlation coefficient, R = 0.997, a root mean square error of RMSE = 0.029, and a mean absolute deviation of AAD (%) = 1.810 during the generalisation phase. Furthermore, a sensitivity analysis was also conducted using the inverse artificial neural network method to study the effect of all the inputs on the dynamic adsorption. Also in this work, the traceability of the estimated results was conducted by developing a graphical user interface. This work is licensed under a Creative Commons Attribution 4.0 International License.Cilj ovog rada bio je modelirati višesustavnu dinamičku adsorpciju tehnikom umjetne inteligencije. Za izradu umjetne neuronske mreže (ANN) upotrijebljen je skup podataka prikupljen iz znanstvenih radova koji sadrže kinetiku dinamičke adsorpcije na aktivnom ugljenu. Ispitivani parametri bili su: molarna masa, početna koncentracija, brzina protoka, visina sloja, promjer čestica, površina BET, prosječni promjer pora, vrijeme i koncentracija bezdimenzijskih otpadnih voda. Rezultati su pokazali da je tijekom faze generalizacije dobiven optimiran ANN s visokim koeficijentom korelacije, R = 0,997, korijenom srednje kvadratne pogreške RMSE = 0,029 i srednjim apsolutnim odstupanjem AAD (%) = 1,810. Dodatno, provedena je i analiza osjetljivosti primjenom metode inverzne umjetne neuronske mreže kako bi se proučio učinak svih ulaza na dinamičku adsorpciju. U radu je provedena i sljedivost procijenjenih rezultata razvojem grafičkog korisničkog sučelja. Ovo djelo je dano na korištenje pod licencom Creative Commons Imenovanje 4.0 međunarodna

ATHENA Research Book

The ATHENA European University is an alliance of nine Higher Education Institutions with the mission of fostering excellence in research and innovation by facilitating international cooperation. The ATHENA acronym stands for Advanced Technologies in Higher Education Alliance. The partner institutions are from France, Germany, Greece, Italy, Lithuania, Portugal, and Slovenia: the University of Orléans, the University of Siegen, the Hellenic Mediterranean University, the Niccolò Cusano University, the Vilnius Gediminas Technical University, the Polytechnic Institute of Porto, and the University of Maribor. In 2022 institutions from Poland and Spain joined the alliance: the Maria Curie-Skłodowska University and the University of Vigo. This research book presents a selection of the ATHENA university partners' research activities. It incorporates peer-reviewed original articles, reprints and student contributions. The ATHENA Research Book provides a platform that promotes joint and interdisciplinary research projects of both advanced and early-career researchers

Tracing back the source of contamination

From the time a contaminant is detected in an observation well, the question of where and when the contaminant was introduced in the aquifer needs an answer. Many techniques have been proposed to answer this question, but virtually all of them assume that the aquifer and its dynamics are perfectly known. This work discusses a new approach for the simultaneous identification of the contaminant source location and the spatial variability of hydraulic conductivity in an aquifer which has been validated on synthetic and laboratory experiments and which is in the process of being validated on a real aquifer

Book of abstracts of the 10th International Chemical and Biological Engineering Conference: CHEMPOR 2008

This book contains the extended abstracts presented at the 10th International Chemical and Biological Engineering Conference - CHEMPOR 2008, held in Braga, Portugal, over 3 days, from the 4th to the 6th of September, 2008. Previous editions took place in Lisboa (1975, 1889, 1998), Braga (1978), Póvoa de Varzim (1981), Coimbra (1985, 2005), Porto (1993), and Aveiro (2001). The conference was jointly organized by the University of Minho, “Ordem dos Engenheiros”, and the IBB - Institute for Biotechnology and Bioengineering with the usual support of the “Sociedade Portuguesa de Química” and, by the first time, of the “Sociedade Portuguesa de Biotecnologia”. Thirty years elapsed since CHEMPOR was held at the University of Minho, organized by T.R. Bott, D. Allen, A. Bridgwater, J.J.B. Romero, L.J.S. Soares and J.D.R.S. Pinheiro. We are fortunate to have Profs. Bott, Soares and Pinheiro in the Honor Committee of this 10th edition, under the high Patronage of his Excellency the President of the Portuguese Republic, Prof. Aníbal Cavaco Silva. The opening ceremony will confer Prof. Bott with a “Long Term Achievement” award acknowledging the important contribution Prof. Bott brought along more than 30 years to the development of the Chemical Engineering science, to the launch of CHEMPOR series and specially to the University of Minho. Prof. Bott’s inaugural lecture will address the importance of effective energy management in processing operations, particularly in the effectiveness of heat recovery and the associated reduction in greenhouse gas emission from combustion processes. The CHEMPOR series traditionally brings together both young and established researchers and end users to discuss recent developments in different areas of Chemical Engineering. The scope of this edition is broadening out by including the Biological Engineering research. One of the major core areas of the conference program is life quality, due to the importance that Chemical and Biological Engineering plays in this area. “Integration of Life Sciences & Engineering” and “Sustainable Process-Product Development through Green Chemistry” are two of the leading themes with papers addressing such important issues. This is complemented with additional leading themes including “Advancing the Chemical and Biological Engineering Fundamentals”, “Multi-Scale and/or Multi-Disciplinary Approach to Process-Product Innovation”, “Systematic Methods and Tools for Managing the Complexity”, and “Educating Chemical and Biological Engineers for Coming Challenges” which define the extended abstracts arrangements along this book. A total of 516 extended abstracts are included in the book, consisting of 7 invited lecturers, 15 keynote, 105 short oral presentations given in 5 parallel sessions, along with 6 slots for viewing 389 poster presentations. Full papers are jointly included in the companion Proceedings in CD-ROM. All papers have been reviewed and we are grateful to the members of scientific and organizing committees for their evaluations. It was an intensive task since 610 submitted abstracts from 45 countries were received. It has been an honor for us to contribute to setting up CHEMPOR 2008 during almost two years. We wish to thank the authors who have contributed to yield a high scientific standard to the program. We are thankful to the sponsors who have contributed decisively to this event. We also extend our gratefulness to all those who, through their dedicated efforts, have assisted us in this task. On behalf of the Scientific and Organizing Committees we wish you that together with an interesting reading, the scientific program and the social moments organized will be memorable for all.Fundação para a Ciência e a Tecnologia (FCT

ATHENA Research Book, Volume 1

The ATHENA European University is an alliance of nine Higher Education Institutions with the mission of fostering excellence in research and innovation by facilitating international cooperation. The ATHENA acronym stands for Advanced Technologies in Higher Education Alliance. The partner institutions are from France, Germany, Greece, Italy, Lithuania, Portugal, and Slovenia: the University of Orléans, the University of Siegen, the Hellenic Mediterranean University, the Niccolò Cusano University, the Vilnius Gediminas Technical University, the Polytechnic Institute of Porto, and the University of Maribor. In 2022 institutions from Poland and Spain joined the alliance: the Maria Curie-Skłodowska University and the University of Vigo. This research book presents a selection of the ATHENA university partners' research activities. It incorporates peer-reviewed original articles, reprints and student contributions. The ATHENA Research Book provides a platform that promotes joint and interdisciplinary research projects of both advanced and early-career researchers

Laboratory directed research and development. Annual report, fiscal year 1995

This document is a compilation of the several research and development programs having been performed at the Pacific Northwest National Laboratory for the fiscal year 1995

Predição da solubilidade de sólidos em CO2 supercrítico utilizando o modelo COSMO-SAC-Phi

A solubilidade de sólidos em dióxido de carbono supercrítico é uma informação importante para o projeto e otimização de processos nas indústrias alimentícia, farmacêutica e têxtil. O objetivo deste trabalho é investigar sistematicamente a precisão do modelo COSMO-SAC-Phi (CSP) em prever a solubilidade de sólidos em dióxido de carbono supercrítico. Os resultados obtidos através dos modelos PR + COSMOSAC EOS (PRCS), PSRK e Soave Redlich Kwong com a função alfa de Mathias Copeman com a clássica regra de mistura de Van der Waals (SRK-MC + vdW) foram comparados com o obtido através do modelo CSP. A solubilidade de 99 sólidos foi examinada. Uma grande variedade de compostos são considerados: ácidos alifáticos, álcoois alifáticos, hidrocarbonetos aromáticos, ácidos aromáticos, álcoois aromáticos, esteroides, estatinas e compostos aromáticos contendo átomos de nitrogênio, halogênio e/ou enxofre. A maioria destes compostos possuem moléculas semelhantes a fármacos. Um total de 2.450 pontos experimentais, cobrindo uma faixa de pressão de 45-500 bar e uma faixa de temperatura de 298-473 K, foram coletados para comparação com os resultados calculados. O banco de dados preditos para compostos puros Mol-Instincts foi usado para obter a pressão de saturação e o volume do líquido à pressão atmosfé- rica dos compostos estudados. A equação de estado CSP foi capaz de correlacionar os dados de pressão de saturação e volume do líquido com desvios médios de 5,32 % e 1,40 %, respectivamente. Com apenas dados de compostos puros, o CSP pôde predizer o equilíbrio sólido–fluido supercrítico das misturas. Quando a solubilidade calculada é comparada com dados experimentais, o desvio logarítmico médio da fração molar (ALDy) foi de 0,46 e 0,51 para as versões CSP (2021) e CSP (2019), respectivamente. Comparado aos modelos PSRK, PRCS e SRK-MC+vdW, a equação CSP (2021) teve um desempenho 27 %, 48 % e 64 % melhor, respectivamente, em termos de ALDy médio. Boas predições do ponto de cruzamento das isotermas de solubilidade foram também observadas. Isso indica que o modelo CSP pode fornecer uma primeira estimativa útil para a solubilidade, especialmente quando não há dados experimentais disponíveis.The solubility of solids in supercritical carbon dioxide is an important information for the design and optimization of processes in food, pharmaceutical and textile industries. The aim of this work is to systematically investigate the accuracy of COSMOSAC-Phi (CSP) model in predicting the solubility of solids in supercritical carbon dioxide. The results obtained through the PR + COSMOSAC EOS (PRCS), PSRK and Soave Redlich Kwong models with Mathias Copeman alpha function using the classic Van der Waals mixing rule (SRK-MC + vdW) were compared with those obtained from CSP model. The solubility of 99 solids was examined. A wide variety of compounds are considered, such as aliphatic acids, aliphatic alcohols, aromatic hydrocarbons, aromatic acids, aromatic alcohols, steroids, statins and aromatic compounds containing nitrogen, halogen and/or sulfur atoms, most of them are drug-like molecules. A total of 2450 experimental points covering a pressure range of 45-500 bar and a temperature range of 298-473 K obtained from the literature were compared with the calculated results. The Mol-Instincts database of predicted data from pure compounds was used to obtain the saturation pressure and the liquid volume at atmospheric pressure of the solids. The CSP equation of state was able to correlate the saturation pressure and the liquid volume at atmospheric pressure of the pure substances with average deviations of 5.32 % and 1.40 %, respectively. With only pure compound data, CSP could predict the behavior in mixture. When the calculated solubility is compared with experimental data, the average logarithmic deviation in molar fraction (ALDy) was 0.46 and 0.51 for the CSP (2021) and CSP (2019) versions, respectively. Compared to PSRK, PRCS and SRK-MC+vdW, the CSP (2021) model performed 27 %, 48 % and 64 % better, respectively, in terms of average ALDy. Good predictions of the crossover point of solubility isotherms were also observed. This indicates that the CSP model can provide a useful first estimate for solubility, especially when experimental data are not available