Artículos (Farmacia y Tecnología Farmacéutica)

URI permanente para esta colecciónhttps://hdl.handle.net/11441/11020

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Amorphous Solid Dispersion of a Binary Formulation with Felodipine and HPMC for 3D Printed Floating Tablets
(Elsevier, 2024) Mora Castaño, Gloria; Millán Jiménez, Mónica; Niederquell, Andreas; Schonenberger, Monica; Shojaie, Fatemeh; Kuentz, Martin; Caraballo Rodríguez, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; Junta de Andalucía; Ministerio de Ciencia, Innovación y Universidades (MICINN). España
This study focuses on the combination of three-dimensional printing (3DP) and amorphous solid dispersion (ASD) technologies for the manufacturing of gastroretentive floating tablets. Employing hot melt extrusion (HME) and fused deposition modeling (FDM), the study investigates the development of drug-loaded filaments and 3D printed (3DP) tablets containing felodipine as model drug and hydroxypropyl methylcellulose (HPMC) as the polymeric carrier. Prior to fabrication, solubility parameter estimation and molecular dynamics simulations were applied to predict drug-polymer interactions, which are crucial for ASD formation. Physical bulk and surface characterization complemented the quality control of both drug-loaded filaments and 3DP tablets. The analysis confirmed a successful amorphous dispersion of felodipine within the polymeric matrix. Furthermore, the low infill percentage and enclosed design of the 3DP tablet allowed for obtaining low-density systems. This structure resulted in buoyancy during the entire drug release process until a complete dissolution of the 3DP tablets (more than 8 h) was attained. The particular design made it possible for a single polymer to achieve a zero-order controlled release of the drug, which is considered the ideal kinetics for a gastroretentive system. Accordingly, this study can be seen as an advancement in ASD formulation for 3DP technology within pharmaceutics.
Towards a rational basis for selection of excipients: Excipient Efficiency for controlled release
(Elsevier, 2015-10-15) Casas Delgado, Marta; Aguilar de Leyva, Mercedes Ángela; Caraballo Rodríguez, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Economía y Competitividad (MINECO). España
There are many factors influencing the drug release behaviour from a pharmaceutical formulation as the particle size of the drug and excipient, porosity of the system or geometrical phase transitions of the components. Therefore, the choice of the adequate excipient to achieve a specific drug release profile is mainly based on the experience and the trial and error method. Taking into account the directives towards the application of the “Quality by Design” approach, in this study the Excipient Efficiency (EE), a parameter able to quantify the capability of an excipient to control the drug release, has been developed. EE was initially calculated dividing the total porosity of the system by its diffusional release rate constant. The influence of several factors on this parameter has been evaluated. As a result, the final parameter has been corrected based on the drug solubility and the excipient particle size. EE provides a rational basis for identifying the most adequate excipients for a concrete formulation.
Release Behaviour of Clozapine Matrix Pellets Based on Percolation Theory
(Elsevier, 2011) Aguilar de Leyva, Mercedes Ángela; Sharkawi, Tahmer; Bataille, Bernard; Baylac, Gilles; Caraballo Rodríguez, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
The release behaviour of clozapine matrix pellets was studied in order to investigate if it is possible to explain it applying the concepts of percolation theory, previously used in the understanding of the release process of inert and hydrophilic matrix tablets. Thirteen batches of pellets with different proportions of clozapine/microcrystalline cellulose (MCC)/hydroxypropylmethyl cellulose (HPMC) and different clozapine particle size fractions were prepared by extrusion–spheronisation and the release profiles were studied. It has been observed that the distance to the excipient (HPMC) percolation threshold is important to control the release rate. Furthermore, the drug percolation threshold has a big influence in these systems. Batches very close to the drug percolation threshold, show a clear effect of the drug particle size in the release rate. However, this effect is much less evident when there is a bigger distance to the drug percolation threshold, so the release behaviour of clozapine matrix pellets is possible to be explained based on the percolation theory.
Study of the Critical Points and the Role of the Pores and Viscosity in Carbamazepine Hydrophilic Matrix Tablets
(Elsevier, 2012) Aguilar de Leyva, Mercedes Ángela; Cifuentes, Celia; Rajabi-Siahboomi, Ali R.; Caraballo Rodríguez, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
Percolation theory has been applied to estimate the Hypromellose (HPMC) percolation thresholds and the influence of the polymer viscosity and the initial porosity on these thresholds in carbamazepine multicomponent matrix formulations. Different batches containing two viscosity grades of HPMC as hydrophilic matrix forming polymer, MCC and lactose as fillers, and a lubricant mixture have been manufactured varying the compression pressure in order to obtain matrices with three levels of initial porosity. The results suggested the existence of an excipient percolation threshold between 13 and 15% v/v of HPMC for the different batches prepared. It has been found that the percolation threshold for this polymer is independent on the formulation factors studied in this paper: polymer viscosity and initial porosity of the matrices.
Development and Characterization of New Functionalized Polyurethanes for Sustained and Site-specific Drug Release in the Gastrointestinal Tract
(Elsevier, 2017) Campiñez, María Dolores; Benito Hernández, Elena María; Romero Azogil, Lucía; Aguilar de Leyva, Mercedes Ángela; García Martín, María de Gracia; Galbis Pérez, Juan Antonio; Caraballo Rodríguez, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Economía y Competitividad (MINECO). España; Junta de Andalucía
The main objective of the present paper has been the development and study of two new biodegradable polyurethanes, PU(dithiodiethanol-DTDI) and PU[(iPr)Man-DTDI], to be used as sustained matrix forming excipients. Furthermore, their capacity to act as excipient for colon drug delivery systems has been evaluated. Thus, SeDeM diagrams have been obtained to investigate their suitability to be processed through a direct compression process. Matrices containing 10–30% w/w of the polymers and theophylline anhydrous as model drug have been manufactured. Release studies have been carried out using a modified dissolution assay simulating pH and redox conditions for the gastro intestinal tract, including colon. Drug dissolution data have been analyzed according to the main kinetic models and their Excipient Efficiencies for prolonged release have been calculated. The principal parameters of the SeDeM Expert system, such as the parametric profile (mean radius) and the good compression index obtained for the polymers are above the values considered as adequate for direct compression even without addition of flow agents. The obtained values for Excipient Efficiency show good ability of the polymer to control the drug release. Finally, in the case of PU(dithiodiethanol-DTDI), a clear increase in the release rate has been observed when the formulation is subjected to colon simulating conditions.
Extrusion-based Technologies for 3D Printing: a Comparative Study of the Processability of Thermoplastic Polyurethane-based Formulations
(Taylor & Francis, 2023) Aguilar de Leyva, Mercedes Ángela; Linares Blasco, Vicente; Domínguez Robles, Juan; Casas Delgado, Marta; Caraballo Rodríguez, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Ministerio de Ciencia e Innovación (MICIN). España
Thermoplastic polyurethanes (TPU) offer excellent properties for a wide range of dosage forms. These polymers have been successfully utilized in personalized medicine production using fused deposition modeling (FDM) 3D printing (3DP). However, direct powder extrusion (DPE) has been introduced recently as a challenging technique since it eliminates filament production before 3DP, reducing thermal stress, production time, and costs. This study compares DPE and single-screw extrusion for binary (drug-TPU) and ternary (drug-TPU-magnesium stearate [MS]) mixtures containing from 20 to 60% w/w of theophylline. Powder flow, mechanical properties, fractal analysis, and percolation theory were utilized to analyze critical properties of the extrudates. All the mixtures could be processed at a temperature range between 130 and 160 °C. Extrudates containing up to 50% w/w of drug (up to 30% w/w of drug in the case of single-screw extrusion binary filaments) showed toughness values above the critical threshold of 80 kg/mm2. MS improved flow in mixtures where the drug is the only percolating component, reduced until 25 °C the DPE temperature and decreased the extrudate roughness in high drug content systems. The potential of DPE as an efficient one-step additive manufacturing technique in healthcare environments to produce TPU-based tailored on-demand medicines has been demonstrated.
Design Space and Critical Points in Solid Dosage Forms
(Elsevier, 2017) Aguilar de Leyva, Mercedes Ángela; Campiñez, María Dolores; Casas Delgado, Marta; Caraballo Rodríguez, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Economía y Competitividad (MINECO). España; Junta de Andalucía
The current regulatory environment based on the ICH guidelines encourages a systematic and science-based approach in the pharmaceutical development, required by the “Quality by design” concept. This methodology implies that the quality of a product must be designed instead of assayed in the final dosage form. For this purpose, a deep knowledge of the factors affecting the quality of the product is needed to establish the design space. This design space is limited by critical points of the formulation whose knowledge is essential in order to develop a robust dosage form. This papers deals with the main critical points that must be taken into account in the design of solid dosage forms such as inert and hydrophilic matrices as well as controlled released systems based in new biopolymers. The influence of factors such as the particle size or the rheology of powders in these critical points has been analysed. Moreover, in silico simulation software has been employed to elucidate the release mechanism leading to unexpectedly low critical points in sustained release matrices prepared with two new polyurethanes.
Study of the Critical Points in Combined Matrix Tablets Containing Both Inert and Swelling Excipients
(Elsevier, 2019) Aguilar de Leyva, Mercedes Ángela; Campiñez, Maria Dolores; Jost, Flavia; Gavira, Miguel; Caraballo Rodríguez, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Economía y Competitividad (MINECO). España
This work estimates for the first time critical points in combined matrices containing varying concentrations of the hydrophilic polymer Hydroxypropyl methylcellulose (HPMC) K100 M CR in presence of a constant percentage of the inert matrix forming polymer Eudragit RS-PO as well as varying concentrations of the inert polymer in presence of a constant percentage of the hydrophilic excipient. Drug release assays, water uptake studies and calculation of the Exicipient Efficiency (EE) have been carried out to study the interaction between the polymers. Surprisingly, an increase in the drug release rate occurs as the percentage of the hydrophobic polymer increases in the formulations. This fact is supported by the EE values which indicate a negative interaction between the two excipients. Moreover the HPMC percolation threshold estimated is higher than the one observed in pure HPMC matrices. It can be concluded that the HPMC creates pores in the inert skeleton, destabilizing the system. Moreover, the inert excipient destabilizes the gel layer formed by HPMC, changing its critical point. This information is essential for a rational estimation of the Design Space of a formulation and provides new knowledge on the behavior of the polymers in combined matrices, which contributes to the science based design.
Microneedle array-based electrochemical sensor functionalized with SWCNTs for the highly sensitive monitoring of MDMA in interstitial fluid
(Elsevier, 2023-10) Drăgan, Ana Maria; Parrilla, Marc; Cambré, Sofie; Domínguez Robles, Juan; Detamornrat, Usanee; Donnelly, Ryan F.; Oprean, Radu; Cristea, Cecilia; De Wael, Karolien; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; European Union (UE); Engineering and Physical Sciences Research Council (UK); Fund for Scientific Research (FWO). Belgium; Ministerio de Ciencia e Innovación (MICIN). España
Illicit drug consumption constitutes a great concern worldwide due to its increased spread and abuse, and the negative consequences exerted on society. For instance, 3,4-methylenedioxymethamphetamine (MDMA), a synthetic amphetamine-type substance, was abused by 20 million people worldwide in 2020. This psychoactive substance exerts a myriad of effects on the human body being dangerous for the consumer’s health. Besides, MDMA has been used in the treatment of some psychiatric conditions. Therefore, the development of wearable devices for MDMA sensing in biological fluids is of great importance for forensic toxicology (e.g., monitoring of patients with suspected or known MDMA consumption) as well as for therapeutic management of patients. Herein, we report the development of a wearable electrochemical platform based on a hollow microneedle (MN) array sensor for the monitoring of MDMA in the interstitial fluid by square-wave voltammetry. First, the holes of the MN array were modified with conductive pastes to devise a MN patch with a three-electrode system. Subsequently, the functionalization of the working electrode with nanomaterials enhanced MDMA detection. Thereafter, analytical parameters were evaluated exhibiting a slope of 0.05 µA µM−1 within a linear range from 1 to 50 µM and a limit of detection of 0.75 µM in artificial interstitial fluid. Importantly, critical parameters such as selectivity, piercing capability, temperature, reversibility and stability were assessed. Overall, the obtained MN sensor exhibited excellent analytical performance, making it a promising tool for MDMA tracking in interstitial fluid for individuals on probation or under therapeutic treatment.
From Extraction to Stabilization: Employing a 22 Experimental Design in Developing Nutraceutical-Grade Bixin from Bixa orellana L.
(Multidisciplinary Digital Publishing Institute, 2024-05-23) Luna-Finkler, Christine L.; Gomes, Aralí da C.; de Aguiar Júnior, Francisco C. A.; Ribeiro, Ester; Melo Barbosa, Raquel de; Severino, Patricia; Santini, Antonello; Souto, Eliana B.; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
Bixin is the main carotenoid found in the outer portion of the seeds of Bixa orellana L., commercially known as annatto. This compound is industrially employed in pharmaceutical, cosmetic, and food formulations as a natural dye to replace chemical additives. This study aimed to extract bixin from annatto seeds and obtain encapsulated bixin in a powder form, using freeze-drying encapsulation and maltodextrin as encapsulating agent. Bixin was extracted from annatto seeds employing successive washing with organic solvents, specifically hexane and methanol (1:1 v/v), followed by ethyl acetate and dichloromethane for subsequent washes, to effectively remove impurities and enhance bixin purity, and subsequent purification by crystallization, reaching 1.5 ± 0.2% yield (or approximately 15 mg of bixin per gram of seeds). Bixin was analyzed spectrophotometrically in different organic solvents (ethanol, isopropyl alcohol, dimethylsulfoxide, chloroform, hexane), and the solvents chosen were chloroform (used to solubilize bixin during microencapsulation) and hexane (used for spectrophotometric determination of bixin). Bixin was encapsulated according to a 22 experimental design to investigate the influence of the concentration of maltodextrin (20 to 40%) and bixin-to-matrix ratio (1:20 to 1:40) on the encapsulation efficiency (EE%) and solubility of the encapsulated powder. Higher encapsulation efficiency was obtained at a maltodextrin concentration of 40% w/v and a bixin/maltodextrin ratio of 1:20, while higher solubility was observed at a maltodextrin concentration of 20% w/v for the same bixin/maltodextrin ratio. The encapsulation of this carotenoid by means of freeze-drying is thus recognized as an innovative and promising approach to improve its stability for further processing in pharmaceutical and food applications.
Microneedle Array-based Electrochemical Sensor Functionalized with SWCNTs for the Highly Sensitive Monitoring of MDMA in Interstitial Fluid
(Elsevier, 2023) Drăgan, Ana Maria; Parrilla, Marc; Cambré, Sofie; Domínguez Robles, Juan; Detamornrat, Usanee; Donnelly, Ryan F.; Oprean, Radu; Cristea, Cecilia; De Wael, Karolien; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; European Union (UE). H2020; Engineering and Physical Sciences Research Council (UK); Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca; Research Foundation Flanders (FWO); Ministerio de Ciencia e Innovación (MICIN). España
Illicit drug consumption constitutes a great concern worldwide due to its increased spread and abuse, and the negative consequences exerted on society. For instance, 3,4-methylenedioxymethamphetamine (MDMA), a synthetic amphetamine-type substance, was abused by 20 million people worldwide in 2020. This psychoactive substance exerts a myriad of effects on the human body being dangerous for the consumer’s health. Besides, MDMA has been used in the treatment of some psychiatric conditions. Therefore, the development of wearable devices for MDMA sensing in biological fluids is of great importance for forensic toxicology (e.g., monitoring of patients with suspected or known MDMA consumption) as well as for therapeutic management of patients. Herein, we report the development of a wearable electrochemical platform based on a hollow microneedle (MN) array sensor for the monitoring of MDMA in the interstitial fluid by square-wave voltammetry. First, the holes of the MN array were modified with conductive pastes to devise a MN patch with a three-electrode system. Subsequently, the functionalization of the working electrode with nanomaterials enhanced MDMA detection. Thereafter, analytical parameters were evaluated exhibiting a slope of 0.05 µA µM−1 within a linear range from 1 to 50 µM and a limit of detection of 0.75 µM in artificial interstitial fluid. Importantly, critical parameters such as selectivity, piercing capability, temperature, reversibility and stability were assessed. Overall, the obtained MN sensor exhibited excellent analytical performance, making it a promising tool for MDMA tracking in interstitial fluid for individuals on probation or under therapeutic treatment.
La gamificación como herramienta para el aprendizaje de excipientes farmacéuticos
(Dykinson, 2023) Cayero Otero, María Dolores; Durán Lobato, María Matilde; Álvarez Fuentes, Josefa; Martín Banderas, Lucía; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
Servicios farmacéuticos en la era digital: el rol de las tecnologías de la información y comunicación (TICs)
(Real e Ilustre Colegio de Farmacéuticos de Sevilla, 2022) Ojeda Casares, Manuel; Pérez Fernández, Manuel; Rabasco Álvarez, Antonio María; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
Some Asian Women Pioneers of Chemistry and Pharmacy
(MDPI, 2022) Nuñez Valdés, Juan; Pablos Pons, Fernando de; Ramos Carrillo, Antonio; Universidad de Sevilla. Departamento de Geometría y Topología; Universidad de Sevilla. Departamento de Química Analítica; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
At present, several countries on the Asian continent are still very closed off to the idea of allowing not only the work of women, but also even the fact that they can study university degrees and, after finishing them, go on to practice their professions. In addition, if we go back to the beginning of the 20th century, this situation was even more serious. However, this was not an impediment for some women from these countries to achieve their goals of pursuing higher education and then serving society with their work. This article is dedicated to showing the biographies of three of them, the Indian chemist Asima Chatterjee and Philippine pharmacists Matilde S. Arquiza and Filomena Francisco. The most relevant features of their personal and professional lives are presented and previous biographies about them are completed. The main objective of this work is to show these figures to society and hold them up as references to other people, and the methodology followed has been the search for data about their lives and work that would allow us to complete the previous existing biographies about them. A brief biography on Janaki Ammal, the first Indian woman to obtain a doctorate, is also included.
Comparison of Synthetic Pathways for Obtaining Fluorescent Nanomaterials Based on Halloysite and Carbon Dots for Potential Biological Sensing
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-05-14) Massaro, Marina; Cinà, Giuseppe; Cavallaro, Giuseppe; Lazzara, Giuseppe; Silvestri, Alessandro; Melo Barbosa, Raquel de; Sánchez Espejo, Rita; Viseras Iborra, César; Notarbartolo, Monica; Riela, Serena; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
Recently, fluorescent sensors have gained considerable attention due to their high sensitivity, low cost and noninvasiveness. Among the different materials that can be used for this purpose, carbon dots (CDs) represent valuable candidates for applications in sensing. These, indeed, are easily synthesized, show high quantum yield and are highly biocompatible. However, it was pointed out that the photoluminescence properties of these nanomaterials are strictly dependent on the synthetic and purification methods adopted. The presence of halloysite nanotubes (HNTs), a natural, low cost and biocompatible clay mineral, has been found to be efficient in obtaining small and highly monodispersed CDs without long and tedious purification techniques. Herein, we report the comparison of synthetic pathways for obtaining halloysite-N-doped CDs (HNTs-NCDs) that could be used in biological sensing. One was based on the synthesis of N-doped CDs by a bottom-up approach on HNTs’ surface by a MW pyrolysis process; the other one was based on the post-modification of pristine N-doped CDs with halloysite derivatives. The evaluation of the best synthetic route was performed by different physico-chemical techniques. It was found that the bottom-up approach led to the formation of N-doped CDs with different functional groups onto the HNTs’ surface. This evidence was also translated in the different fluorescence quantum yields and the existence of several functional groups in the obtained materials was investigated by potentiometric titrations. Furthermore, the ability of the synthesized nanomaterials as sensors for Fe3+ ions detection was assessed by spectroscopic measurements, and the cellular uptake was verified by confocal/fluorescence microscopies as well.
Dietary oleacein, a secoiridoid from extra virgin olive oil, prevents collagen-induced arthritis in mice
(ROYAL SOC CHEMISTRY, 2024) Rosillo Ramírez, María de los Ángeles; Villegas Lama, Isabel; Vázquez Román, María Victoria; Fernández-Santos, José María; Ortega Vidal, Juan; Salido, Sofía; González Rodríguez, María Luisa; Alarcón de la Lastra Romero, Catalina; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla. Departamento de Farmacología; Junta de Andalucía
Olacein (OLA), one of the main secoiridoids derived from extra virgin olive oil (EVOO), has been shown to modulate oxidative and inflammatory responses in various pathological conditions; however, its potential benefit in joint disorders such as rheumatoid arthritis (RA) is unknown. Therefore, this study was designed to evaluate the preventive role of the effects of an OLA-supplemented diet in the murine model of collagen-induced arthritis (CIA), delving into the possible mechanisms and signaling pathways involved. Animals were fed an OLA-enriched preventive diet for 6 weeks prior to CIA induction and until the end of the experimental time course. On day 43 after the first immunization, mice were sacrificed: blood was collected, and paws were histologically and biochemically processed. Dietary OLA prevented collageninduced rheumatic bone, joint and cartilage conditions. Circulating matrix metalloproteinase (MMP)-3 and proinflammatory cytokine (IL-6, IL-1β, TNF-α, IL-17) levels were significantly decreased in the joint, as well as MMP-9 and cathepsin-K (CatK) expression in secoiridoid-fed animals. In addition, dietary OLA was able to decrease COX-2, mPGES-1 and iNOS protein expressions and, also, PGE2 levels. The mechanisms possibly involved in these protective effects could be related to the activation of the Nrf-2/HO-1 axis and the inhibition of proinflammatory signaling pathways, including JAK-STAT, MAPKs and NF-κB, involved in the production of inflammatory and oxidative mediators. These results support the interest of OLA, as a nutraceutical intervention, in the management of RA.
Estudio tecnofarmacéutico de los Anticuerpos Conjugados a Fármacos comercializados en España
(Universidad Granada, 2024) Borrego Higueras, Elena; Ginés Dorado, Juan Manuel; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
Introducción: el tratamiento del cáncer supone uno de los grandes desafíos a los que se enfrenta la sociedad científica actual. En esta lucha sanitaria, se desarrollan los anticuerpos conjugados a fármacos, capaces de lograr la muerte celular mediante el transporte y liberación de compuestos citotóxicos selectivamente sobre células tumorales. Se componen de un anticuerpo monoclonal (de naturaleza proteica) unido a un fármaco citotóxico (de carácter lipófilo) mediante un enlazador. Las formulaciones se han de diseñar para mantener dicha unión durante su almacenamiento y administración. Objetivo: identificar los medicamentos comercializados en España cuyo principio activo es un anticuerpo conjugado a fármaco, estudiando diferentes aspectos tecnofarmacéuticos, en especial los componentes de sus formulaciones. Método: dado que este tipo de medicamento pertenece al grupo ATC L01F, han sido identificados a través del buscador de la Agencia Española de Medicamentos y Productos Sanitarios. La consulta de sus fichas técnicas, artículos de revisión e investigación relacionados con el tema así como el Handbook of Pharmaceuticals Excipients, ha permitido realizar el estudio tecnofarmacéutico. Resultados: se han analizado distintos aspectos tecnofarmacéuticos: forma farmacéutica, vía de administración, conservación y, en especial, sus formulaciones. Se ha estudiado en profundidad la naturaleza del principio activo y los requisitos de las formulaciones en base a sus características. Conclusiones: los ocho anticuerpos conjugados a fármacos aprobados en España se presentan en forma de polvo liofilizado en vial que se deben almacenar entre 2-8 ºC. Para su administración, se reconstituyen obteniéndose inicialmente un concentrado, que posteriormente se diluye y administra en forma de perfusión intravenosa o goteo. Su formulación tipo incluye un lioprotector, un antiagregante, un regulador del pH y eventualmente antioxidantes o reductores de la viscosidad.
Application of ultrasound-assisted compression and 3D-printing semi-solid extrusion techniques to the development of sustained-release drug delivery systems based on a novel biodegradable aliphatic copolyester
(Elsevier, 2024) Ferrero Rodríguez, Carmen; Urpí, Lourdes; Aguilar de Leyva, Mercedes Ángela; Mora Castaño, Gloria; Linares Blasco, Vicente; Millán Jiménez, Mónica; Martínez de Ilarduya, Antxon; Caraballo Rodríguez, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
The purpose of this study was to investigate the ability of two advanced hot-processing technologies, Ultrasound-Assisted Compression (USAC) and 3D-printing Semi-solid Extrusion (SSE), to manufacture sustained-release drug delivery systems based on a novel biodegradable aliphatic copolyester. The copolymer was synthesized from ω-pentadecalactone (PDL), 1,4-cyclohexanedimethanol (CHDM) and dimethyl succinate (DMS) (monomer ratio PDL/CHDM/DMS 70/30/30) by enzymatic ring opening polymerization and two-step melt polycondensation processes and has a random microstructure, a high molecular weight (107,100 g mol -1) and a relatively low melting point (~65 ◦C). The antibacterial agent metronidazole (MTZ) was chosen as model drug and binary physical mixtures copolymer:drug were prepared at 90:10 and 70:30 w/w ratios. Thermal analysis studies evidenced that the formulations could be processed below their degradation temperatures. Drug delivery devices with dense and meshed structures were manufactured using USAC and SSE techniques, respectively, with USAC devices exhibiting more reproducible physical properties than the SSE systems. Powder X-ray diffraction and scanning electron microscopy studies showed a partial sintering of the copolyester during USAC processing while MTZ remained mostly crystalline. In contrast, the copolymer melted and the drug underwent some amorphization when processed using SSE. In vitro drug release studies in phosphate buffer (pH 6.8) showed that, after an initial burst release of metronidazole, USAC and SSE devices exhibited a prolonged and/or sustained drug release over 20 days. The initial burst release was dependent on the manufacturing technique and the drug/polymer ratio, being minimized for SSE devices containing 10 wt% MTZ. The whole drug release profiles fitted well to the Peppas-Sahlin model, being drug diffusion the predominant release mechanism. After the burst release, the sustained release period of USAC and SSE devices containing 10 wt% MTZ showed a good fit to the zero-order kinetic model, with faster drug release from the SSE devices due to the larger surface area of their meshed structure. In conclusion, this work demonstrates that processing the aliphatic copolyester by both USAC and SSE technologies provides an attractive strategy to manufacture biodegradable drug delivery systems for long-term release of metronidazole.
Surface modification of titanium foams for modulated and targeted release of drug-loaded biocompatible hydrogel. Proof of concept
(Elsevier, 2024-05) Mehdi-Sefiani, Hanaa; Pérez-Puyana, Víctor Manuel; Sepúlveda Ferrer, Ranier Enrique; Romero García, Alberto; Domínguez Robles, Juan; Chicardi Augusto, Ernesto; Universidad de Sevilla. Departamento de Ingeniería Química; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla. Departamento de Ingeniería y Ciencia de los Materiales y del Transporte; Ministerio de Ciencia e Innovación (MICIN). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); European Commission. Fondo Social Europeo (FSO); Junta de Andalucía; Universidad de Sevilla. TEP229: Tecnología y Diseño de Productos Multicomponentes; Universidad de Sevilla. CTS547: Caracterización y Optimización Estadística de Medicamentos; Universidad de Sevilla. TEP973: Tecnología de Polvos y Corrosión
Bone-tissue replacement surgeries usually need medication to mitigate implant rejections or prevent local infections. In this study, a modulated and targeted tetracycline (TC) loaded gelatine type A hydrogel is release from Ti foams as a proof of concept for an innovative and intelligent drug release system. The drugs are released in a localized and controlled manner. The Ti foams fabricated by the space holder technique were surface modified by two different techniques of surface modification, i.e., thermal oxidation and acid etching, to assess their influence on TC release. The characterization carried out after the surface modification indicated that samples modified with acid etching have produced a rougher surface, increasing the diameter of pores (from 500 μm to 700 μm, approximately) due to coalescence of pores. The increase of pore roughness has demonstrated the delaying of the TC release due to the greater adhesion between the surface roughness and the hydrogel. In addition, the increase of pore size improves the possibility to infiltrate high amount of drug-loaded biocompatible hydrogel. Opposite, oxidized surface samples have generated a rutile type TiO₂ layer that, because of its hydrophilic nature facilitate the degradation of the hydrogel, and consequently, the TC release from the Ti foams. Therefore, both methods show opposite behaviour, available to increase (acid etching) or decrease (thermal oxidation) the TC release thanks to the different kinetic degradation of hydrogel, as a potential way for drug-release from metallic implants. Thus, while acid-etched samples showed maximum TC release value of 35 wt%, after 120 min, the oxidized samples surpassed the 40 % of TC release after same 120 min of release time treatment.
Gertrude Belle Elion, Chemist and Pharmacologist, Discoverer of Highly Relevant Active Substances
(MDPI, 2022-05) Núñez Valdés, Juan; Pablos Pons, Fernando de; Ramos Carrillo, Antonio; Universidad de Sevilla. Departamento de Geometría y Topología; Universidad de Sevilla. Departamento de Química Analítica; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla. FQM347: Análisis Aplicado; Universidad de Sevilla. HUM371: Andalucía y América Latina: Fronteras Oceánicas, Redes Sociales, Ciudad y Territorio
Gertrude Belle Elion was a woman who had to overcome many difficulties to achieve her dream of studying to be able to cure illnesses, especially those of the heart. These difficulties were imposed both by the limited economic resources of herself and her family, which did not allow her to pay the academic fees of the university in which she wanted to enroll, as well as gender, since she also had to fight against inequalities of that type prevalent in the society of her time. However, and despite these obstacles, she managed to graduate in Chemistry, based on interest, effort and tenacity, and later began a research career full of successes, which led her to discover relevant active substances which allow her to be awarded the Nobel Prize in Physiology or Medicine in 1988. This article presents the most relevant features of her personal and professional life and completes previous biographies about her life. Its main objective is to reintroduce her to society and put her as a reference to other people. The methodology followed has been the search for those data about her life and work that would allow completing the previous existing biographies about her.

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