Farmacia y Tecnología Farmacéutica

URI permanente para esta comunidadhttps://hdl.handle.net/11441/11019

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3D Printed Fractal-like Structures with High Percentage of Drug for Zero-Order Colonic Release
(MDPI, 2022) Linares Blasco, Vicente; Aguilar de Leyva, Mercedes Ángela; Casas Delgado, Marta; Caraballo Rodríguez, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía
Colonic drug delivery of drugs is an area of great interest due to the need to treat high prevalence colonic local diseases as well as systemic conditions that may benefit from the advantages associated to this route of drug administration. In the last decade, the use of 3D printing technologies has expanded, offering the possibility of preparing personalized medicines in small batches directly at the point of care. The aim of this work is to design a high drug loaded 3D printed system prepared by a combination of Fused Deposition Modelling (FDM) and Injection Volume Filling (IVF) techniques intended for zero-order colonic drug release. For this purpose, different batches of binary and ternary filaments based on the thermoplastic polyurethane Tecoflex EG-72D (TPU), theophylline anhydrous (AT) as model drug, and magnesium stearate as lubricant have been developed and characterized. Filaments with the highest drug load and the best rheological properties were selected for the manufacture of a printed fractal-like structure based on multiple toroids. This design was proposed to provide high surface area, leading to increased drug release and water uptake in the colonic region. This structure was 3D printed by FDM and then coated in a unique step by IVF technology using the enteric polymer DrugCoat S 12.5. This way, an additional coating process is avoided, reducing costs and production time. Studies of drug release confirmed the ability of the structures to provide a five-hour period of constant drug delivery in the colonic region.
3D Printing DirePowder Extrusion in the Production of Drug Delivery Systems: State of the Art and Future Perspectives
(MDPI, 2024-03-22) Aguilar de Leyva, Mercedes Ángela; Casas Delgado, Marta; Ferrero Rodríguez, Carmen; Linares Blasco, Vicente; Caraballo Rodríguez, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Junta de Andalucía; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
The production of tailored, on-demand drug delivery systems has gained attention in pharmaceutical development over the last few years, thanks to the application of 3D printing technology in the pharmaceutical field. Recently, direct powder extrusion (DPE) has emerged among the extrusion-based additive manufacturing techniques. It is a one-step procedure that allows the direct processing of powdered formulations. The aim of this systematic literature review is to analyze the production of drug delivery systems using DPE. A total of 27 articles have been identified through scientific databases (Scopus, PubMed, and ScienceDirect). The main characteristics of the three types of 3D printers based on DPE have been discussed. The selection of polymers and auxiliary excipients, as well as the flowability of the powder mixture, the rheological properties of the molten material, and the printing temperatures have been identified as the main critical parameters for successful printing. A wide range of drug delivery systems with varied geometries and different drug release profiles intended for oral, buccal, parenteral, and transdermal routes have been produced. The ability of this technique to manufacture personalized, on-demand drug delivery systems has been proven. For all these reasons, its implementation in hospital settings in the near future seems promising.
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.
Development of 3D-Printed Bicompartmental Devices by Dual-Nozzle Fused Deposition Modeling (FDM) for Colon-Specific Drug Delivery.
(MDPI, 2023-09-21) Caraballo Rodríguez, Isidoro; Ferrero Rodríguez, Carmen; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Junta de Andalucía; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Dual-nozzle fused deposition modeling (FDM) is a 3D printing technique that allows for the simultaneous printing of two polymeric filaments and the design of complex geometries. Hence, hybrid formulations and structurally different sections can be combined into the same dosage form to achieve customized drug release kinetics. The objective of this study was to develop a novel bicompartmental device by dual-nozzle FDM for colon-specific drug delivery. Hydroxypropylmethylcellulose acetate succinate (HPMCAS) and polyvinyl alcohol (PVA) were selected as matrix-forming polymers of the outer pH-dependent and the inner water-soluble compartments, respectively. 5-Aminosalicylic acid (5-ASA) was selected as the model drug. Drug-free HPMCAS and drug-loaded PVA filaments suitable for FDM were extruded, and their properties were assessed by thermal, X-ray diffraction, microscopy, and texture analysis techniques. 5-ASA (20% w/w) remained mostly crystalline in the PVA matrix. Filaments were successfully printed into bicompartmental devices combining an outer cylindrical compartment and an inner spiral-shaped compartment that communicates with the external media through an opening. Scanning electron microscopy and X-ray tomography analysis were performed to guarantee the quality of the 3D-printed devices. In vitro drug release tests demonstrated a pH-responsive biphasic release pattern: a slow and sustained release period (pH values of 1.2 and 6.8) controlled by drug diffusion followed by a faster drug release phase (pH 7.4) governed by polymer relaxation/erosion. Overall, this research demonstrates the feasibility of the dual-nozzle FDM technique to obtain an innovative 3D-printed bicompartmental device for targeting 5-ASA to the colon.
Early stages of drug crystallization from amorphous solid dispersion via fractal analysis based on chemical imaging
(Elsevier, 2018-12) Abreu Villela, Renata; Schönenberger, Monica; Caraballo Rodríguez, Isidoro; Kuentz, Martin; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior. Brasil; Ministerio de Economía y Competitividad (MINECO). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Early stages of crystallization from amorphous solid dispersion (ASD) are typically not detected by means of standard methods like powder X-ray diffraction (XRPD). The aim of this study is therefore to evaluate if fractal analysis based on energy dispersive X-ray imaging can provide the means to identify early signs of physical instability. ASDs of the poorly water-soluble compound, felodipine (FEL) were prepared by solvent evaporation using different grades of HPMCAS, at 50 wt% drug loading. Samples were stored at accelerated conditions of 40 °C. Scanning electron microscopy equipped with an energy-dispersive X-ray spectroscopy (SEM-EDS) was used for elemental mapping of tablet surfaces. Comparative data were generated with a standard XRPD and with more sensitive methods for detection of early instability, i.e. laser scanning confocal microscopy (LSM) and atomic force microscopy (AFM). The SEM-EDS identified changes of drug-rich domains that were confirmed by LSM and AFM. Early changes in drug clusters were also revealed by a multifractal analysis that indicated a beginning phase separation and drug crystallization. Therefore, the presented fractal cluster analysis based on chemical imaging bears much promise as a new method to detect early signs of physical instability in ASD, which is of great relevance for pharmaceutical development.
Generation of a human iPS cell line (CABi003-A) from a patient with age-related macular degeneration carrying the CFH Y402H polymorphism
(Elsevier, 2019) García Delgado, Ana Belén; Calado, Sofía M.; Valdés Sánchez, Lourdes; Montero Sánchez, Adoración; Ponte-Zuñiga, Beatriz; De la Cerda, Berta; Bhattacharya, Shom Shanker; Díaz Corrales, Francisco Javier; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla. Departamento de Cirugía; Instituto de Salud Carlos III (ISCIII). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Age-related macular degeneration (AMD) is the leading cause of adult blindness in developed countries and is characterized by progressive degeneration of the macula, the central region of the retina. A human induced pluripotent stem cell (hiPSC) line was derived from peripheral blood mononuclear cells (PBMCs) from a patient with a clinical diagnosis of dry AMD carrying the CFH Y402H polymorphism. Sendai virus was using for reprogramming and the pluripotent and differ- entiation capacity of the cells were assessed by immunocytochemistry and RT-PCR.
Human neural stem cells for cell-based medicinal products
(Multidisciplinary Digital Publishing Institute (MDPI), 2021) Fernández Muñoz, Beatriz; García Delgado, Ana Belén; Arribas Arribas, Blanca; Sánchez Pernaute, Rosario; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Fundación Alicia Koplowitz; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Neural stem cells represent an attractive tool for the development of regenerative therapies and are being tested in clinical trials for several neurological disorders. Human neural stem cells can be isolated from the central nervous system or can be derived in vitro from pluripotent stem cells. Embryonic sources are ethically controversial and other sources are less well characterized and/or inefficient. Recently, isolation of NSC from the cerebrospinal fluid of patients with spina bifida and with intracerebroventricular hemorrhage has been reported. Direct reprogramming may become another alternative if genetic and phenotypic stability of the reprogrammed cells is ensured. Here, we discuss the advantages and disadvantages of available sources of neural stem cells for the production of cell-based therapies for clinical applications. We review available safety and efficacy clinical data and discuss scalability and quality control considerations for manufacturing clinical grade cell products for successful clinical application.
Redox-Responsive Polymersomes as Smart Doxorubicin Delivery Systems
(MDPI, 2022) Ferrero Rodríguez, Carmen; Casas Delgado, Marta; 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)
Stimuli-responsive polymersomes have emerged as smart drug delivery systems for programmed release of highly cytotoxic anticancer agents such as doxorubicin hydrochloride (Dox·HCl). Recently, a biodegradable redox-responsive triblock copolymer (mPEG–PDH–mPEG) was synthesized with a central hydrophobic block containing disulfide linkages and two hydrophilic segments of poly(ethylene glycol) methyl ether. Taking advantage of the self-assembly of this amphiphilic copolymer in aqueous solution, in the present investigation we introduce a solvent-exchange method that simultaneously achieves polymersome formation and drug loading in phosphate buffer saline (10 mM, pH 7.4). Blank and drug-loaded polymersomes (5 and 10 wt.% feeding ratios) were prepared and characterized for morphology, particle size, surface charge, encapsulation efficiency and drug release behavior. Spherical vesicles of uniform size (120–190 nm) and negative zeta potentials were obtained. Dox·HCl was encapsulated into polymersomes with a remarkably high efficiency (up to 98 wt.%). In vitro drug release studies demonstrated a prolonged and diffusion-driven release at physiological conditions (~34% after 48 h). Cleavage of the disulfide bonds in the presence of 50 mM glutathione (GSH) enhanced drug release (~77%) due to the contribution of the erosion mechanism. Therefore, the designed polymersomes are promising candidates for selective drug release in the reductive environment of cancer cells.
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.

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Examinando Farmacia y Tecnología Farmacéutica por Agencia financiadora "European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)"