Mechanochemical synthesis of a novel eutectic of the antimicrobial nitazoxanide with improved dissolution performance

Nitazoxanide (NTZ) is a broad spectrum antimicrobial agent with poor aqueous solubility and low bioavailability. Thus, the generation of new solid forms of NTZ is relevant to improve its unfavorable properties. The present study deals with the application of mechanochemistry for the preparation of alternate solid forms of NTZ, using saccharine (SAC) as coformer. Methods: NTZ-SAC mixtures were prepared by neat and liquid-assisted grinding (LAG) and characterized using differential scanning calorimetry (DSC), hot stage microscopy (HSM), X-ray Powder Diffraction (XRPD), 13C Solid-state Nuclear Magnetic Resonance (SSNMR) and Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectroscopy. Powder dissolution (PD) profiles were obtained with USP apparatus 2 in buffer phosphate pH 6.5 with 0.25% TweenÒ 80 - 0.25% triethanolamine and in 0.25% sodium lauryl sulfate, at 37 ºC ± 0.5 ºC and 75 rpm. Drug release was characterized in terms of dissolution efficiency (DE). Results: XRPD, SSNMR and DRIFT indicated that NTZ and SAC did not cocrystallize but DSC and HSM revealed that they formed a binary eutectic mixture which melted near 176 °C, a melting temperature lower than those of NTZ and SAC. PD data indicated that the 1:1 NTZ-SAC sample obtained by LAG exhibited a slightly higher DE than pure NTZ in the two assayed media. Conclusion: NTZ and SAC formed a eutectic, the first reported for this drug, which improved its dissolution rate and opened the pathway for studies searching for new eutectics with better biopharmaceutical attributes than NTZ and the NTZ-SAC eutectic reported herein.Fil: Fandiño, Octavio Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaFil: Bruno, Flavia Paola. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monti, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Sperandeo, Norma Rebeca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentin

Modificación de formas farmacéuticas sólidas: relevamiento en un hospital de la provincia de Córdoba

Introducción: La modificación de formas farmacéuticas (FF) sólidas (comprimidos y cápsulas) es una práctica común en el ámbito hospitalario. Esta práctica puede afectar a sus características fisicoquímicas y biofarmacéuticas, al efecto farmacológico y a veces provocar la aparición de efectos secundarios indeseables. Objetivos: Identificar los medicamentos cuya FF es modificada en un Hospital de Córdoba (Argentina), la manera en que dichas modificaciones son efectuadas y establecer si las mismas eran procedentes o no. Métodos: Se analizaron retrospectivamente las prescripciones efectuadas entre el 5 y 11 de mayo de 2012 y se identificaron las que solicitaban alteración de la FF. Se realizaron entrevistas abiertas a enfermeros y visitas a cada servicio del hospital para determinar cómo se modificaban las FF. Resultados: Se analizaron 700 prescripciones correspondientes a 113 pacientes. A 61 pacientes (54 %) se les modificó la FF (49 por indicación médica; 7 porque tenían sonda nasogástrica, 3 por decisión del paciente y 2 por decisión de enfermería). A 23 de los medicamentos prescriptos se les manipuló la FF, pero solo 12 de ellos fueron correctamente manipulados. Las principales modificaciones fueron la división de comprimidos y la pulverización-dispersión en agua de comprimidos y cápsulas. Conclusión: La FF de varios medicamentos es alterada en el hospital analizado, muchas veces sin indicación médica y sin justificación científica. Sería adecuado realizar cursos formativos y establecer una colaboración más estrecha entre Farmacia y las Unidades de Enfermería del hospital investigado.Background: In the hospital setting is frequent to manipulate solid dosage forms (SDF, tablets 16and capsules), which can affect their physicochemical and biopharmaceutical properties, the pharmacoloeffect and sometimes to cause the appearance of undesirable side effects. Objectives: To identify the medicines whose SDF is altered in a Hospital of Cordoba (Argentina), to determine how these modifications are made and to establish whether they were properly performed or not. Methods: We retrospectively analyzed the prescriptions made between the 5th and the 11th of March of 2012 and identified impaired requesting SDF modifications. Open interviews were held with nurses and service visits to each hospital to determine how they manipulated the SDF. Results: We analyzed 700 prescriptions for 113 patients, of which 61 (54%) had manipulations of the received SDF (49 for medical prescription, 7 because they had nasogastric tubes, 3 due to patient choice and 2 by nursing decision). Twenty three medicines were manipulated, but only 12 were correctly manipulated. The major changes were partition of tablets and grinding of tablets or microgranules and dispersible in water. Conclusion: The SDF of several medicines is altered in the analyzed hospital, many times without medical indication and scientific justification. It would be appropriate to conduct training courses and establish closer collaborations between pharmacy and nursing units in the investigated hospital.Fil: Parisia, Luciana R.. Provincia de Córdoba. Hospital J. B. Iturraspe; ArgentinaFil: Olivera, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Sperandeo, Norma Rebeca. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentin

Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide

Nitazoxanide [2-(acetyloxy)-N-(5-nitro-2-thiazolyl)benzamide, NTZ] is a potent antiparasitic and antiviral agent recently approved. The anti-protozoal activity of NTZ is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme dependent electron transfer reaction. As drug– enzyme interactions are governed by the three-dimensional stereochemistry of both participants, the crystal structure of NTZ was determined for the first time to identify the conformational preferences that may be related to biological activity. NTZ crystallizes as the carboxamide tautomer in the orthorhombic system, space group Pna21 with the following parameters at 100(2) K: a = 14.302(2) Å, b = 5.2800(8) Å, c = 33.183(5) Å, V = 2505.8(6) Å3 , Z = 8, Dx = 1.629 g cm3 , R = 0.0319, wR2 = 0.0799 for 5121 reflections. In addition, the spectroscopic and thermal properties were determined and related to the molecular structure. The 13C CPMAS NMR spectra showed resolved signals for each carbon of NTZ, some signals being broad due to residual dipolar interaction with quadrupolar 14N nuclei. In particular, the resonance at about 127 ppm showed multiplicity, indicating more than one molecule in the asymmetric unit and this is consistent with the crystallographic data. The DSC and TG data revealed that NTZ shows a single DSC melting peak with extrapolated onset at 201 C which is accompanied by a TG weight loss, indicating that NTZ melts with decomposition.Fil: Bruno, Flavia Paola. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Caira, Mino R.. University of Cape Town; SudáfricaFil: Monti, Gustavo Alberto. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Kassuha, Diego Enrique. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Sperandeo, Norma Rebeca. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentin

Elaboración de una tabla comparativa de usos y propiedades farmacocinéticas y farmacodinámicas de bloqueantes neuromusculares disponibles en un hospital público de Córdoba

Informe CIMEFil: Uema, Sonia Andrea Naeko. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas; Argentina.Fil: Sperandeo, Norma Rebeca Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas; Argentina.Fil: Dutto, Susana Córdoba. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital Misericordia. Servicio de Farmacia; Argentina.Fil: Suarez, Marina Eliana Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital Misericordia. Servicio de Farmacia; Argentina.Fil: Martini, Gabriela Magali Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital Misericordia. Servicio de Farmacia; Argentina.Relajación del músculo esquelético. Uso en Unidad de Terapia Intensiva (UTI), Quirófano Atracurio, pancuronio, rocuronio, succinilcolina, vecuronio. Problemas: alta rotación, sobre-stock, riesgo ruptura de stock, posible cambio proceso de compra. Necesidad de información actualizada para toma de decisiones.info:eu-repo/semantics/publishedVersionFil: Uema, Sonia Andrea Naeko. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas; Argentina.Fil: Sperandeo, Norma Rebeca Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas; Argentina.Fil: Dutto, Susana Córdoba. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital Misericordia. Servicio de Farmacia; Argentina.Fil: Suarez, Marina Eliana Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital Misericordia. Servicio de Farmacia; Argentina.Fil: Martini, Gabriela Magali Gobierno de la Provincia de Córdoba. Ministerio de Salud. Hospital Misericordia. Servicio de Farmacia; Argentina

Pharmaceutical polymorphism of a 5´-O-oxalatoyl prodrug of zidovudine (azidothymidine)

The importance of polymorphism in pharmaceuticals makes its study relevant. The aim of this study was to investigate the solid-state forms in which 3´-azido-2´,3´-dideoxi-5´-O-oxalatoyl-thymidinic acid (AZT-Ac), a zidovudine (AZT) prodrug with improved pharmacokinetic properties, may exist. Samples were prepared using different crystallization conditions, and characterized using powder X-ray diffraction, solid state nuclear magnetic resonance, differential scanning calorimetry, thermogravimetry and hot stage microscopy. Pharmaceutical relevant properties such as solid-state stability and intrinsic dissolution rate (IDR) at 37 °C in simulated gastric fluid (SGF) were also evaluated. AZT-Ac was found able to exist as a crystalline polymorph (AZT-Ac-C) and an amorphous phase (AZT-Ac-A), which were thoroughly characterized. At 40 °C/75% RH, AZT-Ac-A in part devitrified to AZT-Ac-C, and partially hydrolyzed to AZT after 7 and 14 days of storage, respectively. AZT-Ac-C was physically stable at 40 °C/75% RH but partly hydrolyzed to AZT after 14 days of storage. In SGF, AZT-Ac-C exhibited a linear ID profile and provided an ID rate of 0.494 mg/min/cm2 while AZT-Ac-A exhibited a nonlinear profile. Therefore, the crystalline form demonstrated advantages over the amorphous one in terms of solid state stability and IDR, but approaches to enhance its stability should be considered for further formulation of this prodrug.Fil: Kassuha, Diego Enrique. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Cs. de la Alimentación, Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bruno, Flavia Paola. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Laboratorio Fresenius Kabi; ArgentinaFil: Monti, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Sperandeo, Norma Rebeca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentin

Preparation and characterization of polymorphs of the glucocorticoid deflazacort

The polymorphism of new and old active pharmaceutical ingredients (APIs) is of great importance due to performance, stability and processability aspects. The objective of this study was to investigate the polymorphism of deflazacort (DEF), a glucocorticoid discovered >40 years ago, since this phenomenon has not been previously investigated for this API. Using different methods for solid form screening, it was determined for the first time that DEF is able to exist as three forms: a crystalline (DEF-1); a hydrated X-ray amorphous (DEF-t-bw) and an anhydrous amorphous phase (DEF-g) obtained from manually grinding DEF-1. The in vitro and in vivo dissolution rates (DRs) of DEF-1 and DEF-t-bw, which were measured using the rotating disk method in water at 37 °C and the pellet implantation technique in rats, respectively, indicated that DEF-t-bw exhibited slightly faster in vitro and in vivo DRs than those of the crystalline form, but the values were not significantly different. In addition, it was determined that DEF-t-bw devitrifies to DEF-1 by the effect of pressure, humidity and heat. It was concluded that DEF is glucorticoid with low tendency to exhibit different crystalline forms and that DEF-t-bw has no advantages over DEF-1 in terms of solubility, DRs and solid-state stability.Fil: Kassuha, Diego Enrique. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aiassa, Virginia. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bruno, Flavia Paola. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cuadra, Gabriel R.. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sperandeo, Norma Rebeca. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

X-ray, DFT, FTIR and thermal study of the antimicrobial N-benzenesulfonyl-1H-1,2,3-benzotriazole

N-benzenesulfonyl-1H-1,2,3-benzotriazole (NBSBZT) is a compound with significant trypanocidal and bactericidal activities, which we reported previously. In this work a combined experimental and theoretical study of its structural and molecular properties is communicated. The crystal structure of NBSBZT was determined by single crystal X-ray diffraction. The molecular vibrations and behavior on heating of NBSBZT were investigated by Fourier Transform Infrared (FTIR) Spectroscopy, Differential Scanning Calorimetry (DSC), Thermogravimetry (TG) and Hot Stage Microscopy (HSM). In parallel, Quantum Chemical calculations based on Density Functional Theory (DFT) and Scaled Quantum Mechanics methods were used to determine the geometrical, energetic and vibrational characteristics of NBSBZT. The study demonstrated that NBSBZT crystallized in the triclinic space group P‾1 (No. 2) with two inversion-related molecules in the unit cell (Z = 2). Its overall molecular conformation can be described by two torsion angles, namely φ1 (N2–N1–S10–C13) = −94.5(2)° and φ2 (N1–S10–C13–C14) = 84.2(2)°. The minimum energy structures found by theoretical calculations showed φ1 = −67.6° and φ2 = 88.0° in vacuum; however, in water, the torsion angles were −77.5° and 88.7° respectively. The differences in φ1 (Δφ1 solid state-vacuum = 26.9° and Δφ1 solid state-water = 17.0°) could be attributed to the high intermolecular cohesive forces present in the crystal of NBSBZT. A good correlation between the experimental and theoretical mid-FTIR spectra was found. The DSC, TG and HSM results indicated that NBSBZT was a solvent-free solid, which melted at 128.8 °C but decomposed above 130 °C.Fil: Komrovsky, Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaFil: Sperandeo, Norma Rebeca. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaFil: Vera, Domingo Mariano Adolfo. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; ArgentinaFil: Caira, Mino R.. University of Cape Town; SudáfricaFil: Mazzieri, Maria Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentin

Characterization and structural analysis of the potent antiparasitic and antiviral agent tizoxanide

Tizoxanide [2-(hydroxy)-N-(5-nitro-2-thiazolyl)benzamide, TIZ] is a new potent anti-infective agent which may enhance current therapies for leishmaniasis, Chagas disease and viral hepatitis. The aim of this study was to identify the conformational preferences that may be related to the biological activity of TIZ by resolving its crystal structure and characterizing various physicochemical properties, including its experimental vibrational and 13C nuclear magnetic resonance properties, behavior on heating and solubility in several solvents at 25 °C. TIZ crystallizes from dimethylformamide as the carboxamide tautomer in the triclinic system, space group P(−1) (No. 2) with the following unit cell parameters at 173(2) K: a = 5.4110(3) Å, b = 7.3315(6) Å, c = 13.5293(9) Å, α = 97.528(3), β = 95.390(4), γ = 97.316(5), V = 524.41(6) Å3, Z = 2, Dc = 1.680 g/cm3, R1 = 0.0482 and wR2 = 0.0911 for 2374 reflections. This modification of TIZ has a ‘graphitic’ structure and is composed of tightly packed layers of extensively hydrogen-bonded molecules. The various spectroscopic data [Diffuse Fourier transform infrared (DRIFT) and FT-Raman, recorded in the range 3600–500 and 4000–200 cm−1 respectively, and solid-state 13C NMR] were consistent with the structure determined by X-ray crystallography. From DSC, TG and thermomicroscopy, it was concluded that TIZ is thermally stable as a solid and that melting is not an isolated event from the one-step thermal decomposition that it undergoes above 270 °C. This modification of TIZ is practically insoluble in water and slightly soluble in polar aprotic solvents such as dimethylsulfoxide, dimethylformamide and dioxane.Fil: Bruno, Flavia Paola. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caira, Mino R.. University of Cape Town; SudáfricaFil: Ceballos Martin, Eliseo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monti, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Sperandeo, Norma Rebeca. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Determination of Azithromycin by an alternative FIA amperometric method for different pharmaceutical applications

This work presents a fast and reliable electroanalytical procedure for the quantification of azithromycin (AZ) in different systems that couples flow injection analysis and amperometric detection (FIA-AM). The quantification was performed at a working potential of 1.20 V (vs Ag/AgCl/NaCl (3 M)) in 0.05 M phosphate buffer at a flow rate of 1.0 mL min−1 . Under these conditions a 1.00 × 10−6 −1.50 × 10−5 M linear range, (5.8 ± 0.4) × 104 CAZ (μA M −1 ) sensitivity and 4.44 × 10−7 M limit of detection are obtained. Also, this technique can be used without sample pretreatment and presents good reproducibility. The procedure was applied to the determination of the content of AZ in commercial tablets, to study the intrinsic dissolution rate of compacts of AZ dihydrate, and to determine the AZ release from a AZ hydrogel and carbomer. The method was statistically analyzed and proves to be reliable and robust. However, more remarkable is that FIA-AM technique presents better sensitivity and high sampling rate.Fil: Pfaffen, Maria Valeria del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Faudone, Sonia Nerina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sperandeo, Norma Rebeca. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cuffini, Silvia Lucia. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba; Argentina. Universidade Federal Da Santa Catarina; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ortiz, Patricia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentin

Preparation and Characterization of Bosentan Monohydrate/ε‐Polycaprolactone Nanoparticles Obtained by Electrospraying

The electrospraying technique provides nano and microparticles that can be used as drug delivery systems. The aims of this study were, firstly, to optimize the influent parameters of electrospraying for the manufacture of a Bosentan (BOS) nanoparticulate platform, and secondly, to evaluate its physicochemical properties and in vitro biopharmaceutical behavior. Particles were characterized by scanning electron microscopy (SEM), powder X‐ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry (TG) and Fourier transformed Infrared spectroscopy (FTIR). Drug loading, encapsulation efficiency and kinetic dissolution were determined. Additionally, Bosentan release assays at 24 and 72 h were performed in vitro to evaluate biopharmaceutical properties of nano‐scaffolds by diffusion technique through dialysis bag. The nanostructures had heterogeneous sizes predominantly smaller than 550 nm and they were semicrystalline according to PXRD, indicating a partial amorphization of BOS during the encapsulation in the polymer matrix. FT‐IR and DSC showed an absence of chemical interactions between BOS and ε‐Polycaprolactone (PCL), suggesting that both components behaved as a physical mixture in these particles. The drug loading was 25.98%, and the encapsulation efficiency was 58.51%. Additionally, the release assays showed an extended and controlled release of BOS, in comparison to non‐encapsulated BOS. These data also showed to fit with the Cubic Root kinetic dissolution. As a conclusion, we demonstrate that the use of electrospraying for the manufacture of BOS (or similar drugs) controlled release nanoplatforms would represent an interesting contribution in the development of new therapeutic alternatives for the treatment of pathologies such as pulmonary hypertension and other related diseases.Fil: Martín Giménez, Virna Margarita. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; ArgentinaFil: Sperandeo, Norma Rebeca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Faudone, Sonia Nerina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Noriega, Sandra. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; ArgentinaFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Kassuha, Diego Enrique. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin