Hidrogeles poliiónoicos de chitosán y ácido poliacrílico como nuevos sistemas delibreación gástrica de amoxicilina para el tratamiento de "H. pylori"

Este trabajo experimental incluye la obtención de diferentes hidrogeles liofilizados compuestos por chitosán y ácido poliacrílico, unidos por enlaces no covalentes para la administración gástrica de amoxicilina en el tratamiento de H.pylori. Se ha estudiado la influencia de varias relaciones de ambos polímeros, la utilización de amoxicilina no ionizada o en forma de sal sódica, la fuerza iónica y el volumen del medio formador del hidrogel. Mediante técnicas como la microscopía electrónica de barrido, espectroscopoa de infrarrojos, cuantificación del principio activo por cromatografía de líquidos de alta resolución (HPLC), estudios de hinchamiento y estudios de cesión se caracterizaron los distintos hidrogeles. Se seleccionaron dos formulaciones para el estudio in vivo de su vaciamiento gástrico por medio de la prueba del aliento con ácido octanoico marcado con [13C] en voluntarios sanos. Asimismo se realizó un estudio comparativo de la estabilidad de la amoxicilina en medio simulado gástrico en tres tipos de formulaciones galénicas distintas: en solución, cápsulas convencionales y en hidrogel mediante PHLC. Por último se realizaron estudios in vivo de la influencia de la administración de dos fármacos (omeprazol y almagato), que elevan el pH intragástrico en el tránsito gástrico de un hidrogel seleccionado en voluntarios sanos. Estos estudios han permitido seleccionar un hidrogel de chitosán y ácido poliacrílico que podía utilizarse en combinación con la terapia erradicadora convencional de H.pylor

Creación de nuevo recurso educativo virtual para estudiantes de grado en Farmacia

Depto. de Farmacia Galénica y Tecnología AlimentariaFac. de FarmaciaFALSEsubmitte

Creación de un nuevo recurso educativo virtual para estudiantes de grado en Farmacia

Creación de un nuevo recurso educativo virtual para estudiantes de grado en Farmacia sobre la serialización de los medicamentos y los procesos de mezclado

Enhancement of the Dissolution Rate of Indomethacin by Solid Dispersions in Low-substituted Hydroxypropyl Cellulose

En el presente estudio, se desarrollaron nuevas formulaciones de indometacina para mejorar la velocidad de disolución de la indometacina mediante la preparación de dispersiones sólidas mediante el método de liofilización. El grado de alteración de la cristalinidad de la indometacina se evaluó según el método de preparación y mediante la adición de hidroxipropilcelulosa poco sustituida. Las dispersiones sólidas mejoraron la velocidad de disolución de la indometacina. El uso combinado de microscopía electrónica de barrido, difracción de rayos X en polvo y calorimetría diferencial de barrido reveló la base del aumento en la velocidad de disolución de la indometacina cuando se formula como dispersiones sólidas de hidroxipropilcelulosa poco sustituidas.In the present study, new indomethacin formulations were developed in order to enhance the indomethacin dissolution rate by preparing solid dispersions using the freeze-drying method. The degree of alterations in the crystallinity of indomethacin was assessed according to the preparation method and by the addition of low-substituted hydroxypropyl cellulose. Solid dispersions improved the dissolution rate of indomethacin. Combined use of scanning electron microscopy, X-ray powder diffraction and differential scanning calorimetry revealed the basis of the increase in dissolution rate of indomethacin when formulated as lowsubstituted hydroxypropyl cellulose solid dispersions.Department of Biomedical Sciences, Alcalá University, SpainDepartment of Physical Chemistry, Faculty of Chemical Sciences, Madrid Complutense University, SpainDepto. de Farmacia Galénica y Tecnología AlimentariaFac. de FarmaciaTRUEpu

Multiparticulate Systems of Meloxicam for Colonic Administration in Cancer or Autoimmune Diseases

The aim of this research is the development of new colonic release systems of meloxicam (MLX) a non-steroidal anti-inflammatory drug (NSAIDs) with pH and time-dependent vehicles for cancer or autoimmune diseases. The colon has a higher pH than the rest of the gastrointestinal tract (GIT) and this can be used as a modified release strategy. Eudragit® polymers are the most widely used synthetic products in the design of colonic release formulations because they might offer mucoadhesiveness and pH-dependent release. Colonic delivery systems produced with pH-dependent and permeable polymers (FS-30D) or with pH-independent and low permeability polymers (NM-30D), must dissolve at a pH range of 6.0–7.0 to delay the release of the drug and prevent degradation in the GIT, before reaching the colon. The conditions prepared to simulate a gastrointestinal transit showed the CNM multiparticulate system, composed of Eudragit® NM and cellulose, as the best release option for MLX with a more sustained release with respect to the other formulations. CNM formulation followed Higuchi and First-order release kinetics, thus MLX release was controlled by a combination of diffusion and polymers swelling/eroding processes

Multiparticulate Systems of Meloxicam for Colonic Administration in Cancer or Autoimmune Diseases

The aim of this research is the development of new colonic release systems of meloxicam (MLX) a non-steroidal anti-inflammatory drug (NSAIDs) with pH and time-dependent vehicles for cancer or autoimmune diseases. The colon has a higher pH than the rest of the gastrointestinal tract (GIT) and this can be used as a modified release strategy. Eudragit® polymers are the most widely used synthetic products in the design of colonic release formulations because they might offer mucoadhesiveness and pH-dependent release. Colonic delivery systems produced with pH-dependent and permeable polymers (FS-30D) or with pH-independent and low permeability polymers (NM-30D), must dissolve at a pH range of 6.0–7.0 to delay the release of the drug and prevent degradation in the GIT, before reaching the colon. The conditions prepared to simulate a gastrointestinal transit showed the CNM multiparticulate system, composed of Eudragit® NM and cellulose, as the best release option for MLX with a more sustained release with respect to the other formulations. CNM formulation followed Higuchi and First-order release kinetics, thus MLX release was controlled by a combination of diffusion and polymers swelling/eroding processes.Ministerio de Ciencia e Innovación, España.Universidad Complutense de MadridDepto. de Farmacia Galénica y Tecnología AlimentariaFac. de FarmaciaTRUEpu

Solid dispersions of atorvastatin with Kolliphor RH40: Enhanced supersaturation and improvement in a hyperlipidemic rat model

Atorvastatin is a potent lipid-lowering drug with poor solubility and high presystemic clearance that limits its therapeutic efficacy. The aim of this study was to develop solid dispersions and micellar systems to obtain fast -dissolving atorvastatin systems that enhances their anti-hyperlipidemic effect. Solubility and wettability studies allow the development of solid dispersions with low proportions of croscarmellose sodium as hydrophilic carrier. Solid state characterization studies indicated that the addition of Kolliphor (R) RH40 surfactant to solid dispersions increases intermolecular hydrogen bonding between drug and polymer chains. Dissolution studies in biorelevant Fasted State Simulate Intestinal Fluid (FaSSIF pH 6.5) medium showed for atorvastatin solid dispersion a su-persaturation peak of atorvastatin followed by an aggregation/precipitation process. Only the presence of a surfactant such as Kolliphor (R) RH40 in atorvastatin micellar system, promotes the presence of micelles that achieve delayed recrystallization. Efficacy studies were carried out using a hyperlipidemic model of rats fed with a high-fat diet. The atorvastatin micellar system at doses of 10 mg/kg, revealed a significant improvement in serum levels of total cholesterol, low-density lipoproteins, and triglycerides compared to atorvastatin raw ma-terial. This micellar system also exhibited more beneficial effects on liver steatosis, inflammation and ballooning injury.Universidad Complutense de MadridMinisterio de Ciencia e Innovación de España.Depto. de Farmacia Galénica y Tecnología AlimentariaFac. de FarmaciaTRUEpu

Enhanced bioavailability and anthelmintic efficacy of mebendazole in redispersible microparticles with low-substituted hydroxypropylcellulose

Antecedentes: el mebendazol (MBZ) es un fármaco extremadamente insoluble y, por lo tanto, poco absorbido y los resultados clínicos variables pueden correlacionarse con las concentraciones sanguíneas. La necesidad de un tratamiento prolongado con dosis altas de este fármaco aumenta el riesgo de efectos adversos. Métodos: En el presente estudio preparamos micropartículas redispersables (RDM) que contienen MBZ, un fármaco oral poco soluble en agua, en diferentes proporciones de hidroxipropilcelulosa poco sustituida (L-HPC). Investigamos las estructuras de micropartículas que emergen espontáneamente tras la dispersión de un RDM en medio acuoso y dilucidamos su influencia en la disolución, y también en su biodisponibilidad oral y eficiencia terapéutica utilizando un modelo murino de infección con el parásito nematodo Trichinella espiralis. Resultados: Se obtuvieron porcentajes elevados de fármaco disuelto con RDM en proporciones 1:2,5 y 1:5 de MBZ:L-HPC. El análisis térmico mostró una amorfización de MBZ en el RDM por la ausencia de un pico de fusión claro de MBZ en las formulaciones. El rápido comportamiento de disolución podría deberse a la disminución de la cristalinidad del fármaco, el rápido tiempo de disolución de portadores como L-HPC, junto con su superior dispersabilidad y excelentes propiedades humectantes. RDM-1:2,5 y RDM-1:5 dieron como resultado un aumento de la concentración plasmática máxima y de los valores de área(s) bajo la curva (AUC)(0-infinito). Asimismo, después de la administración oral de RDM-1:2,5 y RDM-1:5, el AUC(0-infinito) fue 2,67 y 2,97 veces mayor, respectivamente, en comparación con el MBZ puro. La actividad terapéutica, evaluada en el ciclo de vida de Trichinella espiralis, mostró que RDM-1:5 fue el más eficaz para reducir el número de parásitos (4,56 veces) en comparación con el MBZ puro, en estado enquistado. Conclusión: El MBZ: L-HPC RDM podría ser una forma efectiva de mejorar la biodisponibilidad oral y la actividad terapéutica utilizando dosis bajas de MBZ (5 mg/kg), lo que implica un bajo grado de toxicidad para los humanos.Background: Mebendazole (MBZ) is an extremely insoluble and therefore poorly absorbed drug and the variable clinical results may correlate with blood concentrations. The necessity of a prolonged high dose treatment of this drug increases the risk of adverse effects. Methods: In the present study we prepared redispersible microparticles (RDM) containing MBZ, an oral, poorly water-soluble drug, in different proportions of low-substituted hydroxypropylcellulose (L-HPC). We investigated the microparticulate structures that emerge spontaneously upon dispersion of an RDM in aqueous medium and elucidated their influence on dissolution, and also on their oral bioavailability and therapeutic efficiency using a murine model of infection with the nematode parasite Trichinella spiralis. Results: Elevated percentages of dissolved drug were obtained with RDM at 1:2.5 and 1:5 ratios of MBZ: L-HPC. Thermal analysis showed an amorphization of MBZ in the RDM by the absence of a clear MBZ melting peak in formulations. The rapid dissolution behavior could be due to the decreased drug crystallinity, the fast dissolution time of carriers as L-HPC, together with its superior dispersibility and excellent wetting properties. RDM-1:2.5 and RDM-1:5 resulted in increased maximum plasma concentration and area(s) under the curve (AUC)0-∞ values. Likewise, after oral administration of the RDM-1:2.5 and RDM-1:5 the AUC0-∞ were 2.67- and 2.97-fold higher, respectively, compared to those of pure MBZ. Therapeutic activity, assessed on the Trichinella spiralis life cycle, showed that RDM-1:5 was the most effective in reducing the number of parasites (4.56-fold) as compared to pure MBZ, on the encysted stage. Conclusion: The MBZ: L-HPC RDM might be an effective way of improving oral bioavailability and therapeutic activity using low doses of MBZ (5 mg/kg), which implies a low degree of toxicity for humans.Universidad Complutense de MadridDepto. de Farmacia Galénica y Tecnología AlimentariaFac. de FarmaciaTRUEpu

Development of Chitosan/Sodium Carboxymethylcellulose Complexes to Improve the Simvastatin Release Rate: Polymer/Polymer and Drug/Polymer Interactions’ Effects on Kinetic Models

Simvastatin (SIM) is a potent lipid-lowering drug used to control hyper-cholesterolemia and prevent cardiovascular diseases. SIM presents low oral bioavailability (5%) because of its low aqueous solubility. In this work, polyelectrolyte complexes (PEC) are developed with different chitosan (CS) and carboxymethylcellulose (CMC) ratios that will allow for an increase in the SIM dissolution rate (2.54-fold) in simulated intestinal medium (pH 4.5). Scanning Electron Microscopy (SEM) images revealed highly porous structures. The changes between both complexes, PEC-SIM:CS:CMC (1:1:2) and (1:2:1), were related to the relaxation of the polymer chains upon absorption of the dissolution medium. Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (XRPD) studies were used to evaluate the polymer/polymer and drug/polymer interactions on the different PEC-SIM:CS:CMC ratios. In addition, the PEC-SIM:CS:CMC (1:2:1) complex exhibited a high ratio of protonated amino groups (NH3+) and an increase in intramolecular hydrogen bonds, which were correlated with a high expansion of the interpolymer chains and an increase in the SIM dissolution rate. Different kinetic models such as zero-order, first-order, Higuchi and Korsmeyer–Peppas were studied to evaluate the influence of CS/CMC ionic interactions on the ability to improve the release rate of poorly soluble drugs.Ministerio de Ciencia e Innovación, España.Universidad Complutense de MadridDepto. de Farmacia Galénica y Tecnología AlimentariaFac. de FarmaciaTRUEpu

Topical Meloxicam Hydroxypropyl Guar Hydrogels Based on Low-Substituted Hydroxypropyl Cellulose Solid Dispersions

Meloxicam (MX) is a poorly water-soluble drug with severe gastrointestinal side effects. Topical hydrogel of hydroxypropyl guar (HPG) was formulated using a solid dispersion (SD) of MX with hydroxypropyl cellulose (LHPC) as an alternative to oral administration. The development of a solid dispersion with an adequate MX:LHPC ratio could increase the topical delivery of meloxicam. Solid dispersions showed high MX solubility values and were related to an increase in hydrophilicity. The drug/polymer and polymer/polymer interactions of solid dispersions within the HPG hydrogels were evaluated by SEM, DSC, FTIR, and viscosity studies. A porous structure was observed in the solid dispersion hydrogel MX:LHPC (1:2.5) and its higher viscosity was related to a high increase in hydrogen bonds among the –OH groups from LHPC and HPG with water molecules. In vitro drug release studies showed increases of 3.20 and 3.97-fold for hydrogels with MX:LHPC ratios of (1:1) and (1:2.5), respectively, at 2 h compared to hydrogel with pure MX. Finally, a fitting transition from zero to first-order model was observed for these hydrogels containing solid dispersions, while the n value of Korsmeyer–Peppas model indicated that release mechanism is governed by diffusion through an important relaxation of the polymer.Ministerio de Ciencia e InnovaciónUniversidad Complutense de MadridDepto. de Farmacia Galénica y Tecnología AlimentariaFac. de FarmaciaInstituto Universitario de Farmacia IndustrialTRUEpubDescuento UC