In vivo biodistribution of venlafaxine-PLGA nanoparticles for brain delivery: plain vs. functionalized nanoparticles.

Background: Actually, no drugs provide therapeutic benefit to approximately one-third of depressed patients. Depression is predicted to become the first global disease by 2030. So, new therapeutic interventions are imperative.Research design and methods: Venlafaxine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were surface functionalized with two ligands against transferrin receptor to enhance access to brain. An in vitro blood-brain barrier model using hCMEC/D3 cell line was developed to evaluate permeability. In vivo biodistribution studies were performed using C57/bl6 mice. Particles were administered intranasal and main organs were analyzed.Results: Particles were obtained as a lyophilized powder easily to re-suspend. Internalization and permeability studies showed the following cell association sequence: TfRp-NPs>Tf-NPs>plain NPs. Permeability studies also showed that encapsulated VLF was not affected by P-gP pump efflux increasing its concentration in the basolateral side after 24 h. In vivo studies showed that 25% of plain NPs reach the brain after 30 min of one intranasal administration while less than 5% of functionalized NPs get the target.Conclusions: Plain NPs showed the highest ability to reach the brain vs. functionalized NPs after 30 min by intranasal administration. We suggest plain NPs probably travel via direct nose-to-brian route whereas functionalized NPs reach the brain by receptor-mediated endocytosis.

Role of Nanotechnology for Enzyme Replacement Therapy in Lysosomal Diseases. A Focus on Gaucher's Disease.

Lysosomal storage diseases (LSDs) comprise a group of rare inherited chronic syndromes that cause deficiency of specific native enzymes within the lysosomes. The macromolecular compounds that are usually catabolized by lysosomal enzymes are accumulated within these organelles, causing progressive damage to tissues, skeleton and organs and, in several cases, the central nervous system (CNS). The damage caused by substrate accumulation finally results in physical deterioration, functional impairment and potential death. Up to date, the most promising therapy for most LSDs is enzyme-replacement therapy (ERT), which provides patients with the corresponding active enzyme. However, these enzymes do not have enough stability in blood, the treatment must be therefore periodically administrated by i.v. infusion under medical supervision, and immunogenicity issues are frequent. In addition, affected areas within the CNS, where the blood-brain barrier (BBB) is a major obstacle, cannot be reached by the enzymes. Nanotechnology can provide useful carriers to successfully protect and preserve enzymes, and transport them through the BBB towards brain locations. Several strategies based on targeting specific receptors on the BBB have led to nanoparticles that successfully carry sensitive molecules to the brain. Then, the main LSDs are described and a thorough review of nanotechnology strategies for brain delivery studied up to date is presented.

Lipid nanoparticles as an emerging platform for cannabinoid delivery: physicochemical optimization and biocompatibility.

This work aims at developing and optimizing a valuable oral delivery carrier for the cannabinoid derivative CB13, which presents a high therapeutic potential in chronic pain states that respond poorly to conventional analgesics, but also shows highly unfavorable physicochemical properties. CB13-loaded lipid nanoparticles (LNP) formulations were developed through solvent-emulsion evaporation and optimized in terms of physicochemical properties, long-term stability, integrity under gastric simulated conditions and in vitro interaction with NIH 3T3, HEK 293T and Caco-2 cells. An optimized formulation of LNP containing CB13 was obtained from a wide range of conditions assayed and analyzed. The selection of the lipid core, production conditions and the inclusion of lecithin proved to be key factors for the final properties of encapsulation, integrity and performance of the carriers. The LNP formulation proposed proved to be a promising carrier for the oral delivery of CB13, a cannabinoid with high therapeutic potential in chronic pain states that currently lack a valid oral treatment.

In vitro and in vivo evaluation of Δ9-tetrahidrocannabinol/PLGA nanoparticles for cancer chemotherapy.

Nanoplatforms can optimize the efficacy and safety of chemotherapy, and thus cancer therapy. However, new approaches are encouraged in developing new nanomedicines against malignant cells. In this work, a reproducible methodology is described to prepare Δ(9)-tetrahidrocannabinol (Δ(9)-THC)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles against lung cancer. The nanoformulation is further improved by surface functionalization with the biodegradable polymers chitosan and poly(ethylene glycol) (PEG) in order to optimize the biological fate and antitumor effect. Mean nanoparticle size (≈ 290 nm) increased upon coating with PEG, CS, and PEG-CS up to ≈ 590 nm, ≈ 745 nm, and ≈ 790 nm, respectively. Surface electrical charge was controlled by the type of polymeric coating onto the PLGA particles. Drug entrapment efficiencies (≈ 95%) were not affected by any of the polymeric coatings. On the opposite, the characteristic sustained (biphasic) Δ(9)-THC release from the particles can be accelerated or slowed down when using PEG or chitosan, respectively. Blood compatibility studies demonstrated the adequate in vivo safety margin of all of the PLGA-based nanoformulations, while protein adsorption investigations postulated the protective role of PEGylation against opsonization and plasma clearance. Cell viability studies comparing the activity of the nanoformulations against human A-549 and murine LL2 lung adenocarcinoma cells, and human embryo lung fibroblastic MRC-5 cells revealed a statistically significant selective cytotoxic effect toward the lung cancer cell lines. In addition, cytotoxicity assays in A-549 cells demonstrated the more intense anticancer activity of Δ(9)-THC-loaded PEGylated PLGA nanoparticles. These promising results were confirmed by in vivo studies in LL2 lung tumor-bearing immunocompetent C57BL/6 mice.

Functional PLGA NPs for oral drug delivery: recent strategies and developments.

This article presents the potential of PLGA nanoparticles for the oral administration of drugs. Different strategies are used to improve oral absorption of these nanoparticles. These strategies are based on modification of nanoparticle surface properties. They can be achieved either by coating the nanoparticle surface with stabilizing hydrophilic bioadhesive polymers or surfactants, or by incorporating biodegradable copolymers containing a hydrophilic moiety. Some substances such as chitosan, vitamin E, methacrylates, lectins, lecithins, bile salts and RGD molecules are employed for this purpose. Of especial interest are nanoparticles production methods and, in order to improve oral bioavailability, the mechanism of each additive.

Development and validation of an RP-HPLC method for CB13 evaluation in several PLGA nanoparticle systems.

A simple, fast, and reversed-phase high-performance liquid chromatographic (RP-HPLC) method has been developed and validated for determining of a cannabinoid derivate, which displays potent antihyperalgesic activity, 1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone (CB13) into PLGA nanoparticles. Separation was achieved in a C18 column using a mobile phase consisting of two solvents: solvent A, consisting of acetonitrile : water : acetic acid (75 : 23.7 : 1.3 v/v), and solvent B, consisting of acetonitrile. An isocratic method (70 : 30 v/v), with a flow rate of 1.000 mL/min, and a diode array detector were used. The developed method was precise, accurate, and linear over the concentration range of analysis with a limit of detection and a limit of quantification of 0.5 and 1.25 µg/mL, respectively. The developed method was applied to the analysis of CB13 in nanoparticles samples obtained by three different procedures (SEV, FF, and NPP) in terms of encapsulation efficiency and drug release. Nanoparticles size and size distribution were also evaluated founding that NPP method presented the most lowest particle sizes with narrow-size distribution (≈320 nm) and slightly negative zeta potential (≈-25 mV) which presumes a suitable procedure for the synthesis of PLGA-CB13 nanoparticles for oral administration.

Drug targeting to cancer by nanoparticles surface functionalized with special biomolecules.

Nanoparticulate-based drug carriers have been developed to overcome the problems of conventional anticancer pharmacotherapy, i.e., the little specificity and low accumulation of the drug into the tumor interstitium, and the extensive biodistribution leading to severe toxicity. Unfortunately, conventional nanoparticles have been demonstrated to merely accumulate the loaded drug into organs associated to the reticuloendothelial system, e.g., the liver. Recently, drug delivery strategies involving the use of nanoplatforms surface decorated with unique biomolecules have demonstrated their potential in concentrating the chemotherapy agent specifically into the malignant cells. This review will be focused on the analysis of the current state of the art and future perspectives of such passive and active targeting strategies based on the enhanced permeability and retention effect and on a ligand-mediated transport, respectively. Special attention will be given to the use of these surface functionalized nanocarriers to overcome multi-drug resistances in cancer cells.

Nanostructures for drug delivery to the brain.

This review aims to summarize present approaches employed in delivering drugs to the central nervous system. Changes in blood-brain barrier (BBB) function have been reported in several neurological disorders. A brief description of the blood brain barrier and the main pathologies related to this barrier disfunction are described. Treatments for these disorders are based on several available strategies for delivering drugs into the brain, through circumvention of the BBB, as disruption of the BBB, prodrugs, molecular Trojan horses, among others. Particular attention will be placed on nanocarriers and more specifically on polymeric nanoparticles, which are presented as the most promising strategy for CNS delivery, helping drugs to be targeted more efficiently to the brain. This also allows attacking previously untreatable disorders such as brain tumors and other neurodegenerative diseases. New strategies and technologies commercialized by different pharmaceutical companies are also included.

Insulin-loaded PLGA microparticles: flow focusing versus double emulsion/solvent evaporation.

CONTEXT: Oral administration of insulin is severely limited by very low bioavailability. Biocompatible polymeric nanocarriers have been investigated to overcome this problem. Flow focusing (FF) has revolutionized current engineering of poly(D,L-lactide-co-glycolide) (PLGA) based micromedicines. This technique has never been used to formulate insulin-loaded PLGA microparticles. OBJECTIVE: Investigation of the benefits rising from the synthesis of insulin-loaded PLGA microplatforms by FF, compared to double emulsion/solvent evaporation method. MATERIALS AND METHODS: Both synthesis methodologies were compared in terms of geometry, surface physicochemical properties and insulin vehiculization capabilities. The stability of the peptide during the formulation procedure was further analysed. RESULTS: FF permitted the preparation of insulin-loaded microcarriers with better geometry and physicochemical properties for the oral route, along with greater insulin loading capabilities and sustained insulin release kinetics. DISCUSSION AND CONCLUSION: Results have lead to the identification of the best formulation conditions for the engineering of insulin-loaded PLGA microparticles against diabetes.

Possibilities of poly(D,L-lactide-co-glycolide) in the formulation of nanomedicines against cancer.

Due to a very poor specificity, many chemotherapy agents generate a low antitumor effect and important severe side effects. Poly(D,L-lactide-co-glycolide) (PLGA)-based nanomedicines are under investigation to assure a very efficient anticancer activity in chemotherapy. In this work, we analyze the major applications of this FDA-approved biodegradable polymer in the formulation of nanomedicines against cancer. Despite conventional PLGA colloids could be only used to target tumors located into the mononuclear phagocyte system (MPS), special strategies are under intensive research to enhance the accumulation of anticancer drugs into any given tumor site. These are passive targeting (through the enhanced permeability and retention effect, so-called EPR effect), drug delivery through stimuli-sensitive colloids, and ligand-mediated targeting. We further discuss unique approaches of PLGA colloids in oral chemotherapy, drug delivery to brain tumors, and multi-drug resistance of cancer cells.

Valoración de la aplicación de un proyecto de innovación docente en la asignatura de Tecnología Farmacéutica de la Facultad de Farmacia de la Universidad de Sevilla / Evaluation of the implementation of a teaching innovation project in the subject of Pharmaceutical Technology, Faculty of Pharmacy, University of Seville

Se pretende determinar cómo se van resolviendo algunos problemas observados en el alumnado (ciertaapatía y falta de desarrollo de algunas habilidades) al tiempo que estudiar el impacto que esto supone en elrendimiento académico, gracias a una metodología que complementa a la tradicional en TecnologíaFarmacéutica. La mejora lograda ha sido muy esperanzadora. El seguimiento realizado ha detectado eldesarrollo de determinadas habilidades académicas, personales y profesionales por parte del alumnado. Sehan valorado cualitativamente otros aspectos que impulsan al alumno hacia un estudio activo de estaasignatura(AU)

In order to improve some skills and attitudes in the students of the subject of Pharmaceutical Technology,an innovation in the teaching methodologies have been assayed. The idea of the present study is todetermine the influence of this new strategy. It has been found an important amelioration in several aspectsrelated to academicals parameters. Moreover, it have been detected some improvements related to severalacademicals, personal and professional skills. Other aspects that drive students to an active study of thissubject has been assessed in a qualitative manner(AU)

Programa de Alumnos Tutores de la Facultad de Farmacia de la US (2006/07 - actualidad): análisis DAFO efectuado por los Alumnos Tutores / Student Mentoring Program at the Faculty of Pharmacy, University of Seville (2006/07 - present): SWOT analysis carried out by Mentor Students

ininterrumpidamente desde 2006/07 hasta la actualidad. Propósito: tutela de alumnos de nuevo ingreso por parte de alumnos de cursos superiores (AATT) bajo la supervisión de Profesores Tutores. Pretende generar una actitud responsable en los AATT y favorecerles el desarrollo de habilidades sociales. El objetivo de este trabajo es recoger las opiniones de los AATT (algunos comenzaron en ediciones anteriores y continúan desinteresadamente). Se aborda mediante un análisis DAFO. Conclusión: se han detectado factores estratégicos críticos, para una vez identificados, usarlos y apoyar en ellos la marcha del “Programa de Alumnos Tutores”, consolidando las fortalezas, minimizando las debilidades, aprovechando las ventajas de las oportunidades, y eliminando o reduciendo las amenazas(AU)

The "Student Mentor Program" (Faculty of Pharmacy, US) has been running since 2006/07 – to present. Purpose: to mentor new students by senior students (Mentor Students) under the supervision of mentor professors. It aims to generate a responsible attitude in students and tutors to encourage the development of social skills. Objective: To collect the views of mentor students (some started in previous years and continue to selflessly), through a SWOT analysis. Conclusion: it has been found critical strategic factors. It intends to use these factors for strengthening the "Student Mentor Program"(AU)

Facultad de Farmacia de la Universidad de Sevilla: 4 Años de plan piloto para la adaptación al EEES. Actividades docentes realizadas para una mejora en la calidad de enseñanza y su repercusión en el alumnado / Faculty of Pharmacy of the University of Seville: 4 years of pilot plan - EHEA. Teaching activities for a better quality in the education and students repercussion

Debido a la entrada en vigor del nuevo modelo de aprendizaje propio del EEES, la Facultad de Farmaciade la US vio necesaria la adaptación del sistema actual a estos nuevos paradigmas, participando en un PlanPiloto que facilitara tanto a Profesores como a Alumnos y a PAS este proceso de cambio. Después deestudiar los datos estadísticos recopilados por los becarios designados por la Universidad de Sevilla paraapoyo a este proceso, así como del análisis de las distintas actividades recogidas en las guías docentes decada asignatura, se comprobó que la realización de estas actividades beneficiaba positivamente la calidadde la enseñanza. Se hizo patente el aumento del dinamismo en las clases, viéndose mejorada con laparticipación del alumnado. Como resultado se obtuvo un aumento de asistencia a los exámenes y unmayor índice de aprobados. Con ello, se ha comprobado cómo este sistema ayuda a fomentar unaprendizaje de calidad, y lo que es más importante, proporciona al alumno las cualidades necesarias yespecíficas que demanda el mundo laboral, propias de competencias transversales, como son liderazgo,iniciativa, trabajo en grupo, conocimiento de nuevas tecnologías, así como conocimientos generales yespecíficos de nuestra rama. Con los datos procesados, se puede evaluar la mejora en la calidad de laenseñanza, y poner de manifiesto la efectividad de la experiencia(AU)

Before entering into the Degree of Pharmacy (EHEA), the Faculty of Pharmacy of the University ofSeville has worked in a Pilot Plan for the implementation of the EHEA. This has helped teachers andstudents to the process of adaptation. The analysis of (i) statistical data and (ii) innovation teachingactivities developed in the several subjects have pointed out the positive impact of this Pilot Plan over thequality of the teaching procedures. More dynamic classes, more assistance to the exams and moresuccessful results have been produced. The Pilot Plan have helped to achieve a more quality learning.Moreover, this experience have allowed to develop several generic skills of great interest for our students.The processed data obtained during this 4 years has allowed us to evaluate the impact of Pilot Plan for theimplementation of the ECTS system, as well as to highlight the effectiveness of the process. It have beenidentified improvement points before the full incorporation of our Faculty of Pharmacy into the EHEA(AU)

Impacto del Plan Piloto para el EEES en la Facultad de Farmacia de la Universidad de Sevilla / Impact of the Pilot Plan for the EHEA in the Faculty of Pharmacy, University of Seville

La Facultad de Farmacia de la US ha comenzado (2009/10) los estudios de “Grado en Farmacia” (1º curso), que irá sustituyendo gradualmente al actual Plan de Estudios de la Licenciatura. Previo a ello, nuestra Facultad ha participado en un Plan Piloto de adaptación al EEES (4 años) que ha supuesto un efectivo entrenamiento para el Profesorado, Alumnado y PAS, en todo lo relativo al EEES. El éxito de esta acción se ha debido a la estrecha colaboración entre la Facultad, considerando tanto todos sus Departamentos como la Dirección del Centro, y el Rectorado de la US. Con objeto de facilitar estas tareas, contamos con la ayuda de Becarios para el Plan Piloto (1/curso). Funciones: colaborar en las iniciativas propuestas por los Profesores Coordinadores de las asignaturas implicadas (1º-4º) relacionadas con el EEES. Entre otras, elaborar y analizar encuestas para recabar información (alumnado y profesorado) sobre el seguimiento del Plan Piloto (visión más completa de la acción). Esta información se traduce en gráficas explicativas que reflejan la evolución del proyecto. Hoy disponemos de material para evaluar la progresión de esta iniciativa. Esto ha facilitado la detección de necesidades previas a la implantación de los nuevos planes de estudio según ECTS.Resultados muy positivos: no sólo ha aumentado el número de actividades destinadas a facilitar el aprendizaje, sino la motivación y mejora en los resultados académicos. El procesamiento de los datos permite hacer una evaluación aproximada de la mejora que ha supuesto la acción, poniendo de manifiesto la efectividad de la experiencia(AU)

The Faculty of Pharmacy of the University of Seville has started (2009/10) the studies of the "Degree in Pharmacy” (EHEA) (1st year), which will gradually replace the actual Plan of Studies. Prior to that, our Faculty has participated in a Pilot Plan for adaptation to the EHEA, which has provided an effective training for teachers, students and PAS, in all matters relating to the EHEA. The success of this action was due to close collaboration between the Faculty, considering all their Departments and its Deanship, and the Government Team of the University of Seville. To facilitate these tasks, we have the help of Scholarship for the Pilot Plan (1/course). Duties: to assist in the initiatives proposed by Professors Coordinators of the subjects, related to the EHEA. Among others, to develop and to analyze surveys to gather information (students and teachers) on the Monitoring of the Pilot. This information is translated into explanatory graphs showing the development of the project. Now, we have material to assess the progression of thisinitiative. This has facilitated the detection of needs prior to introducing the new Degree according to ECTS.Results are positive: the number of activities to facilitate learning as well as the motivation has been increased; furthermore, it has been improved academic outcomes. The processing of data allows a rough assessment of the improvement that has brought the action, highlighting the effectiveness of the experience(AU)

Acción tutorial en el EEES en la Facultad de Farmacia de la us: 4 años de experiencia de un programa de alumnos tutores / Tutorial action in the EHEA at the Faculty of Pharmacy of us: 4 years of experience of a student mentoring program

La Facultad de Farmacia de la Universidad de Sevilla (US) tiene en marcha un Programa de Alumnos Tutores desde 2006/07 con el objetivo de que alumnos de cursos superiores (AATT) tutelen a alumnos de nuevo ingreso (1x3). Pretende generar una actitud responsable en los AATT y favorecerles el desarrollo de habilidades sociales, objetivos cualitativos dentro de la educación universitaria que sirven como preparación previa a su inserción en el mundo laboral. La actividad es supervisada por Profesores Tutores (1x3) que analizan la evolución de ambos grupos de alumnos. Es una supervisión activa a través de distintas vías de acción para ayudar a la consecución de objetivos, tales como entrevistas periódicas, revisión de informes, acciones de apoyo como charlas sobre técnicas de estudio, coloquios sobre salidas laborales, exposiciones de las experiencias personales de algunos alumnos recientemente egresados, gestión estratégica de búsqueda de empleo, elaboración de portafolios,…Con respecto a la evolución del programa, el número de profesores ha crecido moderadamente llegando a una situación estable, mientras que el número de alumnos, tanto tutores como tutelados, ha crecido en un ritmo constante acorde a las restricciones indicadas. Los resultados son muy positivos, entendiéndose que el proyecto se enmarca en un contexto más cualitativo que cuantitativo y que el principal objetivo es el robustecimiento de la experiencia y asentar una dinámica de apoyo hacia los alumnos de nuevo ingreso y de planificación de tareas, tutela y responsabilidad en general de los alumnos tutores(AU)

The Faculty of Pharmacy of the University of Seville (US) has developed a Student Mentoring Program (from 2006/07 - present). The main objective of this project is that senior students act as Mentor Students for students at their first year in the University (1x3). It aims to generate a responsible attitude in mentor students and to promote the development of social skills, qualitative goals within higher education that serve as preparation prior to their integration into the world of work.This activity is supervised by Mentor Professors (1x3) that analyze the evolution of both groups of students. It is an active monitoring through various actions such as regular interviews, review of reports, support operations such as lectures on study skills, seminars on job opportunities, statements of personal experiences of some recently graduated students, strategic management job search, portfolio development...With regard to the development of the program, the number of Mentor Professors has grown moderately, reaching a stable condition, while the number of students, both tutor and supervised, has grown steadily in line with the restrictions indicated. The results are very positive, considering the more qualitative than quantitative character of the project and that the main objectives are the strengthening of the experience and the establishment of a dynamic support to the new students and scheduling and general responsibility for mentor students(AU)

Protein-loaded PLGA microparticles engineered by flow focusing: physicochemical characterization and protein detection by reversed-phase HPLC.

In the present study, a novel synthesis technique based on the flow focusing (FF) technology is investigated for the preparation of green fluorescent protein (GFP)-loaded poly(D,L-lactide-co-glycolide) (PLGA) microparticles. To our knowledge, this novel technique has never been applied to the formulation of proteins in polymeric systems. A simple, specific and rapid reversed-phase HPLC (RP-HPLC) method was validated for the determination of GFP in PLGA microparticles with the best chromatographic peak resolution, reduced run time and low cost of analysis. In order to achieve the finest GFP-loaded polymeric particles, experimental parameters mainly associated to the FF device were studied (liquid flow rate and pressure of the focusing air). Very high GFP encapsulation values (>90%) were obtained by this technique, and the electrokinetic characterization of these systems suggested that this protein was incorporated into the polymeric matrix. This study is intended to offer information on which to base the development of high molecular weight protein-loaded polymeric delivery systems prepared by FF.

Consenso español sobre la preparación de mezclas nutrientes parenterales 2008 / No disponible

No disponible

Development and in vitro evaluation of a controlled release formulation to produce wide dose interval morphine tablets.

In this paper, a new pharmaceutical formulation for the administration of morphine has been developed. This system is based on a polymeric complex previously characterized. After the studies performed, it has been selected the following formulation: 62.5% of morphine complex, 15% of free morphine and 22.5% of Eudragit RS. The morphine formulation proposed has been characterized by means of the study of the influence of several parameters such as pH, ionic strength, mean particle diameter of the components and total morphine dose by means of the tablet dimensions. This assayed formulation is able to provide a specific in vitro release profile that will be no influenced by possible variations in the GIT conditions. Moreover, this formulation can reproduce the same biopharmaceutical behaviour in an independent manner of the mean diameter particle of the components and the dimension of the tablet produced with several doses inside a wide interval of doses.

Synthesis of lidocaine-loaded PLGA microparticles by flow focusing. Effects on drug loading and release properties.

In the present work, two methods for the preparation of lidocaine-loaded PLGA microparticles are compared. The differences between the polymeric particles obtained by solvent evaporation (SEVM) or flow focusing (FF) were studied by means of scanning electron microscopy and surface thermodynamics determinations. A detailed investigation of the capabilities of the polymer particles to load this drug is described. The physical state of the drug in the polymeric particles and the existence of interactions between both entities were studied by differential scanning calorimetry. The main factors determining the lidocaine incorporation and the release kinetics were the synthesis procedure followed, the amount of drug dissolved in the organic phase during the synthesis routine, the type of polymer (molecular weight and end chemical groups) and the size and the hydrophobic/hydrophilic properties of the particles. The FF technology allowed higher drug incorporations and slower release kinetics. The release studies showed a biphasic profile probably due to diffusion-cum-degradation mediated processes.

Elaboration and "in vitro" characterization of 5-ASA beads.

The purpose of this research was to perform the design and in vitro evaluation of alginate beads containing 5-ASA in order to achieve an oral system that protects the drug until it reaches the colon. Alginate beads were prepared by the well-known ionic gelation reaction (Ca2+). The influence of the incorporation of several polymers (Eudragit FS 30D, Eudragit S100, and chitosan) in the initial formulation was studied. In all formulations, entrapment efficiencies of the drug higher than 70% were obtained. The scanning electron microscopy (SEM) study of beads showed homogeneous sizes and shapes in all cases. Finally, the release behavior of these polymeric beads were also studied and compared. The results indicated that Eudragit FS 30D (26%) showed the most favorable dissolution behavior in terms of achieving a controlled release of 5-ASA. To determine the mechanism of drug release from these beads, the Korsmeyer equation was applied. Qt/Qinfinity <0.9 can be described using a Higuchi model and Qt/Qinfinity=0.7 showed a zero-order release period. This formulation was assayed at other different pH values (pH=6; 6.8; 7.2) to assure that there is no release of 5-ASA until the system reaches the colon. No release was observed at pH 6.0. Release was very slow at pH 6.8; averages about 20% an hour at pH 7.2 and was complete within 4 hour at pH 7.4. So, these Eudragit FS beads exhibited interesting dissolution profiles for the therapy of colon pathologies.