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1.
Expert Opin Drug Deliv ; 16(12): 1413-1427, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31694417

RESUMO

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.


Assuntos
Antidepressivos , Portadores de Fármacos , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Cloridrato de Venlafaxina , Administração Intranasal , Animais , Antidepressivos/administração & dosagem , Antidepressivos/farmacocinética , Encéfalo/metabolismo , Linhagem Celular , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagem , Nanopartículas/química , Permeabilidade , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacocinética , Distribuição Tecidual , Cloridrato de Venlafaxina/administração & dosagem , Cloridrato de Venlafaxina/farmacocinética
2.
Curr Med Chem ; 23(9): 929-52, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26860997

RESUMO

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.


Assuntos
Terapia de Reposição de Enzimas , Terapia Enzimática , Doença de Gaucher/tratamento farmacológico , Nanomedicina/métodos , Enzimas/administração & dosagem , Humanos
3.
Int J Pharm ; 487(1-2): 205-12, 2015 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-25899283

RESUMO

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.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Dronabinol/administração & dosagem , Dronabinol/uso terapêutico , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Quitosana , Composição de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ácido Láctico , Teste de Materiais , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas , Tamanho da Partícula , Polietilenoglicóis , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Mini Rev Med Chem ; 13(1): 58-69, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22974367

RESUMO

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.


Assuntos
Portadores de Fármacos/química , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Administração Oral , Animais , Engenharia , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
5.
ScientificWorldJournal ; 2012: 737526, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22792051

RESUMO

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.


Assuntos
Analgésicos/isolamento & purificação , Cromatografia de Fase Reversa/normas , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Ácido Láctico/química , Nanopartículas/química , Naftalenos/isolamento & purificação , Ácido Poliglicólico/química , Administração Oral , Analgésicos/administração & dosagem , Analgésicos/química , Química Farmacêutica/métodos , Cromatografia de Fase Reversa/métodos , Portadores de Fármacos/administração & dosagem , Limite de Detecção , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Naftalenos/administração & dosagem , Naftalenos/química , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Reprodutibilidade dos Testes
6.
Curr Med Chem ; 19(19): 3188-95, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22612702

RESUMO

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.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Animais , Transporte Biológico , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Humanos , Nanomedicina/métodos
7.
Curr Med Chem ; 18(34): 5303-21, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22087827

RESUMO

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.


Assuntos
Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Sistema Nervoso Central/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Animais , Humanos
8.
J Microencapsul ; 28(5): 430-41, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21736527

RESUMO

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.


Assuntos
Portadores de Fármacos/química , Insulina/administração & dosagem , Ácido Láctico , Microesferas , Ácido Poliglicólico , Diabetes Mellitus/tratamento farmacológico , Emulsões , Humanos , Insulina/farmacocinética , Métodos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
9.
Curr Drug Targets ; 12(8): 1096-111, 2011 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21443478

RESUMO

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.


Assuntos
Antineoplásicos/uso terapêutico , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos , Excipientes/química , Ácido Láctico/química , Neoplasias/tratamento farmacológico , Ácido Poliglicólico/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Química Farmacêutica , Coloides/química , Vias de Administração de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Nanomedicina , Nanoestruturas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros
10.
Ars pharm ; 51(supl.2): 412-418, mayo 2010. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-88662

RESUMO

La implantación del EEES supone un importante reto para la docencia de numerosas universidades europeas y permite desarrollar iniciativas de innovación docente; esto es lo que en los últimos años se ha venido haciendo en diversas asignaturas de la Facultad de Farmacia de la Universidad de Sevilla. En este sentido, la asignatura de Gestión y Planificación, por su carácter eminentemente práctico, está especialmente indicada para implementar diversas actividades de innovación docente, entre ellas, el Aprendizaje Basado en Problemas (ABP). La estrategia docente consiste en el desarrollo en grupos reducidos de alumnos de un plan de marketing y/o merchandising en una oficina de farmacia concreta. Se pretende el desarrollo de cinco competencias genéricas: buscar información, trabajar en equipo, debatir en grupo y tomar decisiones, elaborar informes, y defender y debatir su trabajo en público.Desde la implantación generalizada de este tipo de actividad en el curso 2007/08 se comprueba una mayor implicación del alumno en la asignatura que se traduce en una mayor participación en el ABP, en el examen oficial, y en un mayor porcentaje de aprobados(AU)


The implementation of the EHEA is an important challenge for the teaching of many universities in Europe and enables the development of innovative teaching initiatives; this is what in recent years has been doing in different subjects of the Faculty of Pharmacy, University of Seville. In this sense, the subject of Management and Planning, by its practical nature, is suited to implement various activities of educational innovation, including Problem Based Learning (PBL). The teaching strategy is the development in small groups of students in a marketing plan and/or merchandising in a specific pharmacy. The aim is the development of five generic skills: searching for information, teamwork, group discussions and decisions, prepare reports, and defend and discuss their work in public.Since the widespread deployment of this type of activity during 2007/08 is found greater involvement of students in the subject that translates into greater participation in PBL, in the official examination, and a better pass rate(AU)


Assuntos
Humanos , Masculino , Feminino , 34002 , Políticas, Planejamento e Administração em Saúde/organização & administração , Políticas, Planejamento e Administração em Saúde/tendências , Docentes/organização & administração , Educação em Farmácia/organização & administração , Resolução de Problemas/ética , Aprendizagem Baseada em Problemas/métodos , Aprendizagem Baseada em Problemas/tendências , Farmácia/organização & administração , Organização e Administração/normas , Aprendizagem Baseada em Problemas/organização & administração , Aprendizagem Baseada em Problemas/normas , Inovação Organizacional , Política de Inovação e Desenvolvimento
11.
Ars pharm ; 51(supl.2): 487-493, mayo 2010. graf, ilus
Artigo em Espanhol | IBECS | ID: ibc-88672

RESUMO

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)


Assuntos
Humanos , Masculino , Feminino , Faculdades de Farmácia/organização & administração , Faculdades de Farmácia/tendências , Tutoria/métodos , Entrevista Psicológica/métodos , Mídia Audiovisual/normas , Mídia Audiovisual , Materiais de Ensino/normas , Faculdades de Farmácia/normas , Tutoria/organização & administração , Tutoria/normas , Tutoria/tendências , Comissão Para Atividades Profissionais e Hospitalares/normas
12.
Ars pharm ; 51(supl.2): 537-542, mayo 2010. graf
Artigo em Espanhol | IBECS | ID: ibc-88680

RESUMO

En este estudio se recogen datos sobre el conocimiento de los futuros profesionales respecto almercado laboral y a la formación de postgrado; se pretende obtener una herramienta docente paraorganizar estrategias que motiven y estimulen el proceso de enseñanza-aprendizaje. El diseño deinvestigación seleccionado fue de carácter descriptivo, con un cuestionario de 10 preguntas derespuestas múltiples agrupadas según proporcionan información sobre I) las necesidades deinformación laboral y búsqueda de empleo, II) los conocimientos sobre la formación de postgrado, yIII) el grado de conocimiento sobre los futuros desarrollos profesionales. Los alumnos reconocen quesus conocimientos sobre la gestión de una Oficina de Farmacia, Centro de Distribución o IndustriaFarmacéutica, eran escasos o nulos al iniciar la asignatura (70%); pero fueron considerados más quesuficientes para el 82% al final del curso. Igualmente, hasta un 85% de los alumnos aseguraron poseerpoca o ninguna información sobre aspectos de la gestión en Hospitales o Atención Primaria; pero alfinal de curso un 59% dicen poseer conocimientos suficientes en este campo(AU)


This study collects data on the knowledge of future professionals on the job market and graduatetraining. This can be useful for organizing strategies that motivate and stimulate the learning processof students. The selected research design was the descriptive type, such survey. We designed aquestionnaire of 10 multiple choice questions, grouped according provide information about the needsof I) labour market information and job search, II) knowledge of postgraduate training and III) theachievement of objectives of the activities related to information on relevant aspects of some futureprofessional developments. The students surveyed acknowledge that their knowledge on themanagement of a pharmacy, or Distribution Center, or Pharmaceutical Industry, were low or zerowhen starting the course (70%), but after the course, foreground were considered more than sufficientfor 82% of respondents. Similarly, up to 85% of students claimed to have little or no information on aspects of management in Hospital or Primary Care, end-of course 59% of students surveyed considered to possess more than enough expertise in this field(AU)


Assuntos
Humanos , Masculino , Feminino , Estudantes de Farmácia/estatística & dados numéricos , Educação em Farmácia , Educação em Farmácia/métodos , Educação em Farmácia/organização & administração , Sistemas de Informação , Farmacêuticos/organização & administração , Assistência Farmacêutica , Descrição de Cargo/normas , Administração Farmacêutica , Tecnologia Farmacêutica , Educação de Pós-Graduação em Farmácia , Educação de Pós-Graduação em Farmácia/organização & administração , Química Farmacêutica/organização & administração , Satisfação no Emprego , Indústria Farmacêutica/organização & administração
13.
Int J Pharm ; 380(1-2): 147-54, 2009 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-19635540

RESUMO

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.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Portadores de Fármacos , Composição de Medicamentos/instrumentação , Composição de Medicamentos/métodos , Proteínas de Fluorescência Verde/química , Ácido Láctico , Ácido Poliglicólico , Materiais Biocompatíveis/química , Fenômenos Químicos , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Ácido Láctico/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
14.
Eur J Pharm Biopharm ; 70(2): 544-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18588973

RESUMO

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.


Assuntos
Morfina/química , Química Farmacêutica , Preparações de Ação Retardada , Concentração de Íons de Hidrogênio , Morfina/administração & dosagem , Concentração Osmolar , Solubilidade , Comprimidos
15.
Int J Pharm ; 358(1-2): 27-35, 2008 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-18372128

RESUMO

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.


Assuntos
Anestésicos Locais/administração & dosagem , Anestésicos Locais/síntese química , Lidocaína/administração & dosagem , Lidocaína/síntese química , Algoritmos , Varredura Diferencial de Calorimetria , Química Farmacêutica , Composição de Medicamentos , Ácido Láctico , Microscopia Eletrônica de Varredura , Nanopartículas , Tamanho da Partícula , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Solubilidade , Termodinâmica
16.
Drug Dev Ind Pharm ; 31(2): 231-9, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15773290

RESUMO

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.


Assuntos
Alginatos/química , Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/química , Materiais Biocompatíveis/química , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Mesalamina/análise , Mesalamina/química , Administração Oral , Calibragem , Colo , Preparações de Ação Retardada , Portadores de Fármacos , Humanos , Microscopia Eletrônica de Varredura , Microesferas , Solubilidade
17.
J Drug Target ; 12(9-10): 607-12, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15621686

RESUMO

A new oral drug delivery system for colon targeting has been developed based on enteric-coated matrix tablets which suitably exploits both pH-sensitive and time-dependent functions. Matrix-tablets were prepared by direct compression of mixtures of hydroxyethylcellulose (HEC), a hydrophilic swellable polymer, with the inert insoluble ethylcellulose (EC) or micro-crystalline cellulose (MCC) polymers, in which theophylline, selected as model drug, was dispersed. Eudragit S100, a methacrylic acid copolymer soluble at pH 7, was used as pH-sensitive coating polymer. The influence of varying the cellulose-derivative combinations and their relative ratios as well as the level of the coating polymer was investigated. Surface morphology of the tablets was monitored by SEM analysis before and after the release test. The results of release studies, performed according to the USP basket method using a sequence of dissolution media simulating the gastrointestinal physiological pH variation, indicated that the Eudragit S100 enteric-coated matrix tablets were successful in achieving gastric resistance and timed-release of the drug, assuring an adequate lag time for the intended colonic targeting, followed by a controlled-release phase. The enteric-coating level emerged as the critical factor in determining the duration of the lag-phase, whereas the release rate mainly depended on the matrix composition. Formulations with higher HEC content showed a faster drug release rate than those with greater content in inert polymer and the MCC-HEC combinations were more effective than the corresponding EC-HEC ones. The best results were given by the 27% coated 1:0.3:0.7 (w/w) drug/MCC/HEC tablets, which, after a 260 min lag time, regularly released the drug, achieving about 90% of release after 10 h.


Assuntos
Colo/metabolismo , Preparações de Ação Retardada/síntese química , Sistemas de Liberação de Medicamentos/métodos , Comprimidos com Revestimento Entérico/síntese química , Química Farmacêutica , Preparações de Ação Retardada/farmacocinética , Comprimidos com Revestimento Entérico/farmacocinética
18.
Farmaco ; 57(8): 649-56, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12361232

RESUMO

Inert matrices of didanosine (ddI) were elaborated as controlled release dosage forms, using two different types of polymers: Eudragit RS-PM, an anionic acrylic acid copolymer, and Ethocel 100 Premium, an ethylcellulose. A preformulation study of the drug was designed to address the following points: (a) the development of two alternative methods (high performance liquid chromatography (HPLC) and UV spectrophotometry) for the analysis and quantifying of ddI; (b) the determination of the aqueous solubility of ddI; and (c) the characterization of ddI from the following points of view: morphological (scanning electronic microscopy (SEM)) and thermal (differential scanning calorimetry (DSC)). Furthermore, some of these techniques were used for the characterization of those components which will be included in the oral controlled release system to be developed. The in vitro release of ddI matrices was studied at pH 7.4, because of the instability of ddI at pH values lower than 3 units. A significant reduction in the release rate of drug from both ddI controlled release systems was found. Furthermore, Ethocel 100 Premium showed a minor efficiency in the dissolution process, with a reduction of more than double in the final dissolution efficiency (DE) value. This parameter and the fit factors (f1 and f2) have been compared for the characterization of dissolution profiles.


Assuntos
Resinas Acrílicas/química , Celulose/análogos & derivados , Celulose/química , Didanosina/química , Preparações de Ação Retardada/química , Solubilidade
19.
Cienc. tecnol. pharm ; 12(4): 173-179, oct. 2002. tab
Artigo em Es | IBECS | ID: ibc-19443

RESUMO

En el presente trabajo se resumen los pasos seguidos para optimizar un proceso de formación de complejos entre el Eudragit® L 30D y el clorhidrato de morfina con el fin de elaborar formas farmacéuticas de liberación controlada del citado fármaco y mejorar en lo posible, la calidad de vida de miles de pacientes aquejados de dolor severo crónico, pacientes a los que la morfina va dirigida. En esta primera parte se llevó a cabo un estudio sobre la posible influencia de la fuerza iónica sobre el rendimiento del proceso. Así mismo, se determinó la necesidad de emplear un exceso de fármaco respecto a la cantidad estequiométrica de grupos carboxílicos neutralizados del polímero en vista a optimizar la técnica de complejación (AU)


Assuntos
Morfina/química , Analgésicos Opioides/química , Morfina/administração & dosagem , Analgésicos Opioides/administração & dosagem , Concentração Osmolar , Cromatografia Líquida de Alta Pressão
20.
Cienc. tecnol. pharm ; 12(4): 190-201, oct. 2002. tab, ilus
Artigo em Es | IBECS | ID: ibc-19445

RESUMO

La posibilidad que ofrece el colon como lugar de absorción de fármacos, hace que en los últimos años esté aumentando el interés por conseguir una vía alternativa para aquellos principios activos, como los péptidos y las proteínas, que hasta ahora sólo podían ser administrados por la vía parenteral. En este artículo se intenta dar una visión general acerca de las características fisiológicas y anatómicas del colon así como una recopilación de las diferentes estrategias que se usan para conseguir la liberación y la absorción a nivel colónico (AU)


Assuntos
Humanos , Proteínas/farmacocinética , Proteínas/uso terapêutico , Colo/metabolismo , Proteínas/administração & dosagem , Colo/anatomia & histologia , Colo/fisiologia , Administração Oral
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