>Magister Scientiae - MSc / Liposomes as a drug carrier in the pharmaceutical industry has gained currency since its discovery in 1965 by Bangham A. D. Liposomes have been shown to improve bioavailability as they can be delivered to target sites and possess sustained release properties which could be used to mitigate certain weaknesses associated with current diclofenac sodium eye drops. Diclofenac sodium (DNa) eye drop is a sterile Nonsteroidal Anti-inflammatory Drug (NSAID) with diclofenac sodium as its active ingredient. It is indicated for the lessening of ocular pain, prevention of miosis in eye operations, easing of postoperative inflammation and cystoids macular edema. The residence time of eye drops after application has been found to be 1-2 minutes as a result of continuous production of tears diluting the active ingredient, draining the eye drops into the nasolacrimal path, and eliminating it during blinking. As a result of the active ingredient not residing at the target site for the required duration, more frequent administration and medication is required and the risk of non-compliance is increased. Given the aforementioned potential of liposomes to redress the above weaknesses of current eye drops (dosage form) available for diclofenac sodium ophthalmic application, this study sought to encapsulate diclofenac sodium into liposomes for ophthalmic application. The main components of liposomes (cholesterol and phosphotidylcholine) and incubation time were set as the independent variables while percentage encapsulation, polydispersity index (PDI) and drug release profile constituted the dependent variable. Using analysis of variance (ANOVA) and t-test statistics, the interaction between the independent variables and their effect on the dependent variables were tested.

Made available in DSpace on 2014-12-17T15:42:01Z (GMT). No. of bitstreams: 1 FranciscoFN_DISSERT.pdf: 2089554 bytes, checksum: 7f494e90c450d766696575e9a76682d2 (MD5) Previous issue date: 2012-02-29 / Universidade Federal do Rio Grande do Norte / This work is combined with the potential of the technique of near infrared spectroscopy - NIR and chemometrics order to determine the content of diclofenac tablets, without destruction of the sample, to which was used as the reference method, ultraviolet spectroscopy, which is one of the official methods. In the construction of multivariate calibration models has been studied several types of pre-processing of NIR spectral data, such as scatter correction, first derivative. The regression method used in the construction of calibration models is the PLS (partial least squares) using NIR spectroscopic data of a set of 90 tablets were divided into two sets (calibration and prediction). 54 were used in the calibration samples and the prediction was used 36, since the calibration method used was crossvalidation method (full cross-validation) that eliminates the need for a validation set. The evaluation of the models was done by observing the values of correlation coefficient R 2 and RMSEC mean square error (calibration error) and RMSEP (forecast error). As the forecast values estimated for the remaining 36 samples, which the results were consistent with the values obtained by UV spectroscopy / Neste trabalho s?o combinadas as potencialidades da t?cnica de espectroscopia no infravermelho pr?ximo NIR e da quimiometria visando ? determina??o do teor de diclofenaco em comprimidos, sem destrui??o da amostra, para o qual utilizou-se como refer?ncia o m?todo de espectroscopia no ultravioleta, que ? um dos m?todos oficiais. Na constru??o dos modelos de calibra??o multivariada estudou-se v?rios tipos de pr?processamento dos dados espectrais NIR, como corre??o do espalhamento da luz, primeira derivada. O m?todo de regress?o usado na constru??o dos modelos de calibra??o foi o PLS (m?nimos quadrados parciais) utilizando dados espectrosc?picos do NIR de um conjunto de 90 comprimidos divididos em dois conjuntos (calibra??o e previs?o). Na calibra??o foram usadas 54 amostras e na previs?o foram usadas 36, uma vez que o m?todo de calibra??o utilizada foi o m?todo de valida??o cruzada (full cross validation) que dispensa a necessidade de um conjunto de valida??o. A avalia??o dos modelos foi feita observando os valores de coeficiente de correla??o R2 e os erros quadrados m?dios RMSEC (erro de calibra??o) e RMSEP (erro de previs?o). Sendo os valores de previs?o estimados para as demais 36 amostras, o qual os resultados se mostraram coerentes com os valores obtidos por espectroscopia no ultravioleta

Submitted by Jean Medeiros (jeanletras@uepb.edu.br) on 2016-02-25T17:18:20Z No. of bitstreams: 2 license_rdf: 19874 bytes, checksum: 38cb62ef53e6f513db2fb7e337df6485 (MD5) PDF - Camilla Aquino Azevedo de Lucena.pdf: 2741876 bytes, checksum: a08dcc542ad13293807b17d3b9a600df (MD5) / Submitted by Jean Medeiros (jeanletras@uepb.edu.br) on 2016-03-09T12:34:51Z No. of bitstreams: 1 PDF - Camilla Aquino Azevedo de Lucena.pdf: 2741876 bytes, checksum: a08dcc542ad13293807b17d3b9a600df (MD5) / Approved for entry into archive by Secta BC (secta.csu.bc@uepb.edu.br) on 2016-03-09T12:38:12Z (GMT) No. of bitstreams: 1 PDF - Camilla Aquino Azevedo de Lucena.pdf: 2741876 bytes, checksum: a08dcc542ad13293807b17d3b9a600df (MD5) / Made available in DSpace on 2016-03-09T12:38:12Z (GMT). No. of bitstreams: 1 PDF - Camilla Aquino Azevedo de Lucena.pdf: 2741876 bytes, checksum: a08dcc542ad13293807b17d3b9a600df (MD5) Previous issue date: 2014-09-08 / Biodegradable films prepared from biopolymers such as polysaccharides, proteins, lipids or combinations of those components have received great interest in recent years. Xylan is the major hemicellulose in the plant kingdom and it accounts for onethird of renewable biomass available on earth. The aim of this work was to develop and characterize biodegradable films of xylan from corn cobs with potential use as transdermal formulations. Films were produced by casting the film-forming dispersions with different concentrations of xylan and glycerol. In addition, the gelatin was incorporated to xylan films. According to macroscopic characterization, three films were selected to evaluate the thickness, solubility, biodegradability, opacity, water content and microscopic morphology of the films. The best formulation was selected to study the incorporation of the drug (drug content and release profile). The results show that the macroscopic aspect of xylan/gelatin films was better than films containing only xylan, probably due the high solubility of the gelatin in the films. The increase in the polysaccharide concentration affected the films solubility, opacity, water content and thickness of films. The drug content was 87.88% and the drug release occurred mainly in the first 4h, followed by a slow release until the end of the study. / Filmes biodegradáveis desenvolvidos a partir de biopolímeros como polissacarídeos, proteínas, lipídeos ou através da combinação destes polímeros tem recebido grande interesse nos últimos anos. A xilana é a principal hemicelulose presente no reino vegetal e é responsável por um terço da biomassa renovável disponível na terra. O objetivo deste trabalho foi desenvolver e caracterizar filmes biodegradáveis à base xilana de sabugo de milho com potencial uso em formulações transdérmicas. Os filmes foram produzidos através da secagem das dispersões filmogênicas com diferentes concentrações de xilana e glicerol. Adicionalmente, a gelatina foi incorporada aos filmes. De acordo com a caracterização macroscópica foram escolhidas três formulações para caracterização de espessura, solubilidade, biodegradabilidade, opacidade, conteúdo de água e análise microscópica. Com base nestes resultados foi escolhido o filme para os estudos de incorporação do fármaco (teor e perfil de liberação). Os resultados mostraram que o aspecto macroscópico dos filmes de xilana/gelatina foi melhor que o dos filmes de xilana, isso ocorreu provavelmente devido à alta solubilidade da gelatina. O aumento da concentração de xilana afetou a solubilidade, conteúdo de água, espessura e opacidade dos filmes. O teor de diclofenaco sódico presente no filme foi de 87,88% e a liberação do fármaco se deu principalmente nas primeiras 4 horas, seguida de uma liberação lenta até o final do estudo.

A dissolução de fármacos administrados por via oral é pré-requisito para sua absorção e eficácia clínica. Esta constatação fornece a base para as tentativas de estabelecer correlações entre a dissolução in vitro e a biodisponibilidade in vivo de medicamentos, denominadas correlações in vitro - in vivo (CIVIV). As correlações in vitro-in vivo referem-se ao estabelecimento de uma relação racional entre propriedades biológicas, ou parâmetros derivados destas, produzidas por uma forma farmacêutica, e suas propriedades ou características físico-químicas. O estabelecimento desse tipo de correlação de dados pode possibilitar a substituição dos estudos in vivo, necessários para avaliação da biodisponibilidade de medicamentos, por estudos in vitro, com grandes vantagens éticas e econômicas. A probabilidade de obtenção de correlação in vitro-in vivo é maior quando o processo limitante da absorção do fármaco é a dissolução, o que ocorre para medicamentos contendo fármacos de classe biofarmacêutica II (baixa solubilidade e alta permeabilidade) e para sistemas de liberação controlada de fármacos. O diclofenaco de sódio (DFS) é um fármaco que possui ampla absorção através do intestino (próximo a 100%) e baixa solubilidade em pH abaixo de 6,0, o que o inclui na classe II do SCB. Caracteriza-se como antiinflamatório não esteroidal, com atividades analgésica e antipirética. Considerando as características físico-químicas e farmacológicas do DFS, é objetivo deste trabalho desenvolver e realizar uma validação interna e externa de correlação CIVIV para formulações contendo este fármaco. Para o desenvolvimento e validação interna de CIVIV, foram empregados comprimidos matriciais de DFS contendo o excipiente hidroxipropilmetilcelulose (HPMC) como agente controlador da liberação do fármaco. Três formulações de DFS contendo HPMC em diferentes concentrações (com diferentes taxas de liberação do fármaco) foram avaliadas em estudo de dissolução. Os dados de fração absorvida, obtidas pelo método de deconvolução (MOURÃO, 2009), foram plotados diretamente com os dados de fração dissolvida, obtendo um CIVIV com determinação linear de 0,9738. Para a validação externa, o modelo de CIVIV obtido (intercepto e inclinação) foi utilizado para prever os dados de fração absorvida a partir dos dados de dissolução, empregando três formulações comerciais de DFS. Os resultados de absorção foram extrapolados pelo método de convolução para a obtenção da curva plasmática prevista. Os dados da curva plasmática prevista foram comparados aos dados da curva real de DFS, obtidas no estudo de biodisponibilidade, e os erros de predição (EP%) entre as curvas, foram estabelecidos para a validação externa. Uma CIVIV de nível C foi estabelecida entre diversos parâmetros, empregando as formulações matriciais de DFS e as formulações comerciais. De acordo com os resultados de nível C obtidos, a metodologia de dissolução proposta pode ser empregada para o desenvolvimento de novas formulações contendo o fármaco DFS. / The dissolution of drugs administered orally is a pre-requisite for its absorption and clinical effectiveness. This finding provides the basis for attempts to establish correlations between in vitro dissolution and in vivo bioavailability of drugs, called correlations in vitro-in vivo (IVIVC). The correlation between in vitro-in vivo refers to the establishment of a rational relationship between biological properties, or parameters derived from those produced by a pharmaceutical form and its properties or physicochemical characteristics. The establishment of this type of correlation data may allow the replacement of in vivo studies necessary to evaluate the bioavailability of drugs, for in vitro studies with high ethical and economic advantages. The probability of obtaining correlation in vitro-in vivo is greater when the process of limiting drug absorption is dissolution, which occurs for drug products containing drugs biopharmaceutical class II (low solubility and high permeability) and controlled release systems drugs. Diclofenac sodium (DFS) is a nonsteroidal anti-inflammatory drug with analgesic and antipyretic properties. The objective of this work is to develop and implement an internal and external validation correlation IVIVC for formulations of DFS. For the development and internal validation of IVIVC were employees of DFS matrix tablets containing the excipient hydroxypropyl methylcellulose (HPMC) as a controlling agent drug release. Three formulations containing DFS in HPMC at different concentrations (with different rates of drug release) were evaluated in a study of dissolution. The absorbed fraction data obtained by the deconvolution method (MOURÃO, 2009), were plotted directly with the dissolved fraction data, obtaining a linear IVIVC with determination of 0.9738. For external validation, the obtained IVIVC model (intercept and slope) was used to predict the fraction absorbed data from dissolution data using three commercial formulations of DFS. The absorption results were extrapolated by the method of convolution to obtain the expected plasma curve. The plasma curve data were compared to data provided in real DFS curve, obtained in the bioavailability study, and the prediction error (PE%) between the curves were established for external validation. A level C IVIVC has been established between various parameters, using the matrix formulations of DFS and commercial formulations. According to the results obtained from C-level, the methodology proposed dissolution can be used to develop new drug formulations containing the DFS drug.

As evidências da contaminação das águas por resíduos de medicamentos e seus subprodutos levou esse grupo de resíduos a compor a lista de poluentes orgânicos emergentes, como consequência da expansão do uso de medicamentos, como o antidepressivo cloridrato de fluoxetina e o anti-inflamatório diclofenaco. Diversos Processos Oxidativos Avançados vêm sendo aplicados para a degradação destes compostos. Dentre eles, o processo de irradiação com feixe elétrons obteve bons resultados na remoção de toxicidade e degradação de fármacos. O presente estudo consistiu em aplicar radiação ionizante como uma possível tecnologia para degradar os fármacos em águas. A irradiação de solução aquosa contendo os fármacos foi aplicada usando acelerador de elétrons, cuja eficiência foi discutida mediante análises químicas (Cromatografia Líquida Ultra Rápida e Carbono Orgânico Total (COT)), ecotoxicológicas (ensaios de toxicidade com Vibrio fischeri e Daphnia similis) e biológicas (Ensaios Respirométricos). Os resultados de COT indicaram mineralização não significativa dos compostos, mesmo sendo observada degradação máxima de 99,9% para o diclofenaco e 55% para o cloridrato de fluoxetina na mistura (1:1) em 5.0 kGy. Foi observada toxicidade aguda dos fármacos, sendo mais acentuada para a fluoxetina, seguido do diclofenaco e, finalmente, da mistura para V. fischeri. Quando D. similis foram empregadas nessa avaliação, a ordem de toxicidade foi de fluoxetina, a mistura de ambos os medicamentos e do diclofenaco. Além disso, foi observada remoção de toxicidade nas amostras irradiadas em todas as doses aplicadas para a bactéria V. fischeri, com maior eficiência de remoção de toxicidade de 55%, em 5 kGy, na mistura dos dois fármacos. Para a D. similis, foi observada remoção significativa de toxicidade da mistura apenas na dose 2,5 kGy. Os ensaios respiroétricos não indicaram biodegradabilidade após o tratamento. / The evidence of water contamination by pharmaceuticals and byproducts residues took them to the list of wastewater emerging organic pollutants, as a result of expansion in drug usage. Fluoxetine hydrochloride antidepressant and diclofenac anti-inflammatory are good examplex. Several Advanced Oxidation Processes have been applied for degradation of these compounds. Among them, the electron beam irradiation process obtained good results in the removal of toxicity and degradation of pharmaceutical. The present study aimed to apply ionizing radiation as a possible technology to degrade the pharmaceutical in water. Irradiation of aqueous solution containing the pharmaceutical was applied using electron accelerator, whose efficiency was discussed through Chemical Analysis, COT, ecotoxicological (Toxicity Testing using Vibrio fischeri and Daphnia similis) and biological measurements (respirometric tests). The COT results indicated not significant mineralization of the compounds. It was observed maximum degradation of 99.9% for diclofenac and 55% for fluoxetine hydrochloride in a mixture solution (1:1) at 5.0 kGy. Regarding ecotoxicity, acute effects were more pronounced for fluoxetine, followed by diclofenac and finally the mixture, to Vibrio fischeri. When Daphnia similis were exposed fluoxetine was more toxic, followed by the mixture of both products and the third was diclofenac. Furthermore, radiation effects for removing toxicity was more effective with V. fischeri bacterium, all applied doses and > 55% removal of toxicity at 5 kGy (in the mixture). To D. similis, toxicity removal was effective when treated with 2.5 kGy ( mixture). No improvements in biodegradability was obtained by radiation ( respirometric tests).

Drug based nanoparticle (NP) formulations have gained considerable attention over the past decade for their use in various drug delivery systems. NPs have been shown to increase bioavailability, decrease side effects of highly toxic drugs, and prolong drug release. Furthermore, polymer based, biodegradable nanodelivery has become increasing popular in the field of NP formulation because of their high degree of compatibility and low rate of toxicity. Due to their popularity, commercially available polymers such as poly lactic acid (PLA), poly glycolic acid (PGA) and polylactic-co-glycolic acid (PLGA) are commonly used in the development and design of new nano based delivery systems. Nonsteriodal anti-inflammatory drugs (NSAIDs) are commonly used for the treatment of pain and inflammation. NSAIDs such as diclofenac and celecoxib function by blocking cyclooxygenase expression and reducing prostaglandin synthesis. Unfortunately, the pharmacological actions of NSAIDs can lead to the development of several adverse side effects such as gastrointestinal ulceration and bleeding. The aim of this study was to formulate and optimize diclofenac or celecoxib entrapped polymer NPs using an emulsion-diffusion-evaporation technique. NP formulations were evaluated based on specific formula parameters such as particle size, zeta potential, morphology, and entrapment efficiency. Effects of stabilizer type, stabilizer concentration, centrifugal force, drug amount, and/or emulsifier (lecithin) on nanoparticle characterization were examined for formula optimization. Results of the formulation studies showed that NPs developed using polylactide-co-glycolide (PLGA) polymers and the stabilizer didodecyldimethylammonium bromide (DMAB) demonstrated enhanced stability, drug entrapment, and reduced particle size. These findings demonstrate an effective method for polymer NP formulation of diclofenac or celecoxib. Furthermore, the results reported herein support a novel method of drug delivery that may function to reduce known adverse effects of these pharmacotherapeutic agents.

<p>Cardiovascular disease (CVD) is the major cause of death in patients with chronic renal failure (CRF). Endothelial function and oxidative stress (OS) have previously been shown to be important in the pathogenesis of CVD. In this thesis, the endothelium-dependent vasodilatation (EDV) and OS were investigated in the patients with CRF. Also the influence of L-arginine, erythropoietin and diclofenac on EDV were evaluated in patients with CRF. </p><p>Patients with CRF were found to be characterized by a defect EDV even after correction for traditional cardiovascular risk factors. This impairment was related to the degree of renal failure. </p><p>Measurement of OS markers in CRF patients demonstrated that these patients were in a state of OS compared to healthy controls. The most informative indices to evaluate the degree of OS in CRF were: oxidized glutathione (GSSG) level, ratio between oxidized and reduced glutathione (GSSG/GSH ratio), lag phase of lipoprotein fraction (LPF) and baseline diene conjugation level of LPF. </p><p>Simultaneously investigated OS markers and EDV demonstrated a relationship between OS and EDV in patients with CRF. EDV was positively correlated with total antioxidative activity, reduced glutathione (GSH) and lag phase of LDL. </p><p>Local infusion of L-arginine as a substrate for nitric oxide synthesis and diclofenac as an inhibitor of cyclooxygenase-derived vasoconstrictive agents augmented EDV in patients CRF. In contrast, the erythopoietin treatment (both acute and long-term) impaired EDV in CRF patients. </p><p>In conclusion, patients with CRF have increased levels of OS markers and impaired endothelial vasodilatory function. These factors may be important with respect to the high morbidity and mortality of CVD found in patients with CRF. One possible mechanism to reduce CVD in patients with CRF is to improve endothelial function and eliminate OS. Locally administrated L-arginine and diclofenae improved EDV but erythropoietin administration impaired EDV in patients with CRF. </p>

Cardiovascular disease (CVD) is the major cause of death in patients with chronic renal failure (CRF). Endothelial function and oxidative stress (OS) have previously been shown to be important in the pathogenesis of CVD. In this thesis, the endothelium-dependent vasodilatation (EDV) and OS were investigated in the patients with CRF. Also the influence of L-arginine, erythropoietin and diclofenac on EDV were evaluated in patients with CRF. Patients with CRF were found to be characterized by a defect EDV even after correction for traditional cardiovascular risk factors. This impairment was related to the degree of renal failure. Measurement of OS markers in CRF patients demonstrated that these patients were in a state of OS compared to healthy controls. The most informative indices to evaluate the degree of OS in CRF were: oxidized glutathione (GSSG) level, ratio between oxidized and reduced glutathione (GSSG/GSH ratio), lag phase of lipoprotein fraction (LPF) and baseline diene conjugation level of LPF. Simultaneously investigated OS markers and EDV demonstrated a relationship between OS and EDV in patients with CRF. EDV was positively correlated with total antioxidative activity, reduced glutathione (GSH) and lag phase of LDL. Local infusion of L-arginine as a substrate for nitric oxide synthesis and diclofenac as an inhibitor of cyclooxygenase-derived vasoconstrictive agents augmented EDV in patients CRF. In contrast, the erythopoietin treatment (both acute and long-term) impaired EDV in CRF patients. In conclusion, patients with CRF have increased levels of OS markers and impaired endothelial vasodilatory function. These factors may be important with respect to the high morbidity and mortality of CVD found in patients with CRF. One possible mechanism to reduce CVD in patients with CRF is to improve endothelial function and eliminate OS. Locally administrated L-arginine and diclofenae improved EDV but erythropoietin administration impaired EDV in patients with CRF.

The aim of the present study was to formulate oral modified release matrices of diclofenac sodium, using the Eudragit® polymers. In addition to the formulation processes, numerous variables had to be investigated, which included dissolution variables, formulation variables, and processing variables. The application of the tabletting technique as well as the use of Eudragit® polymers to modify the release of diclofenac sodium is motivated at the outset. A comprehensive review of modified drug release, the use of the tabletting methodologies and the application of Eudragit® polymers are presented. In-process quality control tests as well as the mechanisms and interpretation of the dissolution process are outlined. Diclofenac sodium, a potent nonsteroidal anti-inflammatory drug, was used in the present study, hence a brief review of this drug is also presented. The direct compression as well as the wet granulation tabletting methods were investigated. The major limitation of the direct compression method was found to be the lack of suitable flow properties of the powder blend. The wet granulation technique however, was successfully employed to prepare various diclofenac sodium Eudragit® matrix tablets. All tablets were prepared to contain 100 mg diclofenac sodium. The optimisation process was shown to be an integral procedure in influencing the matrix characteristics. In addition, it was shown that drug release was significantly influenced by different types and concentrations of Eudragit® polymers. A specific formulation was selected to investigate the integrity of the matrices produced by the wet granulation technique. The drug release profile of a commercially available modified release preparation containing diclofenac sodium viz. Veltex® 100 CR (reference standard) was also obtained. A comparison of the drug release profiles of Veltex® 100 CR capsules and the selected formulation showed them to be markedly dissimilar. Hence, a strong motivation is provided for rationalising the selection of the particular formulation in the present study, that was shown to release diclofenac sodium optimally. The selected formulation was prepared using a combination of the Eudragit® RL and Eudragit® RS polymers. In vitro dissolution studies on the selected as well as various other formulations demonstrated the wet granulation method to be both predictable and reproducible. However, absolute drug release independency of dissolution methods, media and agitation rates was unattainable. Furthermore, drug release was shown to be pH dependent. The selected formula was subjected to certain formulation and processing variables. An increase in the concentrations of lactose and starch was shown to increase drug release. Different types of diluents were also shown to influence drug release from the tablets. The method of incorporation of the lubricant, magnesium stearate, was investigated. Compression studies demonstrated the susceptibility of the tablets to changes in drug release behaviour and morphological characteristics as the hardness was varied. X-ray diffraction studies demonstrated that the processes of granulation and compression did not promote any atomic rearrangement of the drug and Eudragit® polymers. Scanning electron microscopy was useful in investigating the integrity and surface morphology of newly formulated as well as stored samples, while energy dispersive x-ray microprobe analysis adequately revealed the elemental composition of the tablets. The selected formulation was shown to be stable at room temperature (21 ±1°C) and low temperature (5± 1°C), while storage at 37°C with 80% relative humidity and 40°C demonstrated significantly decreased drug release behaviour during short term (3 months) stability testing. Tablet hardness evaluated during the stability testing showed that there were virtually no differences in tablet hardness between the room temperature and low temperature samples, while tablets stored at 37°C with 80% relative humidity and 40°C hardened considerably. However, tablet potencies and the moisture content of the samples were not significantly influenced during the storage period. In addition to usual observations and mathematical manipulation, some of the data generated from this study were also evaluated statistically. / Thesis (M.Sc.)-University of Durban-Westville, 1998.

L'objectif de ce travail de thèse est d'étudier la relation entre la méthode de préparation des nanoparticules, les propriétés colloïdales et l'encapsulation d'un principe actif à usage pédiatrique. Dans ce but, le diclofenac a été utilisé comme molécule modèle et les nanoparticules ont été préparées via la nanoprécipitation et l'émulsification-diffusion. Des études fondamentales et systématiques ont permis de mettre en évidence l'existence de différences notables entre les propriétés électrocinétiques et l'efficacité d'encapsulation en fonction du procédé utilisé pour la préparation des particules. Ces propriétés colloïdales et physico-chimiques sont primordiales pour la bonne stabilité des dispersions de nanosphères et des nanocapsules et pour le comportement de ces vecteurs lors d'utilisation in vivo. Cette étude a permis de proposer et de discuter le mécanisme de formation des nanoparticules en se basant sur le comportement des variables critiques du procédé et de la formulation, les propriétés de surface et l'efficacité d'encapsulation de l'actif modèle