Дисертації з теми "Préparation de médicaments"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 дисертацій для дослідження на тему "Préparation de médicaments".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте дисертації для різних дисциплін та оформлюйте правильно вашу бібліографію.
Roussel, Sabrina. "Alternative au polyéthylène glycol dans la préparation de vecteurs pharmaceutiques." Master's thesis, Université Laval, 2021. http://hdl.handle.net/20.500.11794/70302.
Повний текст джерелаFor a long time, polyethylene glycol (PEG) has been considered as biologically inert, but it is now clear that not only antiPEG antibodies do exist , but also, they can be widespread in the general population. Currently, the mechanism by which these antibodies bind to the plasmatic proteins is still under investigation. However, they are responsible for the phenomenon of accelerated blood clearance and some adverse effects such as hypersensitivity and anaphylaxis. Moreover, recent studies suggest that 7% of the population pre-exposed (72%) to PEG have a high level of antibodies (immunoglobuline G ˃ 500 ng/mL), making them susceptible to allergic reactions.¹ ² Among other things, 6 out of 272 000 people did suffer from anaphylaxis during the injection of Pfizer-BioNTech's COVID-19 vaccine last December, potentially because of the presence of PEG in the formulation. It is therefore very important as we develop therapeutic modalities using polymers, to assess their effects in vivo. Several alternatives have been proposed to PEG such as polyvinylpyrrolidone, poly(N-isopropylacrylamide), poly(glycerol) and poly(2-oxazoline). Unfortunately, to date none of these polymers have yet succeeded reaching the FDA approved PEG standard. The objectives of this study were initially to synthesise a polymer which could potentially replace PEG on the surface of pharmaceutical vectors such as liposomes or nanoparticles. An amphiphilic polymer based on monoglycerol acrylate was incorporated into a liposome formulation. Secondly, the anchoring of this polymer to the surface of our vector was evaluated using several techniques. Our results demonstrate that the amphiphilic character, created by one or many alkyl chains is important, and it influences drastically the anchoring of the polymer into the bilayer but also the pharmacokinetic (PK) of the nanocarrier.
Chrétien, Christophe. "Embolisation : préparation et évaluation de microsphères pour une chimiothérapie locale." Paris 5, 2004. http://www.theses.fr/2004PA05P636.
Повний текст джерелаTherapeutic efficiency of embolization is enhanced by the locoregional delivery of a drug at the embolization site. Therefore, the macroporous network of microspheres designed for embolization was impregnated with calcium alginate to transport and control the release of different drugs. The impregnation of ion-exchange microspheres allowed the controlled release of drugs coupled to the microspheres. The release rate of indomethacin was reduced, highlighting the formation of a calcium alginate gel inside the macroporous microspheres. On the other hand, the diffusion rate of oligonucleotides coupled to the impregnated ion-exchange microspheres was reduced. The impregnation of macroporous microspheres allowed the transport of high molecular weight compounds and their controlled release. The impregnation process was optimized leading to increased amounts of alginate impregnated in the microspheres, to higher encapsulation efficiencies of the compounds and to their lagged release
Feutry, Frédéric. "Étude des interactions physico-chimiques entre les préparations parentérales et un nouveau conditionnement primaire utilisable en unité de préparation centralisée, le flacon Crystal®." Thesis, Lille 2, 2016. http://www.theses.fr/2016LIL2S021.
Повний текст джерелаCentralized preparation of parenteral products in the pharmacy can ensure a higher quality but requires a stability of the drugs in the chosen primary packaging and a sufficient production capacity. Aseptic Technologies has developed an automated primary packaging filling system using a closed, sterile and ready-to-use cyclic olefin copolymer vial called ‘‘Crystal® vial’’. This vial is filled through the elastomeric septum and then immediately re-sealed by laser, thus reducing the risk of microbial contamination.We have evaluated risks linked to the use of Crystal® vials:- Sorption risk is correlated with substance lipophilicity. During 3 months, we have evaluated concentration evolution of 8 cytotoxic drugs (with different water/octanol partition coefficients) by HPLC/MS. Same methodology was used to measure concentration evolution of 3 platinum-derived drugs by NMR during 24 hours.- About the permeation risk, we have evaluated concentration evolution of phenol and metacresol in a 1UI/mL insulin solution during 50 days by HPLC/UV in Crystal® vials stored upright and upside down. Two stoppers formulations exist and were tested.- Extreme pH solutions can lead to the presence of particles in the parenteral product. Impact of these solutions in Crystal® vials on particles contamination was studied and particles characterized.- Plasticizers may migrate from the primary packaging to the parenteral products. After isopropanol reflux extraction on the COC body and thermoplastic elastomer stopper, potential plasticizers were identified and quantified using NMR.Finally, stabilities of ready-to-use cefuroxime, midazolam and noradrenaline solutions in Crystal® vials were determined and compared to polypropylene syringes.The 8 cytotoxic drugs mean concentrations were between 90% and 110% at day 62 with no correlation with partition coefficient. Lack of interactions was demonstrated too for the oxaliplatin and carboplatin solution by NMR. Accuracy of NMR cisplatin quantification was not sufficient.Studies performed on preservatives highlighted a metacresol permeation risk during storage at 25°C/60%RH for 50 days (loss of 19.7% and 20.3% respectively for Crystal® vials stored upright and upside down). Use of the second formulation stopper allowed a large decrease of permeation (loss of 2.6% at day 50).An important particles contamination was observed only with extrem alkaline pH and contact with the stopper (6820 particles 10µm in a 20mL Crystal® vials stored upside down during 7 days). Particles are fibrous and essentially composed by non-organic substances.NMR analysis highlighted presence of plasticizers in both COC body and elastomer stopper but concentrations were below the 1000µg/g threshold described by the REACH regulation.Cefuroxime solution (1mL at 10mg/mL) was stable 365 days at -20°C. Midazolam solution (50mL at 1mg/mL) and noradrenaline solution (20mL and 50mL at 0.2mg/mL ; 50mL at 0.5mg/mL) were stable 365 days at 5°C. Same results were achieved in polypropylene syringes.Crystal® vials were not subject to sorption phenomena. There was no risk of plasticizer migration. Metacresol permeation risk was controlled using the new stopper. Packaging of alkaline solution must be monitored. Solutions of cefuroxime (-20°C), midazolam and noradrenaline (5°C) are stable 1 year. In regards to storage in polypropylene syringes, Crystal® vials could be prefered for their automated aseptic filling process and for logistic considerations particularly taking into account the space gains
Martinez, Leticia. "Application du procédé de prilling pour la préparation de micro-réseaux à base de chitosane." Paris 11, 2004. http://www.theses.fr/2004PA114830.
Повний текст джерелаChitosan is a natural, biodegradable, and biocompatible polymer. Chitosan based pH-sensitive hydrogels are promising systems for the preparation of controlled drug delivery pharmaceutical forms. Meanwhile, divided solid dosage forms appear to comply to pharmaceutical and industrial requirements in terms of quality, safety, and process optimization. Ln this work, we prepare semi-interpenetrated chitosan/poly(ethylene oxide) micro networks by a prilling process. The physico-chemical characterization of the obtained divided systems, called prills, reveal spherical particles with calibrated diameter and narrow size distribution. The structure of the micro networks is achieved thrOUgh the study of chitosan chains crosslinking. Ln an acid environment, micro networks present great swelling capacities. These properties can be applied to the formulation of orally administrated drugs
Heurtault, Béatrice. "Développement d'un procédé de préparation d'une nouvelle génération de nanocapsules lipidiques." Paris 11, 2002. http://www.theses.fr/2002PA114819.
Повний текст джерелаKhoury, Madona. "Préparation, analyse et activités antimicrobiennes d'huiles essentielles de plantes libanaises." Paris, Muséum national d'histoire naturelle, 2015. http://www.theses.fr/2015MNHN0024.
Повний текст джерела@Inspired by plant defenses, we undertook to evaluate the chemical diversity and antimicrobial activities of essential oils (EOs) from Lebanese plants. Following a metabolomic approach we were able to highlight the chemical diversity among the 32 studied oils and between the chemotypes of the same plant species. The screening led to the identification of several EOs with interesting antimicrobial activities. Hirtellina lobelii DC. EO was among the most active ones, alone or in combination with antimicrobial drugs. This oil holds remarkable antifungal potential against dermatophytic fungi by disrupting fungal membrane and ultimately leasing cells. We hypothesized that H. Lobelii EO should increase cell penetration of antifungal drugs and may also act through a specific mode of action. Altogether, these results lead us to believe that plant defense arsenal can inspire alternative ways of addressing the societal issue of multidrug resistant infections
Galindo, Rodriguez Sergio Arturo. "Étude comparative de trois techniques de préparation de nanoparticules à base de polymères : physico-chimie, efficacité d'encapsulation et transposition d'échelle." Lyon 1, 2004. http://www.theses.fr/2004LYO10221.
Повний текст джерелаBerrada, Ai͏̈da. "Préparation du lancement d'un générique de marque dans le domaine de la douleur sur le marché pharmaceutique marocain." Paris 5, 1999. http://www.theses.fr/1999PA05P062.
Повний текст джерелаKlotz-Masson, Chantal. "De la conception médicale d'un protocole d'étude clinique à sa préparation pharmaceutique." Bordeaux 2, 1992. http://www.theses.fr/1992BOR2P013.
Повний текст джерелаSchammé, Benjamin. "Mobilité moléculaire, mécanismes de cristallisation et stabilité physique de composés pharmaceutiques amorphes : impact des méthodes de préparation." Rouen, 2016. http://www.theses.fr/2016ROUES049.
Повний текст джерелаAmorphous pharmaceuticals (excipients and active ingredients) are considered as one of the most promising approach to overcome the poor water solubility issue related to many drug molecules. Preparing poorly soluble drugs in the amorphous state is thus becoming an essential strategy for incorporating drugs into highly effective dosage forms. Recent developments have highlighted the need of a better understanding of the impact of preparation pathway onto the resulting amorphous solids. The aim of this thesis is to contribute to a rational knowledge of the differences in the amorphous state generated by two distinct preparation pathways: quenching from the melt and high-energy milling. Physico-chemical properties of the amorphous materials were studied using a set of analytical methods (structural, thermal and spectroscopic) coupled to quantum DFT calculations. It was demonstrated for two compounds of pharmaceutical interest that depending on the preparation methods, properties such as physical stability and crystallization kinetics might differ, leading to distinct behaviors upon storage. Melt-quenched states have been found to possess a good stability over time, while milled ones exhibit a lower stability resulting in an easier tendency toward crystallization. Moreover, beyond the glass transition temperature, it was outstanding to note that all discrepancies in physico-chemical properties are suppressed. Our findings indicate also that the propensity of both inspected molecular compounds to be amorphized rises as milling temperature decreases. This thesis also provides new insights to elaborate adequate stabilization protocols for amorphous pharmaceuticals
Semetey, Vincent. "Vers la préparation de vaccins synthétiques administrables par voie nasale : Oligomères d'urées N,N'-liées:synthèse,étude conformationnelle et propriétés d'auto assemblage." Université Louis Pasteur (Strasbourg) (1971-2008), 2002. http://www.theses.fr/2002STR13238.
Повний текст джерелаThe search for new nonnatural oligomers ("foldamers") designed to reproduce or mimic the secondary structure of peptide (helix, sheet, turn) have gained considerable interest with potential application in pharmaceutical research. Work published by the groups of Seebach, Gellman and Hanessian has revealed that short peptides made exclusively with enantiopure or -amino acids, correctly substituted, could form in solution and in the solid state, stable helical or pleated-sheet-type structures. This memory of thesis is devoted to the synthesis and the conformational study of linear and cyclic N,N'-linked urea oligomers. The linear N,N'-linked urea oligomers have a strong analogy with peptides. However, their conformational preference as their folding propencity were not yet studied. A simple and effective method was developed to obtain succinimidyl carbamates derivatives starting from -amino acids. These carbamates are stable and crystalline compounds that react spontaneously with amines at ambient temperature to afford corresponding ureas. These precursors were used for the synthesis of linear N,N'-linked urea oligomers using solid phase methodology. The conformational study in solution of this family of oligomers performed by NMR in pyridin-d5 as well as by circular dichroism shows that these oligomeric molecules adopt a helicoidal secondary structure. On the basis of this structure, urea oligomers presenting an antibacterial activity were designed and synthesized. The succinimidyl carbamate derivatives were also used for the synthesis of cyclic N,N'-linked urea oligomers in solution. The assembly properties of these compounds were analysed in the solid state. The X-ray cristallography studies of the tetramer reveal the formation of strongly polarized tubular structures
Roche, Marine. "Développement de méthodes analytiques pour l'étude de la stabilité et de la compatibilité de médicaments sous forme de solution ou de systèmes dispersés. Application en anesthésie-réanimation." Electronic Thesis or Diss., Université de Lille (2022-....), 2024. http://www.theses.fr/2024ULILS021.
Повний текст джерелаThe research subject of this PhD focused on the development of analytical methods to assess the stability or incompatibilities of injectable anaesthetic drugs in solution or in dispersed systems.The first part of this work involved a study of the stability of cisatracurium besylate ampoules produced by the pharmacy of Lille University Hospital to ensure continuity of care for intensive care patients in the context of supply disruptions caused by the COVID-19 pandemic. The stability study was conducted on a batch of 4,000 ampoules stored at 2-8°C for 18 months. This study required the validation of a stability-indicating HPLC-UV method for the determination of cisatracurium and laudanosine, one of its degradation products described as a marker of its instability. In addition, the use of an HPLC-mass spectrometry method enabled the identification of degradation products and the study of degradation pathways. Our results showed that cisatracurium solutions at 10mg/mL were stable for 15 months under our preparation and storage conditions. The main degradation pathway observed under our study conditions (ester hydrolysis) differed from that previously described (Hofmann pathway). This highlights the imponderability of conducting stability studies under conditions representative of the actual use of drugs. The second part of this thesis led us to study the incompatibility between different drugs used in anaesthesia and intensive care units. The models studied were the simultaneous administration of propofol and alpha-2 adrenergic receptor agonists (α2A; clonidine or dexmedetomidine) used in multimodal analgesia. The data available in the literature refers to concentrations and ratios that are not representative of those encountered in hospital wards, potentially exposing patients to drug hazards. We assessed the compatibility of propofol-α2A combinations under conditions mimicking those encountered in critical care units. Eight conditions per combination were evaluated over 96 hours, in triplicate, varying the simulated mass flow rates for each drug and for patient weights of 45 and 150 kg. To assess the chemical compatibility of these combinations, we developed and validated 3 stability-indicating HPLC-UV assay methods to study the stability of propofol, clonidine and dexmedetomidine in combination for 96 hours. The physical compatibility of the emulsion in combination was assessed using a granulometer coupled to a zeta potential measurement (with positive and negative controls). Our results demonstrated the physico-chemical stability of propofol-α2A mixtures representative of those used in current practice.In conclusion, the results of this work have provided scientific validation of hospital pharmacy and care service practices. They also highlighted the fundamental role of pharmacists in guaranteeing the quality of patient drug management, by using their skills in analytical chemistry to assess compatibility and stability data
Pourageaud, Fabrice. "Role modulateur de l'endothélium sur les propriétés fonctionnelles d'une préparation d'artère coronaire perfusée de rat SFR : effets d'un inhibiteur de l'enzyme de conversion." Bordeaux 2, 1995. http://www.theses.fr/1995BOR28352.
Повний текст джерелаPassive and active properties were studied in perfused coronary arteries of WKY rats, SHRs and SHRs treated rats with an angiotensin converting enzyme inhibitor, trandolapril. Concerning passive properties, it has been shown that direct smooth muscle cell activation or NO synthesis inhibition induced an increase in distensibility of rat coronary arteries. In SHR preparations, distensibility was significantly less compared to that in WKY arteries. Moreover, a treatment with trandolapril improved distensibility of SHR coronary arteries. As concerne studies of the active properties, an anterograde flow in preconstricted preparations induced a dilation which was essentially endothelium-dependent. In contrast, a retrograde flow increased constriction level and this effect was completely dependent on the presence of the endothelium. The maximal dilations induced by endothelium-dependent agonists such as acetylcholine or bradykinin were weaker in coronary arteries of SHR compared to those of WKY arteries. Moreover, flow induced dilations were also impaired in SHRs compared to WKY preparations. Maximal dilations induced by endothelium-independent agonist were not dignificantly different in arteries of both strains. Treatment with trandolapril improved endothelium dependent dilations induced by acetylcholine and bradykinin whereas the flow-induced dilation was not significantly different in arteries of both groups. From these results, trandolapril improved intrinsic elastic properties of SHR coronary arteries but also endothelium -dependent dilations induced by the two agonists. However, the flow-induced dilation seemed to remain unaffected
Ablise, Mourboul. "Préparation et évaluation in vitro de l'activité anti-oxydante d'extraits et de principes actifs (naturels et synthétiques) de plantes médicinales chinoises : liens éventuels avec le vieillissement et la longévité." Nancy 1, 2004. http://www.theses.fr/2004NAN12503.
Повний текст джерелаGally, José-Manuel. "Développement d'outils de chémoinformatique pour l'identification d'inhibiteurs de protéines kinases à partir de fragments." Thesis, Orléans, 2017. http://www.theses.fr/2017ORLE2033.
Повний текст джерелаDrug design is a long and complex multidisciplinary process. From the discovery of the initial hit (bioactive molecule), to the lead (optimized compound), and finally to the commercialization of the end product (drug), almost 10 years are necessary and this process costs an average of $1 billion dollars. In order to optimize this process, new methods are relentlessly developed so that novel promising molecules might be identified faster for a given target. Protein kinases (PK) play a central role in most molecular pathways and are essential to control cellular mechanisms. The mutation of one PK can lead to severe pathologies such as neurodegenerative diseases or cancer, making the research of PK inhibitors (PKI) an intense area of therapeutic research. In this manuscript, two complementary chemoinformatics approaches are discussed for identifying PKI, and both depend on the preparation of small molecules (ligands). For this specific task, a new workflow protocol, VSPrep, was developed using only freely available tools for academics. First, a virtual screening approach of natural products was performed in order to identify bioactive molecules for cosmetics or therapeutic applications. Second, a novel in silico Fragment-Based Drug Discovery (FBDD) tool, Frags2Drugs, was developed specifically for kinase research. It combines molecular fragments derived from PKI into novel inhibitors bound to specific protein kinases. The tool was validated on several internal kinase projects leading to novel protein kinase inhibitors with acceptable drug-like properties
Lehmann, Hélène. "Le médicament à base de plantes en Europe : statut, enregistrement, contrôles." Phd thesis, Université de Strasbourg, 2013. http://tel.archives-ouvertes.fr/tel-00936734.
Повний текст джерелаDuterme, Jean Marie. "Matières plastiques et préparations injectables : interactions." Paris 5, 1988. http://www.theses.fr/1988PA05P039.
Повний текст джерелаBourget, Guillemette. "Contribution à l'étude des propriétés cytotoxiques, antitumorales et hémolytiques d'un extrait aqueux d'une éponge : Pachymatisma Johnstonii." Nantes, 1989. http://www.theses.fr/1989NANT08VS.
Повний текст джерелаMartinez, Teran Maria Esther. "Development and evaluation of controlled release pellets in orodispersible tablets for pediatric use." Thesis, Lille 2, 2016. http://www.theses.fr/2016LIL2S051/document.
Повний текст джерелаIn the last decade, medical agencies have promoted a pediatric regulatory focusing on the development and availability of age-appropriate formulations suitable for age, size, physiological condition and treatment requirements for the pediatric population. In general, oral drug delivery is still preferred over the other drug delivery routes since it is convenient, economical and user friendly. In recent years, a number of new solid oral drug delivery platforms such as orodispersible tablets have been developed as they are easy to administer, do not require additional water and, as long as dispersion is rapid, the bioavailability of the drug can be significantly greater than those observed in conventional tablet dosage forms offering a potential alternative for pediatric patients. In parallel, multiparticulate products present many advantages compared to single-unit dosage forms as they distribute fast through the gastrointestinal tract, thus reducing local irritation caused by the active ingredient, enhancing drug absorption and decreasing fluctuation of plasma peaks. Moreover, it is possible to control the drug release rate, resulting in fewer adverse effects. Only few studies have dealt with the compaction of uncoated pellets, which potentially could provide fewer problems during compaction than coated pellets, in particular by reducing damages on the coating.The overall objective of this study was to develop a Multiple-Unit Pellet Orodispersible Tablet (MUP-ODT) allowing for the controlled release of acetaminophen (APAP), used as a model drug, which is contained in the pellets of the orodispersible tablets.The first part determined the mechanical properties of APAP pellets produced by the extrusion-spheronization technique containing different types of excipients and different drug load percentages to produce a controlled release matrix system.The second part of this study examined the feasibility to compress uncoated free drug MCC pellets with different orodispersible formulations to assess the influence of the percentage of pellets, type of disintegrants and compression force.The third part was dedicated to produce MUP-ODTs which allowing for controlled-release of APAP using different percentages of Eudragit® to create the matrix system without significant changes in the release profile after compression.Finally, a design of experiments was carried out to determinate the optimal parameters to produce MUP-ODTs.Taste-masking evaluation was realized using the electronic tongue. Dissolution test was performed using a syringe pump and small volumes of aqueous medium at low flow rates to mimic the behavior in the mouth of the child.Different polymers were successfully used to produce APAP matrix pellets with different drug loadings. MUP-ODTs were successfully obtained demonstrating their feasible production with good mechanical properties. They enable very fast disintegration and modified release properties, but also offer easy swallowing for children and dose flexibility
Zazempa, Virginie. "Etudes de stabilité de préparations hospitalières : exemples du ganciclovir et des sirops décontaminants." Paris 5, 1995. http://www.theses.fr/1995PA05P167.
Повний текст джерелаDrivaud, Catherine. "Contribution à l'étude des préparations magistrales prescrites à l'officine." Paris 5, 1991. http://www.theses.fr/1991PA05P167.
Повний текст джерелаPauly, Aude. "Effets inflammatoires et toxiques des préparations ophtalmiques topiques sur la surface oculaire : développement et standardisation de modèles d'évaluation in vitro et in vivo." Paris 5, 2008. http://www.theses.fr/2008PA05P624.
Повний текст джерелаThe REACH program and the future ban to use animals for the toxic evaluation of cosmetics in 2013 impose to revise the classic tools of eye toxicity testing and to develop new approaches. We first used classic in vitro systems to investigate the toxicity of antiallergic eye drops by evaluating the induction of oxidative stress, apoptosis and inflammation. We were so able to connect their toxicity to the presence of benzalkonium chloride (BAC), the common eyedrop preservative used as the irritant of reference in our studies. Then we used flow cytometric analysis of conjunctival brushings, in conjunction with multiple cytokine assays in tears and in vivo confocal microscopy (IVCM) of the cornea as sensitive and noninvasive tools to refine the classical Draize eye test. In the perspective of future multicenter studies, we standardized the use of IVCM by developing a scoring system, based on the corneal thickness measurement and the precise classification of cytological and histological changes, at the level of the epithelial cells, the keratocytes, the endothelial and the vascular cells. This system enables to deliver a gravity score, as an objective numerical value for the assessment of the toxic-induced corneal damage severity. In vitro, using a reconstituted human corneal epithelium model, we developed a new, more sensitive MTT procedure for the evaluation of cytotoxicity, and correlated this method with a panel of immunohistological tests covering inflammatory, as well as apoptotic and proliferative mechanisms
Yang, QiaoWen. "Systèmes polymériques à base de dispersion aqueuse administrés par voie orale pour la libération contrôlée du principe actif." Lille 2, 2009. http://www.theses.fr/2009LIL2S045.
Повний текст джерелаMuschert, Susanne. "Polymeric coatings for solid dosage forms : characterization and optimization." Lille 2, 2008. http://www.theses.fr/2008LIL2S023.
Повний текст джерелаPlumat, Karine. "Fréquence d'utilisation des matières premières remboursables dans la composition des préparations magistrales en Ile-de-France." Paris 5, 1992. http://www.theses.fr/1992PA05P210.
Повний текст джерелаHached, Fahd. "Encapsulation de cellules stromales mésenchymateuses humaines dans les hydrogels polysaccharidiques : potentielle application dans le traitement de l'arthrose." Thesis, Nantes, 2017. http://www.theses.fr/2017NANT1038/document.
Повний текст джерелаExisting drug therapies for osteoarthritis (OA) provide, at best, symptomatic relief from pain and fail to prevent cartilage damage. Mesenchymal Stromal Cells (MSC) have generated interest since they secrete immunomodulatory factors. Direct injection of MSCs in OA suffers major limitations. To overcome these limitations, several studies have proposed to entrap MSC within biomaterials. However, their immunomodulatory properties after encapsulation have not been investigated. In this context, this work aimed to entrap MSC within spherical particles derived from alginate or from silanized hydroxypropyl methylcellulose (Si-HPMC) and to investigate their biofunctionality. First, a protocol of Si-HPMC particles generation was assessed. Alginate and Si-HPMC particles were characterized. Size, diffusion and mechanical properties of generated particles were studied and compared. Secondly, MSC were entrapped within alginate or Si- HPMC. Their viability and their ability to proliferate were evaluated for up to one month after encapsulation. Lastly, the biofunctionality of encapsulated MSC was investigated in order to harness their therapeutic properties for the treatment of OA. In summary, we have shown that: (i) alginate and Si-HPMC particles exhibit different properties; (ii) both alginate and Si-HPMC particles support MSC survival and (iii) MSC encapsulated in alginate or Si-HPMC are sensitive to pro-inflammatory cytokines and respond to this stimulation by increasing their secretion of bioactive factors. These findings are promising for a potential application of encapsulated MSC to OA treatment
Paubel, Pascal. "Achats des produits du domaine pharmaceutique dans les établissements publics de santé : bilan au 30 novembre 2008 des réformes du code des marchés publics : de la tarification à l'activité et de la rétrocession." Lille 2, 2009. http://www.theses.fr/2009LIL20002.
Повний текст джерелаFrench public hospitals use for all purchases (works, supplies, services) the rules of public contracts. These procedures were modified in 2001, 2004 and 2006, with consequences for practices of hospitals buyers. This work presents fundamentals principles of procedures for public contracts and the organization of purchases in french public hospitals. The consequences of all procedures described by the directory of 1th August 2006 are analysed for supply of medicines and medical devices. This work presents also different modes of financing for medicines and medical devices after the reform of payments by results and the reform for distribution of medicines to ambulatory patients. Analysis of consequences of these reforms for purchase of medicines is suggested at November 2008
Duclos, Cartolano Catherine. "Représentation de l'information pharmaco-thérapeutique des résumés des caractéristiques produit des médicaments : apport des méthodes de traitement automatique du langage naturel, développement, validation et utilisation de modèles." Paris 5, 2003. http://www.theses.fr/2003PA05CD01.
Повний текст джерелаCampos, Ligia Maria Moreira de. "Dégradation du sulfate de néomycine en milieu aqueux par le péroxyde d'hydrogène : application à l'étude de stabilité de préparations pharmaceutiques liquides." Paris 11, 1991. http://www.theses.fr/1991PA114838.
Повний текст джерелаAubin, Marlène. "Révéler la chimie des préparations antiques, à usage cosmétique ou médical, impliquant des sels de métaux lourds." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066479/document.
Повний текст джерелаIn the Antiquity, oculists (eye care specialised physicians) mixed mineral, vegetal and animal substances to prepare elaborate solid medicines termed collyria. In an interdisciplinary work, we investigated the chemical composition, the inorganic phases structure and the manufacturing process of such collyria. The implemented analytical techniques were Raman spectroscopy, X-ray fluorescence (XRF) and X-ray diffraction (XRD). The stability of metallic salts based replicas prepared according to ancient texts recipes was studied in order to identify the pristine phases. Four collections of archaeological collyria (Musée Gallo-Romain de Lyon, Musée d’Archéologie Nationale, Cabinet des Médailles de la BnF, Musée Atestino d’Este) were studied on site, using portable devices. A methodology combining XRF and XRD results was developed to quantify the inorganic phases distribution. For the first time, a straight relationship was established between compositions obtained by physico-chemical analysis and ancient recipes
Bonhomme-Faivre, Laurence. "Étude d'une suspension de charbon injectable par vide intratumorale." Paris 11, 1994. http://www.theses.fr/1994PA114821.
Повний текст джерелаBoudzoumou-Nganga, Pierre. "Médicaments à effet rénal administrés chez la mère pendant la gestation : néphrotoxicité éventuelle chez le nouveau-né : modulations pharmacologiques du développement fonctionnel rénal foetal et néonatal chez le rat après exposition in-utero à la Gentamicine ou au Furosémide." Nancy 1, 1990. http://docnum.univ-lorraine.fr/public/SCD_T_1990_0550_BOUDZOUMOU_NGANGA.pdf.
Повний текст джерелаAminoglycosides (gentamicin) antibiotics well-known for their nephrotoxicity; and furosemide, a widely used diuretic, has been reported to induce a delay in the differentiation of renal glomeruli. We were interested to investigate if the developing kidney could be functionally altered in-utero after administration of either these drugs to the pregnant mother. Drugs were given during two keyperiods of pregnancy: days 7-11 (period of organogenesis) and days 14-18 (beginning of glomeruli differentiation) at the dose of 75mg/Kg/day by i. P. Route. The rat strain was WISTAR. Shortly after birth,variations were observed on diuresis, creatinine clearance, U/P creatinine ratio,fractional excretion of water fractional excretion of electrolytes. The gentamicin-induced nephrotoxicity was reversible, the glomerular function being corrected earlier than the tubular urinary concentrating defect. Furosemide seemed to lead to a delay of development of loop of Henle, suggesting a functional adaptation of other segments of tubule, already mature and functionning. Furthermore, our results provide evidences of functional developmental disturbances (altered growth and urinary concentrating defect) in young rats, lately after prenatal exposure to furosemide or gentamicin. In conclusion, drug administration to mother during pregnancy can lead to a detrmental effect upon the kidney of the newborn and of the young animal
Munin, Aude. "Microparticules de composés naturels réticulés par transacylation : mise au point et étude." Thesis, Reims, 2011. http://www.theses.fr/2011REIMP201.
Повний текст джерелаThe study deals with the development of microcapsules from reticulated natural products, for cosmetological applications
Pelayo, Sylvia. "D'une coopération verticale et intégrative à une planification coopérative des actions : le cas de la gestion des prescriptions thérapeutiques hospitalières." Lille 2, 2007. http://www.theses.fr/2007LIL2S045.
Повний текст джерелаDelplace, Céline. "Microparticules à libération contrôlée : nouveaux polymères et importance des conditions de libération." Thesis, Lille 2, 2012. http://www.theses.fr/2012LIL2S007.
Повний текст джерелаPoly(lactic-co-glycolic) acid (PLGA)-based microparticles represent an attractive choice to sustain drug release over periods ranging from a few days up to several months, while ensuring good biocompatibility and complete biodegradability. Recently, tremendous efforts have been devoted to improve the properties of these copolymers by introducing functional groups along the polymeric chain, with the aim of modulating the drug release.On the one hand, the main objective of this work was to investigate the potential application of new functionalized copolymers bearing pendant carboxyl groups (PLA-co-PBED), as controlled drug delivery device. In this study, apomorphine was encapsulated as a model drug. Its therapeutic effect is limited due to its very short half-life and its strong emetic effect. Consequently, biodegradable microparticles would offer the advantage of improving therapeutic efficiency and compliance, by reducing administration frequency and minimizing systemic side effects. Apomorphine-loaded, PLA-co-PBED-based microparticles were prepared using an emulsion method. Microparticles based on PLGA 50:50 of different molecular weights were used as a reference. The obtained microparticles were characterized using various techniques. The residual content of dichloromethane (used as organic phase during microparticle preparation) was quantified and the in vitro release of apomorphine was studied. Interestingly, the functionalized polymers bearing free-carboxylic groups led to higher drug encapsulation efficiencies, lower residual contents of dichloromethane and different drug release patterns. These results suggest a promising application of these functionalized polymers to control drug release. Furthermore, the impact of the formulation parameters on the resulting physico-chemical properties of microparticles was studied. The main objective was to optimize the encapsulation efficiency, while minimizing initial burst release, to avoid toxic concentration peaks, and thus potential side effects. In this matter, some formulation parameters were varied during the preparation of microparticles based on PLGA 50:50 of 10 kDa. Optimal parameters were selected to achieve a zero-order apomorphine release over 10 days.On the other hand, it is well known that the in vitro drug release studies are crucial for the development of PLGA-based microparticles. However, as no standardized method has yet been established by authority agencies, very different methods are used in practice and their consequences on the resulting drug release kinetics are not well understood. Consequently, this work was intended to evaluate the impact of the experimental conditions on the resulting drug release kinetics from PLGA-based microparticles. Frequently applied setups were used. Different model drugs were encapsulated at different initial drug loadings. Various techniques were used to characterize the resulting formulations. Mathematical modeling was applied to better understand the observed phenomena. These results showed that the impact of the experimental conditions can be negligible or significant, depending on the type of formulation and the experimental setup. The observed differences could partially be explained by differences in the underlying drug release mechanisms. It can be concluded that great care must be taken when drawing conclusions from in vitro drug release measurements
Chabrol-Rivière, Sylvie. "La visite du délégué médical en cabinet de médecine générale a-t-elle une valeur formatrice ? : enquête auprès de 20 praticiens." Montpellier 1, 1992. http://www.theses.fr/1992MON11158.
Повний текст джерелаPeigné, Sophie. "Evaluation et comparaison de méthodologies pharmacocinétiques en pédiatrie." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCB146.
Повний текст джерелаNew legislation governing the development and authorization of medicines for use in children was introduced in the European Union (EU) in January 2007. This Regulation aims to facilitate the development and accessibility of medicinal products for use in the paediatric population, to ensure that medicinal products used to treat the paediatric population are subject to ethical research of high quality and are appropriately authorised for use in the paediatric population, and to improve the information available on the use of medicinal products in the various paediatric populations. Several rewards and incentives for the development of paediatric medicines for children are available in the European Union (EU). In compliance with the paediatric European regulation, a study will be conducted in paediatric patients with CHF with the objective to determine the efficacious and safe dose of ivabradine, a compound already marketed in adults, and to assess its efficacy and safety in children over 1 year old. A first work was to help design a paediatric study for ivabradine focusing on: the paediatric formulation evaluation, the doses to be administered, the sampling design and the sampling technique. A study was conducted in order to assess the relative bioavailability (Frel) of the paediatric formulation and a similar Frel was observed between the paediatric formulation and the adult marketed tablet. PBPK modelling was used to predict initial doses to be administered in the paediatric study and to select the most appropriate sample time collections. The dried blood spot (DBS) technique was recommended in the clinical trial in children. A secondary objective was to perform a comparison of the prediction of ivabradine pharmacokinetics (PK) in children using a physiologically-based pharmacokinetic (PBPK) approach and allometric scaling of a population pharmacokinetic (PPK) model. Simulations obtained by both the PBPK approach and allometric scaling of a PPK model were compared a posteriori to the paediatric study observations. Both PPK and PBPK approaches allowed an adequate prediction of the PK of ivabradine and its metabolite in children. The second work was done after the study conduction in the paediatric population. The study was performed in 116 children (74 received ivabradine, 42 received the placebo) aged from 6 months to less than 18 years old and data were analysed. The relationship between blood and plasma concentrations was described using linear mixed effect models. In order to describe ivabradine and its metabolite blood concentrations in children, a joint population PK model was developed taking into account weight & age effects on PK parameters. Plasma exposure comparison indicated that higher dose/kg were necessary to achieve a similar exposure between younger and older children. The PK/PD relationship in adult patients is conserved in children
Fahier, Julie. "Polymeric controlled release film coatings." Thesis, Lille 2, 2016. http://www.theses.fr/2016LIL2S025/document.
Повний текст джерелаPolymer coated pellets offer a great potential for control drug delivery system. Nevertheless, the underlying drug release mechanisms can be complex and are not fully understood. Thus, the impact of formulation parameters can be surprising. For example, it has been demonstrated during this thesis that:- The release of propranolol HCl was slower from sugar-based pellets coated with Kollicoat SR compared to microcrystalline cellulose (MCC)-based pellets.Generally, the opposite was observed because the sugar cores are osmotically active attracting more and more water into the system leading to a fast dissolution and diffusion of the drug, especially with high water-soluble drug. This unexpected result is due to a combination of two phenomena: (i) The plasticizing effect of sugar for the film coating and (ii) Decrease in drug solubility in the release medium due to the presence of co-dissolved sugar.In addition, Kollicoat SR 30 D [an aqueous dispersion of poly(vinyl acetate) also containing small amounts of poly(vinyl pyrrolidone) and sodium lauryl sulfate] is a very interesting polymer owing to its high flexibility and stable mechanical properties. However, sugar-based pellets tend to swell by the osmotic pressure created by the high water-soluble API and the sugar until crack formation, clearly visible on the images obtained by X-ray micro tomography.- Propranolol HCl release in phosphate buffer pH 7.4 increases by increasing the drug loading into the system, especially from MCC-based pellets.The opposite was often observed since the amount of water within the drug reservoir might not be sufficient to dissolve all drug. MCC-based pellets likely presented also cracks despite a low swelling of the system, accentuated by the increase of propranolol HCl concentration.To conclude, new insights on the underlying drug release mechanisms from Kollicoat SR coated pellets were provided. The importance of the type of drug and the nature of starter cores were elucidated.- In the second part, diprophylline loaded pellets coated with a polymer blend composed of Aquacoat ECD and Eudragit NM were prepared in order to control the drug release only by diffusion through the intact polymeric film and to predict the drug kinetics using mathematical models
Ferraro, Fabiana. "Enzyme-sensitive coatings for colon targeting : species-independent drug delivery systems." Electronic Thesis or Diss., Université de Lille (2022-....), 2023. http://www.theses.fr/2023ULILS035.
Повний текст джерелаThe aim of this thesis is to produce and characterize novel drug delivery systems for colon targeting.This project is part of the Interreg des 2 mers “Site-specific Drug Delivery” (https://www.interreg2seas.eu/fr/Site-Drug). The site-specific delivery of drugs to the colon presents major therapeutical advantages, for example in the treatment of inflammatory bowel diseases which required a local action. Conventional oral dosage forms lead to a fast and complete drug release in the stomach and small intestine and, generally, a systemic absorption into the bloodstream. Therefore, systemic concentrations of drugs and associated adverse effects can be considerable. Furthermore, the resulting concentrations of drug at the site of action (the inflamed colon) are low, resulting in low therapeutic efficacy. An ideal dosage form for the local treatment of colonic diseases should effectively prevent the release of the active substance in the stomach and small intestine. On the other hand, once the colon is reached, the release must begin and be controlled over time (including -if desired- a rapid and complete release). In the case of treatment of inflammatory diseases of the colon (e.g. Crohn's disease and haemorrhagic ulcerative colitis), the active ingredient is thus released at its site of action, offering optimal therapeutic effects and minimized side effects. Different types of drug delivery systems have been described in the literature aiming at site-specific release to the colon. Often, the drug is trapped in a polymeric matrix, or a drug reservoir (e.g. minigranules, capsules or tablets loaded with active ingredient) is coated with a polymeric film. The ideal polymers used for this purpose have low permeability for the drug in the upper part of the gastrointestinal tract, but become permeable as soon as the colon is reached. In order to allow such control delivery, various systems have been proposed, based in particular on: (i) changes in pH along the gastrointestinal tract, (ii) degradation of the polymer by enzymes preferentially located in the colon, or (iii) structural changes in the polymeric networks after a certain delay, such as the formation of cracks in low permeability films. Nevertheless, special attention should be paid because the pathophysiological conditions in the colon of patients with inflammatory bowel diseases may be significantly different from those in healthy subjects.(i) the pH of the contents of the gastrointestinal tract,(ii) the quality and quantity of microflora (secreting enzymes),(iii) transit times in different sections of the gastrointestinal tract. Thus, a galenic formulation which successfully releases an active ingredient in the colon of a healthy subject may fail in a patient. Similarly, the inter- and intra-individual variability of therapeutic effects can be considerable, if the dosage form is not appropriately adapted to the pathological state. The objective of this thesis project is to develop new galenic forms targeting the release of the active ingredient in the colon and which are adapted to the pathological state. The release of the drug will be triggered by enzymes located in the colon, regardless of the pathological state.1. Methods. The systems were prepared by functional coating of microgranules loaded with 5-ASA as drug. These systems have been characterized physico-chemically in different media simulating the gastrointestinal tract, this includes in particular exposure to media containing stools from patients with inflammatory bowel diseases as well as stools from animal models of these diseases (TNBS rats) and dog stools (healthy) under anaerobic conditions, in collaboration with INSERM U995 (Dr. Christel Neut). The main characterization technique used concerns the study of the release kinetics of systems exposed to these different release media [...]
Liu, Jun Hui. "Conception d'un système informatisé d'analyse rétrospective des prescriptions médicamenteuses." Paris 5, 2001. http://www.theses.fr/2001PA05CD02.
Повний текст джерелаFetouchi, Rachid. "Impact de la modulation de la signalisation calcique sur la réplication et l'expression protéïque du virus de l'hépatite C (VHC)." Paris 5, 2010. http://www.theses.fr/2010PA05T023.
Повний текст джерелаHepatitis C Virus (HCV) is a positive strand RNA virus affecting more than 170 million people in the world and responsible for chronic liver disease. We have previously shown that transient and stable expression of HCV Core protein decreases ER Calcium concentration and induces apoptotic cell death in a calcium dependent manner. We thus tested the hypothesis that modulation of calcium concentrations in the ER by specific drugs can have an impact on HCV protein expression and HCV replication. With the advent of the Huh7 cell line stably expressing the full length HCV genome (replicon system) and more recently systems to generate infectious virus particles in cell culture, we have the opportunity to check our initial hypothesis by modulating intracellular calcium concentrations with the following drugs: CAI, CsA, Debio-025, Thapsigargin, TbuBHQ and CGP37157. Intracellular calcium concentrations were assessed by specifically targeted recombinant aequorin calcium probes. Viral proteins expression was measured by Western Blot and Immunocytochemistry. The amount of viral RNA was evaluated by real-time quantitative RT-PCR. The ER is known to have a major role both in regulation of calcium signalling and in HCV proteins maturation and genome replication. Our results show that pharmacological modulation of intracellular calcium concentration affects HCV proteins expression and HCV replication. Our results are consistent with a pivotal role of calcium signalling in HCV replication and show a new class of drugs potentially able to control HCV infection
Amin, Alexandre. "La spectroscopie Raman appliquée au contrôle de qualité analytique libératoire et non-intrusif des préparations injectables cytotoxiques préparées à l'hôpital : évaluation et qualification opérationnelle." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS497.
Повний текст джерелаThe development of effective tools for the analytical quality control (AQC) of therapeutic objects (TO) appear to be a strong contributor to security of the cytotoxic drugs circuit in health care settings. Our goal is to ensure a high and stable quality in our pharmaceutical preparations for the benefit of patients and caregivers. Presently available analytical techniques have in common to be intrusive, destroying a fraction therapeutic solutions, exposing personal and generate specific toxic waste disposal. Compared to these, the non-intrusive analysis by Raman spectroscopy (RS) appears to us particularly innovative and has the capacity to significantly improve the specification of AQC technical specifications. The purpose of this work was to conduct an operational qualification of RS in the context of AQC. Special attention has been given to the feasibility of the new technical solution for SR, its impact on safety of persons and their working environment
Elgaied-Lamouchi, Dhouha. "Découverte de nouveaux excipients pharmaceutiques à base d'amidons modifiés pour une libération prolongée d'une substance active." Thesis, Lille, 2020. https://pepite-depot.univ-lille.fr/.
Повний текст джерелаHydrophilic matrix tablets are frequently used to control the drug release from oral dosage forms. Starch-based polymers are interesting matrix former in this respect, due to their biocompatibility, biodegradability, and availability from different plant sources. In addition to native starches, modified starches have been frequently used with various physiochemical modifications, which could be tailored to provide desired properties for a specific pharmaceutical application. Many scientists have reported the use of modified starches as matrix formers for oral controlled release tablets. Numerous starch-based extended release polymers have successfully retarded drug releases. However, most of the starch batches used in those studies are generally produced at a laboratory scale and may therefore present different properties compared to modified starches obtained with industrial scale. Hence, it could be very difficult to scale up the production of these excipients without changing their key features. The major goal of this work was to identify a new excipient, based on starch to control the drug release from direct compressible matrix tablets. Therefore, in a first instance, a large screening allowed to study different types of starches to prepare diprophylline matrix tablets. The effect of the botanical origin of starches, the type of pre-gelatinization method as well as of the degree and type of cross-linking and chemical substitution have been investigated, and the resulting drug release rates from diprophylline-loaded matrix tablets were measured. For a better understanding of these results, texture analysis of the gel-layer, created upon contact with the release medium, optical and scanning electron microscopy (SEM) as well as X- ray powder diffraction analysis were applied. Moreover, a “quick test” has been proposed to evaluate the potential of a particular type of starch to sustain the drug release rate. The obtained results on the importance of the starch type and their influence on the resulting drug release rates from matrix tablets can help for a better understanding and optimization of this type of advanced drug delivery systems. In a second phase, the potential of (PREGEFLO® PI10), has been evaluated as a matrix former for controlled release tablets. Hence, various types of matrix tablets loaded with drugs having different solubility were prepared by direct compression. The robustness of this cross-linked pregelatinized potato starch matrix was investigated in a variety of release media. In addition to that, several types of experimental USP apparatuses were used separately or combined with other devices to simulate the mechanical stress the tablets are exposed to during transpassage of the gastrointestinal tract. The obtained results showed that the drug release rates from PREGEFLO® PI10 matrix were not impacted by all the conditions studied. Therefore, the explored starch excipient offers an interesting potential as matrix former in controlled release tablets. Finally, to characterize the drug distribution throughout the matrix system, in particular in the “dry” and swollen tablet regions after hydration and the way the spatial distribution patterns change with time, the tablets were investigated using Raman imaging, SEM and Energy Dispersive X-ray Spectroscopy (EDX) before and after exposure to phosphate buffer. The Raman images confirmed that the drug is effectively trapped within the “dry” tablet core. The internal structure of the vacuum-dried tablets was visualized using SEM analysis. These observations highlighted the difference in the morphology between the “dry” core region and the region in which the tablet matrix underwent substantial swelling. The polysaccharide formed a continuous hydrogel in which the drug dissolved. SEM and EDX images have rendered visible the interface “dry “core-swollen gel and the spatial distribution of the drug in both regions. The diprophylline content is predictably much highe
Velghe, Carine. "Oral controlled drug delivery systems, optimization of release patterns and elucidation of release mechanisms." Thesis, Lille 2, 2013. http://www.theses.fr/2013LIL2S048/document.
Повний текст джерелаDevelopment of new galenic devices needs series experiments with variation of number parameters. For industrial, it’s a lost in time and money. Food and Drug Administration initiated since several years, Process Analytical Technology (PAT) as a tool to analyze and control pharmaceutical process. These tools can be helpful to determine drug release mechanism and allow application of mathematical model to predict drug release kinetics. One objective of this work is to develop a mechanistically realistic mathematical model allowing for the quantification of vitamin release from Compritol 888 (glyceryl dibehenate NF)-based matrix tablets, prepared either by direct compression or via hot-melt extrusion/grinding/compression. Nicotinic acid has been used as highly soluble drug in surrounding medium. Dissolution studies show vitamin release rates increased with increasing initial niacin content, due to the increased matrix porosity upon vitamin depletion. In all cases, niacin release from tablets prepared via hot-melt extrusion was slower than from tablets prepared by direct compression, due to more intense embedding of the vitamin within the lipid. Importantly, a numerical model based on Fick’s law of diffusion and considering the co-existence of dissolved and non-dissolved vitamin could successfully be used to quantify vitamin release from both types of tablets, irrespective of the initial niacin loading and tablet size. In-silico simulations can be very helpful to accelerate product optimization of Compritol 888-based matrices, saving development time and costs. For multiparticulates systems, and more again for coated forms, mathematical models are more complexes. In this goal, development of new tools to characterize devices is primordial. Technology Terahertz offers an interesting potential. This technique can be used to detect difference in size and uniformity for polymeric film from multilayer pellets of 1 mm diameter. Pellets consisting of a sugar starter core and a metoprolol succinate layer were coated with a Kollicoat® SR: Kollicoat® IR polymer blend. Pellets with several coating thickness are studied. No drug layer thickness difference between batches was observed, and the average coating thicknesses were 46 µm, 71 µm and 114 µm, for the different batches. Terahertz results compared with experimental data from dissolution methods, allow predicting coating thickness results correlated with the subsequent drug release behavior. Multiparticulates systems have important interest: they allow avoiding “dose dumping”. Dose dumping is described as an unintended, rapid drug release in a short period of time of the entire amount or a significant fraction of the drug contained in a modified release dosage form (Meyer, 2005). This phenomenon can be observed in the case of ethylcellulose-based devices in presence with ethanol rich-media. Recently, ethylcellulose:guar gum blend have been reported to provide ethanol-resistant drug release kinetics from coated dosage forms. Theophylline matrix pellets were coated with ethylcellulose: guar gum blends. These granules show no change in drug release profiles upon contact with medium containing 40% of ethanol (v/v). This is because the ethanol insoluble guar gum effectively avoids undesired ethylcellulose dissolution in ethanol-rich bulk fluids. However, so far the importance of crucial formulation parameters, including the minimum amount of guar gum to be incorporated and the minimum required guar gum viscosity, remains unclear. It was found that more than 5% guar gum (referred to the total polymer content) must be incorporated in the film coating and that the apparent viscosity of a 1% aqueous guar gum solution must be greater than 150 cPs to provide ethanol-resistance. [...]
Strich, Samuel. "Oral drug delivery systems based on polysaccharides for colon targeting." Electronic Thesis or Diss., Université de Lille (2022-....), 2023. http://www.theses.fr/2023ULILS081.
Повний текст джерела10 million people worldwide, over 1.5 million in North America and 2 million in Europe. Those are the numbers of people affected by inflammatory bowel disease (IBD) in each region quoted, respectively. Including both Crohn's disease (CD) and ulcerative colitis (UC), inflammatory bowel disease has emerged as a public health challenge worldwide in the past decades. Often diagnosed between 15 and 35 years old, IBD are characterized by moderate to severe symptoms, and have in common relapsing-remitting cycles of mucosal inflammation.To date, there is no cure for IBD. Defined as colon targeting, targeted drug delivery systems is a way to get selective and efficient delivery of pharmacologically active compounds to the predetermined targeted region in therapeutic concentrations along with minimizing side effects of the drug. Current strategies for colon targeting rely on : *) prodrugs, **) pH-dependant systems, ***) time-dependant systems, ****) microbially triggered systems.Of all approaches, microbiota sensitive systems are currently known as the best ones for colonic drug delivery. It is also possible to combine several complementary approaches (pH- and microbiota sensitive) to significantely favor localized drug release.Our project aimed to develop 5 mm mini-tablets for colon targeting. First, a comparison of different film coatings was made to highlight the most interesting drug release profiles. Then, an innovative formulation, combining synthetic and natural polymers as well as polysaccharides, was evaluated. Different blend ratios were selected as well for films as for coated mini-tablets. In vitro drug release was carried out in simulated digestive fluids for a 32 h duration, including:- 0.1 N HCl or simulated gastric fluid (2 h)- PBS 6.8 or simulated intestinal fluid (6 h)- Colonic simulated medium with and without patients' faeces (24 h).Colonic simulated medium inoculated with patients' faeces allowed for working closer to pathophysiological conditions. Relevant results were obtained and paved the way for a promising monolayer technology. None or negligible drug release occurred up to 8 h, in the upper GIT. Also, drug could be totally protected in the lower gastrointestinal tract.Ethylcellulose, as a thermoplastic polymer, prevented from premature dissolution.Shellac, as a natural resin, provided pH-dependant properties.The adjunction of a polysaccharide acted as a substrate of microbiota.Interestingly, colonic release profiles could be optimized depending on the amount of polysaccharide added into the system
Benzine, Youcef. "Enzymatically triggered polymeric drug delivery systems for colon targeting." Thesis, Lille 2, 2019. http://www.theses.fr/2019LIL2S036.
Повний текст джерелаChronic inflammatory bowel diseases (IBD) today affects close to 200,000 people in France. They are characterized by the inflammation of the wall of a part of the digestive tract. They usually include Ulcerative Colitis and Crohn’s disease. Both are chronic diseases that involve inflammation of the colonic mucosa. The main difference between Crohn’s disease and Ulcerative Colitis is the location and nature of inflammation. Crohn’s disease can affect any part of the GIT from mouth to anus but in most cases attacks the terminal ileum. In contrast, Ulcerative Colitis is restricted to the colon and the rectum. An ideal dosage form should effectively protect the drug in the stomach and small intestine and subsequently release the drug in the colon in a targeted and controlled manner. The objective of this work was to develop new drug delivery systems containing a polysaccharide (pectin, guar gum, inulin ...), which are degradable by the colonic bacteria and a hydrophobic thermoplastic polymer (ethylcellulose, polyurethane, polyvinyl acetate ...), which will reduce the hydrophilicity of the polysaccharide. The technique used for the preparation of these dosage forms is hot-melt extrusion. It is a continuous and free solvent process that allows the manufacturing of a dosage form called "extrudate" by forcing the soften material through an orifice. It has been demonstrated that extrudates based on polyvinyl acetate/polyurethane and inulin can minimize the release of a model active substance in the upper part of GIT due to the hydrophobic properties of polyvinyl acetate. Indeed, these extrudates uptake low amount of water and lose low dry mass upon exposure to media simulating the stomach and the small intestine. However, once in contact with the colonic flora, these systems show a considerable loss of mass due to the degradation of inulin by enzymes secreted by colonic bacteria. In another study, hot melt extrudates based on ethylcellulose blended with different types of polysaccharides (guar gum, inulin, corn starch, maltodextrin, pectin and chitosan) were studied for the development of controlled drug delivery systems. Anhydrous theophylline and diprophylline have been used as model drugs. This study was useful to set the extrusion parameters: temperature 100 °C; screw speed 30 rpm; feed rate 3 cc/min; 30 % dibutyl sebacate as a plasticizer. Importantly, hot melt extrudates based on ethylcellulose:guar gum blends offer an interesting potential as controlled drug delivery systems: They can be prepared at temperatures of about 100 °C, provide broad spectra of drug release patterns (in particular about constant drug release rates). Finally, hot melt extrudates remained stable after 1 year storage at ambient conditions
Chazard, Emmanuel. "Automated detection of adverse drug events by data mining of electronic health records." Phd thesis, Université du Droit et de la Santé - Lille II, 2011. http://tel.archives-ouvertes.fr/tel-00637254.
Повний текст джерелаCantin, Oriane. "PEO hot melt extrudates for controlled drug delivery." Thesis, Lille 2, 2016. http://www.theses.fr/2016LIL2S035/document.
Повний текст джерелаAmong continuous manufacturing processes, hot melt extrusion is a technique with growing interest in the pharmaceutical field. This process enables the formation of solid dispersions of many drugs within a polymeric or lipidic carrier. Hot melt extrusion can be widely used for different issues using the appropriate carrier and drug. Here are the mostly used concepts in pharmaceutical solid dosage forms: (i) immediate release, (ii) modified release and (iii) taste masking. Modified release systems have been taken into account to be very interesting devices for the improvement of drug- bioavailability, drug- efficacy as well as the patient compliance. Various systems with different release mechanisms can be manufactured, depending on the nature of the carrier (inert, erodible, and swelling matrices). Poly ethylene oxide is a semi crystalline and hydrophilic polymer which can be used to control drug delivery. The poly ethylene oxide melting point ranging from 63 to 67 °C makes it suitable for hot melt extrusion. Importantly, the swelling capacities of the hydrophilic poly ethylene oxide matrices are able to deliver drug in a time controlled manner, in respect of the poly ethylene oxide molecular weights. The purposes of this work were (i) to study the impact of critical process parameters (extrusion temperature and screw speed) on the drug release behavior, (ii) to determine the impact of formulation parameters (poly ethylene oxide molecular weight, nature of drug and drug loading) on drug release kinetics, and (iii) to evaluate solid dosage forms prepared by hot melt extrusion versus direct compression. Interestingly, the variation of the extrusion temperature and the screw speed leads to the altering of the extrudate appearance and thus the distribution of drug into the extrudate. However, this changing has not influenced the drug release remarkably. Thus, this study was useful to set the parameters for the following projects (temperature 100 °C; screw speed 30 rpm; dosage form size 1 cm). Poly ethylene oxide hot melt extrudates containing 10 % theophylline and based on 100 - 7,000 kDa poly ethylene oxide are used for this thesis. Importantly, the drug release decreased substantially with the increase of the poly ethylene oxide molecular weight from 100 to 600 kDa. However, further increasing of the molecular weights leads to only a slight decrease in the release rate. Swelling studies have shown that this phenomenon correlated with the change in volume of the opaque part of the extrudates (non-transparent gel and solid core)
Ponchel, Amélie. "Fatigue post-accident vasculaire cérébral : facteurs associés et impact des troubles cognitifs et émotionnels." Thesis, Lille 2, 2016. http://www.theses.fr/2016LIL2S049/document.
Повний текст джерелаPost-stroke fatigue (PSF) is frequent and debilitating. However, PSF is up to date a poorly understood and unrecognized phenomenon. In this thesis, we have done an exhaustive synthesis of scientific literature on factors associated with PSF. It indicates that PSF is frequently related with depressive and anxious symptoms but there is a lack of understanding of its physiopathological mechanisms. We conducted a study of PSF on 153 patients from the hospital-based cohort study STROKDEM (NCT01330160), followed-up for 6 months after an ischemic stroke. In a first study, we have shown that PSF was not a side effect of drugs use. PSF more reflects presence of disturbances frequently observed after stroke such as depression, anxiety, or sleep disturbances. In a second study, we have observed a strong association between PSF and subjective cognitive complaints that contrasted with the absence of association with objective cognitive performances during the neuropsychological evaluation, regardless of the considered cognitive domain. In a third study, we explored neuronal mechanisms underlying PSF. With an exploratory analysis, without a priori, we did not demonstrate any difference in functional connectivity at rest between patients with or without PSF. As a whole, these data give us pieces to progress in the understanding of the complex phenomenon named PSF
Vaugelade, Cécile. "Façonnage de nouveaux matériaux biorésorbables à hydrophilie variable. Synthèse et caractérisation de poly(glyoxylate de méthyle -co- glyoxylate de potassium)." Rouen, 1999. http://www.theses.fr/1999ROUES066.
Повний текст джерела