Formes galéniques innovantes sensibles aux bactéries pour le ciblage du colon

Chronic 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.De nos jours, les maladies inflammatoires chroniques de l'intestin (MICI) comme la rectocolite hémorragique et la maladie de Crohn touchent près de 200 000 personnes en France. Elles se caractérisent par l'inflammation de la paroi de différentes régions du tractus gastro-intestinal (TGI). Les deux sont des maladies chroniques qui impliquent une inflammation de la muqueuse colique. La principale différence entre la maladie de Crohn et la rectocolite hémorragique réside dans la localisation et la nature de l’inflammation. La maladie de Crohn peut toucher n’importe quelle partie du tractus gastro-intestinal (TGI), de la bouche à l’anus, mais dans la plupart des cas, elle atteint l’iléon. En revanche, la rectocolite hémorragique est limitée au côlon et au rectum.Le ciblage du colon peut offrir des avantages majeurs pour le traitement des MICI. Les formes galéniques conventionnelles entraînent une libération prématurée de la substance active dans l'estomac et l’intestin grêle. La substance active est alors absorbée dans la circulation sanguine ce qui provoque de sérieux effets secondaires. De ce fait la concentration de substance active qui arrive au site d’action (partie distale du TGI) est très faible, ce qui entraîne une faible efficacité thérapeutique voire échec de la thérapie.Pour pallier ce problème, une forme galénique idéale devrait effectivement protéger la substance active dans le haut TGI, puis la libérer dans la partie distale du TGI de manière contrôlée. Des systèmes réservoirs (granules enrobés, capsules…) ou des systèmes matriciels (comprimés, extrudats…) peuvent être utilisés pour protéger la substance active dans le haut TGI. Les polysaccharides qui ne sont dégradés que par des enzymes bactériennes localisées dans le colon peuvent être utilisés dans le développement des formes galéniques pour le traitement des MICI. L’objectif de ce travail était de développer de nouvelles formes galéniques contenant un polysaccharide (pectine, gomme de guar…) dégradable par la flore colique et d’un polymère thermoplastique hydrophobe (éthylcellulose, HPMC…) qui vas réduire l’hydrophilicité du polysaccharide. Or, le mélange des deux polymères ne doit pas enrober le polysaccharide qui va servir pour le ciblage de la partie distale du TGI

الحكومة الإلكترونية في الجزائر-دراسة مقارنة بدول شمال إفريقيا = E-government in Algeria - a comparative study with North African countries

: استهدفت هذه الورقة البحثية عرض تجربة الجزائر في مجال الحكومة الإلكترونية ومقارنتها بدول شمال إفريقيا، وتحديدا تونس والمغرب ومصر بهدف تقييم وضعها على المستوى الإقليمي، وتمت المقارنة استنادا إلى مؤشر نضج الحكومة الإلكترونية الصادر عن الأمم المتحدة، والذي يشمل كل من المؤشر الفرعي للبنية التحتية ، والمؤشر الفرعي للرأسمال البشري ، والمؤشر الفرعي للخدمة الحكومية الإلكترونية في الفترة الممتدة بين 2008 و2020. وهذا بهدف الاستفادة من هذه الدول في تجربتها للحكومة الإلكترونية، واستغلال الفرص المتاحة أمام الجزائر لتطوير حكومتها الإلكترونية، ومواكبة الحركة العالمية، والرفع من كفايتها بما يخدم أهداف التنمية المستدامة؛ خاصة أن الحكومة الإلكترونية ما تزال في الجيل الأول، وأمامها العديد من التحسينات. . E-government in Algeria -A comparative study of North African countries This research paper aims to present Algeria’s experience in the field of e-government and compare it with North African countries, Tunisia, Morocco and Egypt, in order to assess its situation at the regional level. The comparison was made based on the e-government development index (EGDI) issued by the United Nations, which includes the infrastructure sub-index (TII), human capital sub-index (HCI) and e-government service sub-index (OSI), in the period between 2008 and 2020. the aim of this comparison is taking advantage from the experiences of these countries and learning lessons to face the challenges, and use the opportunities available to Algeria to develop its e-government, and to keep pace with the global movement and to increase its efficiency to serve the goals of sustainable development. Key words: E-Government, E-Government Development Index, Algeria, Egypt, Tunisia, Morocco

Systèmes d'administration de médicaments sensibles au microbiote basés sur des polysaccharides naturels pour le ciblage du côlon

International audienceColon targeting is an ongoing challenge, particularly for the oral administration of biological drugs or local treatment of inflammatory bowel disease (IBD). In both cases, drugs are known to be sensitive to the harsh conditions of the upper gastrointestinal tract (GIT) and, thus, must be protected. Here, we provide an overview of recently developed colonic site-specific drug delivery systems based on microbiota sensitivity of natural polysaccharides. Polysaccharides act as a substrate for enzymes secreted by the microbiota located in the distal part of GIT. The dosage form is adapted to the pathophysiology of the patient and, thus, a combination of bacteria-sensitive and time-controlled release or pH-dependent systems can be used for delivery

When drugs plasticize film coatings: Unusual formulation effects observed with metoprolol and Eudragit RS

International audienceMetoprolol tartrate and metoprolol free base loaded pellet starter cores were coated with Eudragit RS, plasticized with 25% triethyl citrate (TEC). The initial drug loading and coating level were varied from 10 to 40 and 0 to 20%, respectively. Drug release was measured in 0.1 N HCl and phosphate buffer pH 7.4. The water uptake and swelling kinetics, mechanical properties and TEC leaching of/from coated pellets and/or thin, free films of identical composition as the film coatings were monitored. The following unusual tendencies were observed: (i) the relative drug release rate from coated pellets increased with increasing initial drug content, and (ii) drug release from pellets was much faster for metoprolol free base compared to metoprolol tartrate, despite its much lower solubility (factor >70). These phenomena could be explained by plasticizing effects of the drug for the polymeric film coatings. In particular: 1) Metoprolol free base is a much more potent plasticizer for Eudragit RS than the tartrate, leading to higher film permeability and overcompensating the pronounced differences in drug solubility. Also, Raman imaging revealed that substantial amounts of the free base migrated into the film coatings, whereas this was not the case for the tartrate. 2) The plasticizing effects of the drug for the film coating overcompensated potential increasing limited solubility effects when increasing the initial drug loading from 10 to 40%. In summary, this study clearly demonstrates how important the plasticization of polymeric controlled release film coatings by drugs can be, leading to unexpected formulation effects

Injection-molded capsule bodies and caps based on polymer blends for controlled drug delivery

International audienceA variety of polymer:polymer blends was used to prepare hot melt extrudates and empty capsules (bodies and caps) by injection-molding using a benchtop extruder (Babyplast). Kollidon SR:inulin and Carbothane:inulin blends were investigated. The impact of the blend ratio on the water uptake and dry mass loss kinetics upon exposure to 0.1 M HCl, phosphate buffer pH 6.8 and culture medium optionally inoculated with fecal samples from Inflammatory Bowel Disease (IBD) patients were studied. Hot melt extrudates were loaded with up to 60 % theophylline, capsules were filled with drug powder. Increasing the inulin content led to increased water uptake and dry mass loss rates, resulting in accelerated drug release from the dosage forms, irrespective of the type of polymer blend. This can be attributed to the higher hydrophilicity/water-solubility of this polymer compared to Kollidon SR and Carbothane. Interestingly, the presence of fecal samples in culture medium increased the water uptake and dry mass loss of hot melt extrudates to a certain extent, suggesting partial system degradation by bacterial enzymes. However, these phenomena did not translate into any noteworthy impact of the presence of colonic bacteria on theophylline release from the investigated extrudates or capsules. Hence, drug release can be expected to be independent of the location “small intestine vs. colon” from these dosage forms, which can be advantageous for long term release throughout the entire gastro intestinal tract

Hot melt extruded polysaccharide blends for controlled drug delivery

International audienceDifferent types of hot melt extrudates were prepared based on a variety of blends of ethylcellulose with a 2nd polysaccharide, namely hydroxypropyl methylcellulose (HPMC), pectin, maize starch, inulin, maltodextrin, guar gum, and chitosan. In selected cases, the polymer:polymer blend ratio was varied from 80:20, 70:30, 60:40, 50:50, 40:60, 30:70 to 20:80. The addition of appropriate amounts of plasticizers allowed reducing the extrusion temperature to about 100 °C. The impacts of the screw speed, extrusion temperature, amount and type of plasticizer as well as of the amount and type of drug (10–60% theophylline or diprophylline) were studied. Drug release was measured in 0.1 M HCl for 2 h, followed by phosphate buffer pH 6.8 and (optionally) fecal samples to simulate the colon (under anaerobic conditions). DSC measurements and optical microscopy were used to characterize the physical state and morphology of the systems. Interestingly, hot melt extrudates based on ethylcellulose:guar gum blends could be easily prepared at a temperature of 100 °C and offered large spectra of drug release patterns for both: slightly water-soluble theophylline as well as freely water-soluble diprophylline. About constant drug release rates could be obtained during prolonged periods of time. Importantly, the resulting drug release rates from hot melt extrudates based on ethylcellulose:guar gum 80:20 blends were similar in the presence and absence of colonic bacteria, indicating that the ethylcellulose seems to protect the guar gum from degradation upon exposure to fecal samples. Furthermore, these systems were long term stable for at least 1 year under ambient conditions. Thus, they can offer an interesting potential as oral controlled drug delivery systems

Ciprofloxacin loaded vascular prostheses functionalized with poly-methylbeta- cyclodextrin: The importance of in vitro release conditions

Synthetic Vascular Graft Infection (SVGI) can be very serious for patients with dramatic consequences (up to 6%). Polyester vascular grafts (PET) were modified with polymerized cyclodextrin (Poly-MeβCD) and loaded with ciprofloxacin (CFX) for the prevention of postoperative infections. The aim of this study was to investigate the CFX/Poly-MeβCD interactions and the importance of the type of the dissolution technique. The solubility of CFX was significantly improved upon Poly-MeβCD, and the interaction between CFX and Poly-MeβCD were observed by NMR (Nuclear Magnetic Resonance). Drug release was measured in phosphate buffer saline pH 7.4 at 37 °C using: (i) agitated flasks, (ii) the paddle apparatus, (iii) the conventional flow-through cells, (iv) the modified flow-through cells with agarose gel at different flow rates. Importantly, CFX release depends on the flow rate as well as the experimental set-up in vitro. CFX release from virgin prostheses (PET) was faster than from functionalized prostheses (PET-MeβCD), irrespective of the flow rate, which indicates the superiority of Poly-MeβCD in the control of CFX release. The CFX diffusion from PET-MeβCD into agarose gel showed a continuously progressive diffusion during 7 days. Thus, this test can be highly appropriate for in vitro characterization of such drug delivery systems