Since 1998, the French Health Insurance (NHI) system had established a national database in order to reimburse drug prescriptions. These electronical data are a considerable potential source for syndromic surveillance because of their exhaustive and regular updates. The aim of this study was to develop a method to identify acute gastroenteritis (AG) cases from drug reimbursements of the NHI database. The algorithm aimed at discriminating AG from other pathologies was determined from a sample of 206 AG prescriptions and 351 non-AG prescriptions collected in five pharmacies. The AG case identification was mainly based on the lag time between the prescription and delivery day, the occurrence of non-AG case-specific drugs, AG case-specific drug associations and treatment duration. The discriminant algorithm led to a sensitive and specific indicator of medically treated cases of AG with a time-spatial resolution power which met the need for waterborne AG surveillance.
The inclusion behavior of natural cyclodextrins (CDs) and polymers based on natural cyclodextrins (CD-polymer), in solution and in solid-state, was studied towards a poorly water-soluble anti-helminthic drug, albendazole (ABZ), chemically methyl[5-(propylthio)-1-H-benzimidazol-2yl]carbamate. Drug-cyclodextrin solid systems were prepared by freeze-drying. Phase solubility study was used to evaluate the interaction in solution, between ABZ/(CDs) and ABZ/CD-polymers. The stability constants of ABZ/natural CDs and ABZ/CD-polymers complexes were calculated by phase solubility method. The apparent solubility of Albendazole was enhanced especially with poly alpha-CD. The formation of inclusion complexes with natural CDs and polymers of cyclodextrin in the solid-state form were confirmed by Fourier Fransform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC) and proton Nuclear Magnetic Resonance Spectroscopy (1H-NMR).
Oral drug delivery remains the most physiological and therefore the most preferred, simplest and easiest administration route. Nevertheless, a multitude of potentially clinically important drugs will not reach the market or achieve their full potential unless their oral bioavailability is improved by formulation. The aim of this review is to present an overview of properties, formulation, excipients and characterization of solid dispersions corresponding to one of the different formulation strategies for design and development of poorly soluble drugs. This work will review and compare in detail the evolution of solid dispersions focused on the different methods of formulation and production of solid dispersions, their stability, their release properties, their pharmacokinetics and methods for their physicochemical characterization.
Cryptosporidiosis, the leading cause of endemic and epidemic diarrhoeal disease worldwide is due to Cryptosporidium parvum, a spore-forming protozoan. Anticryptosporidial pharmacological and/or immunological agents were initially tested in immunodeficient models of cryptosporidiosis, and sinefungin exhibited a significant dose dependent curative and preventive activity. Shedding relapses observed after discontinuation of sinefungin therapy lead to identify the bile ducts as a protected reservoir that may sustain chronic infection. The MIC50 of the sinefungin observed in vitro studies is 14.5 microg/ml. It is a hydrophilic drug lowly absorbed when orally administered and nephrotoxic after IV injection. To avoid this toxic effect, Neal's team prepared sinefungin loaded microspheres and proved that encapsulated sinefungin was 10 times more effective than free sinefungin. This optimistic result led us to study the nanoparticles as drug carrier for sinefungin. In this study, we prepared optimal sinefungin loaded PLGA nanoparticles. Physico-chemical characterization, in vitro drug release and in vivo studies were assessed. Negative surface-charged (-56.1 mV) sinefungin loaded PLGA nanoparticles were prepared with a homogenous size of 200 nm. Optimal formulation led to a drug content of 9.18% w/w (4.59 mg) and a drug entrapment of 15.16%. Dilution technique was used to study the release of sinefungin in vitro. 93.03% of sinefungin were released from dilution 1:5 to 1:20. This burst effect could probably due to the adsorption of the drug on the surface of the nanoparticles. A second step with a lower release was observed from dilution 1:20 to 1:100 which may correspond to the diffusion out of the drug solution from the nanoparticles into the bulk release medium. Investigations in rats showed that only 1.23 mg of sinefungin loaded in PLGA nanoparticles led to a decrease of sinefungin in the urine (0.23 mg vs. 4.27 mg for IV administration of free sinefungin) and to an increase of sinefungin concentration in the bile (6.63 microg/ml vs. 3.89 microg/ml for IV administration of free sinefungin). But the biliary concentration of encapsulated sinefungin (6.63 microg/ml) is still nearly 2 times lower than the MIC50.
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