Biomedical subjects

Dominique Pradeau

Publications and source records attributed to Dominique Pradeau.

6 recordsLinked to original sources

PubMed2006

Evaluation of critical formulation parameters influencing the bioactivity of beta-lactamases entrapped in pectin beads.

The bioactivity of beta-lactamases upon entrapment in calcium-pectinate beads was evaluated. Non-amidated (NAP) and amidated pectin (AP) beads were prepared according to the ionotropic gelation method using calcium chloride (CaCl(2)) as gelling agent, washed and dried at 37 degrees C in an oven for 2h. Both enzyme activity and protein content were determined as well as bead calcium content. NAP allowed a better encapsulation of the protein than AP. Increasing both CaCl(2) concentration and bead residence time in the gelation medium led to a significant loss of beta-lactamase activity. The drying process of beads also lowered the enzyme activity. Moreover, bead calcium content increased as the CaCl(2) concentration augmented. Being very hygroscopic, the excess of CaCl(2) correlates with an increase of moisture content in beads that affects enzyme activity. After elimination of free calcium from beads, it was shown that a small amount is needed to form the Ca-pectinate network and that the activity of beta-lactamases is preserved in these conditions. Therefore, the bioactivity of encapsulated beta-lactamases in pectin beads mainly depends on formulation parameters such as pectin type, CaCl(2) concentration, washing and drying processes.

Calcium↗

PubMed2003

Aluminum contamination of parenteral nutrition and aluminum loading in children on long-term parenteral nutrition.

BACKGROUND: Children who are receiving parenteral nutrition are at risk of aluminum overload, which may contribute to such side effects as osteopenic bone disease. The aim of the present study is to determine the aluminum contamination of parenteral nutrition solutions and their components, and to assess the aluminum status of children on long-term parenteral nutrition. METHODS: Aluminum concentrations were determined by graphite furnace absorption spectroscopy in components and in final parenteral nutrition solutions. The urinary aluminum excretion and plasma aluminum concentration were determined in 10 children on long-term parenteral nutrition. RESULTS: The mean aluminum concentration in the administered parenteral nutrition solutions was 1.6 +/- 0.9 micromol x l(-1)(mean +/- standard deviation (SD)). The resulting mean aluminum daily intake of the 10 patients was 0.08 +/- 0.03 micromol x kg(-1) x day(-1). CONCLUSIONS: Compared to two previous studies performed in 1990 and in 1995 in our hospital, the aluminum contamination of parenteral nutrition solutions and the daily aluminum intake of the children seemed to decrease. However, the plasma aluminum concentration and daily urinary aluminum excretion of the children still remain above normal standards. The children had no clinical symptoms of bone disease but aluminum accumulation in tissue can not be excluded. To prevent this iatrogenic toxicity, the aluminum contamination of parenteral nutrition should be assessed regularly.

Adolescent↗

PubMed2003

[Infusion solutions].

Infusion solutions or preparations for intravenous administration have been developed since 1830 after the work of Thomas Latta. This particular pharmaceutical form, which brings large accounts of liquid (100 to 3000 ml) and nourishes, equilibrates, hydrates, clears, serves as a vehicule for many drugs and allows organ storage, has had a considerable development owing to its successes in a number of severe diseases and because it has supported the emergence of critical care and intensive care medicine. This form has an unappreciated story. It was first used in hospitals but it is now manufactured by the pharmaceutical industry after a long series of technical improvements and galenic innovations bringing solutions to the problems successively encountered (microbial contamination, embolism, blood alteration, "saline fever", degradation and adsorption of drugs, allergic shock...) and answers to the new requirements resulting from progresses in physiology and biology (hydroeletrolytic support, plasma expansion, energy supply, acidobasic homeostasis, malnutrition...). This story is depicted with respect to the indications, the formulation, the infusion devices from the origin to nowadays.

History, 19th Century↗

PubMed2002

Adsorption of an ionizable drug onto microspheres: experimental and modeling studies.

The purpose of this work was to study the in vitro equilibria and the adsorption kinetics of an ionizable drug, indomethacin, onto commercially available cationic polymeric microspheres: DEAE Trisacryl LS and QA Trisacryl LS. Isotherms were fitted to theoretical equations allowing accurate predictions of drug loading at different salt concentrations. Isotherm measurements were quickly obtained by simple column breakthrough experiments. The nature of the ion exchange group of the microspheres was observed to be preponderant for adsorption, as the tertiary amine derivative exhibited 53% more capacity than its quaternary amine counterpart. The maximum equilibrium uptake capacity in a 5 mM Tris-HCl buffer at pH 7.4 is 303 mmol/ml of particle volume, for DEAE microspheres. Transport properties of indomethacin into the tertiary amine microspheres were obtained in agitated contactor. Microbeads loading was completed in a 1-6 min range and was found to be controlled by pore diffusion mechanism. Equilibrium uptake data was fitted to the Langmuir and the mass action law models. Adsorption kinetics were fitted to a pore diffusion model. Good correlation was obtained between the theoretical models and the experimental data. The methodology outlined in this work provided a simple approach of estimating adsorption behavior of drugs onto ion-exchange macroporous microspheres. Although significant indomethacin loading was obtained onto the DEAE microspheres, the rapid rate of diffusion is not compatible with sustained release properties sought for this type of microspheres.

Adsorption↗

PubMedDate not supplied

Topical treatment of experimental hydrofluoric acid skin burns by 2.5% calcium gluconate.

Topical therapy with 2.5% calcium gluconate gel is considered as the "first-aid" treatment of accidental hydrofluoric acid skin burns. The efficacy of three different gel formulations varying in the amount and/or nature of their gelling and moisturizing agents was experimentally evaluated. Thirty male Wistar-Han rats (250 g) were exposed to 60 mul of 40% hydrofluoric acid for 2 minutes on two spots (4 cm) of skin under pentobarbital anesthesia. One lesion was massaged with 1 g of gel (10 rats/type of gel) at 3 minutes; 30 minutes; 1 hour; 1 hour, 30 minutes; 2 hours; 3 hours; and 4 hours after injury. During the next 3 days, rats received a single daily application of gel. The other lesion for each rat remained untreated (control). From day 1 after injury to the end of the study (day 17), gel therapy reduced the number of extensive (-66%), severe (-44%), and moderate (-34%) lesions (P < .0001). It reduced (P < .001) the median Area Under the Curve day 0-17 of burn injury from 34.0 (25th to 75th percentile: 18.2-44.5; untreated lesions) to 17.7 (7.0-26.7); overall, there was three cases of treatment failure. At day 17, full wound recovery was obtained in 14 cases by gel therapy compared with 6 in the absence of treatment. The efficacy of the three gel formulations was comparable for all evaluated parameters. Repeated applications of a 2.5% calcium gluconate gel is an efficient treatment of experimental 40% hydrofluoric acid skin burn; few differences were observed between evaluated gel formulations.

Administration, Topical↗

PubMedDate not supplied

Evaluation of peracetic acid permeation during flash sterilization through pharmaceutical plastic polymers used in cytotoxic reconstitution units.

Peracetic acid (PAA) permeation in flash sterilization was studied using three different plastic infusion bags made of polypropylene and polyethylene, filled with glucose 5% or NaCl 0.9%. The pH was measured and acetic acid (AA) and PAA concentrations were made by reverse phase high-performance liquid chromatography (RP-HPLC). PAA was derivatized by oxidation of methyl tolyl sulfide (MTS) into methyl tolyl sulfoxide (MTSO) detected by ultraviolet (UV) absorbance at 230 nm. The technique has a sensitivity of 0.3 microg x L(-1) and was highly specific. Results showed that pH measurements remain constant and demonstrated the absence of PAA permeation, which was confirmed by the absence of AA permeation regardless of the brand tested, with both unwrapped and overwrapped infusion bags, when flash sterilization is applied. These results allow flash sterilization to be performed with unwrapped infusion bags without any risk of drug degradation by PAA. This makes compounding safer and easier, which improves productivity.

Antineoplastic Agents↗