Biomedical subjects

J C Chaumeil

Publications and source records attributed to J C Chaumeil.

At least 19 recordsLinked to original sources

PubMed2006

Development of a thermogelling ophthalmic formulation of cysteine.

Preliminary studies carried out with cysteine 2% solution showed that pH adjusted to isoelectrical pH (i.e., 4.9) led to enhance stability during autoclaving and ensured no significant degradation during at least 14 days if stored at 2-8 degrees C protected from light. Optimized formulations combined either cysteine(2%)/Poloxamer407(16.5%) or cysteine(2%)/Poloxamer407(20%)/Poloxamer188(5%) and were characterized by an adequate temperature of gelification (TG) (25.9 degrees C and 26.9 degrees C, respectively), an important gel strength (5.1daN and 5.3daN, respectively) and a drastic increase in the apparent viscosity between 24 degrees C and 32 degrees C (multiplication factor of 78 and 77-fold, respectively). Cysteine addition produced only slight but significant decrease in temperature of gelification and increase in gel strength.

Chemistry, Pharmaceutical↗

PubMed2005

Release of a macromolecular drug from alginate-impregnated microspheres.

Macroporous microspheres were impregnated with calcium alginate to encapsulate fluorescein isothiocyanate-labeled dextran (FITC-dextran) and control its release. The detailed study of the impregnation process lead to its optimization: the quantity of alginate in the impregnated microspheres and the FITC-dextran encapsulation efficiency were increased. FITC-dextran diffused out of the impregnated microspheres in a slow rate in deionised water, while in presence of sodium ions, its release rate was increased as a consequence of the progressive swelling and erosion of calcium alginate. Release studies from different formulations of impregnated microspheres were performed in a continuous flow apparatus. The release profiles were composed of a slow release phase explained by the progressive erosion of calcium alginate and a faster release phase related to eroded impregnated microspheres. Therefore, the delayed release by microspheres induced by impregnation would permit the delivery of their payload at the vascular occlusion site, limit the amount of drug lost in the systemic circulation and improve the therapy.

Alginates↗

PubMed2004

Indomethacin release from ion-exchange microspheres: impregnation with alginate reduces release rate.

Ion-exchange microspheres (MS) designed as a drug delivery system for embolization coupling ability to occlude vessels and chemotherapy were used to evaluate a manufacturing process allowing to control the drug release rate through reduction of diffusion rate of the drug within the particle by impregnation of calcium alginate inside the porous MS. Impregnation was performed by diffusion of sodium alginate inside DEAE-Trisacryl(R) MS, dispersion of the MS in deionised water and gelling alginate by adding CaCl(2) to the dispersed MS. Studied parameters were alginate concentration, alginate diffusion time and calcium concentration. Indomethacin was loaded into the MS by eluting an aqueous indomethacin solution through a chromatographic column packed with impregnated MS. Indomethacin loading was reduced by alginate. Swelling studies showed indomethacin loading enhanced the hydrophobicity of MS while impregnation had no effect. This had an incidence on indomethacin release rate, which was assessed using the rapid elution of PBS through loaded impregnated MS packed in a column. Indomethacin loading reduced its own rate of release. MS impregnated with 2% w/v alginate gelled with a 40 mM calcium solution presented the lower release rate. This work indicated the manufacturing conditions to display a calcium alginate matrix effect on indomethacin release from DEAE-Trisacryl MS.

Alginates↗

PubMed2004

Production of Carbopol 974P and Carbopol 971P pellets by extrusion-spheronization: optimization of the processing parameters and water content.

Pellets obtained by extrusion-spheronization represent multiparticulate dosage forms whose interest in intestinal drug delivery can be potentiated and targeted through bioadhesive properties. However, adhesion itself makes the process difficult or even impossible. The problem of tackiness encountered with bioadhesive wet masses was previously eliminated by the use of electrolytes such as CaCl2. This approach is known to reduce the viscosity of polyacrylic acids by disturbing the interactions between carboxylate groups on adjacent polymer molecules, thereby decreasing their bioadhesive properties. The present study aimed at producing pellets containing carbomers without addition of electrolytes in order to maintain their bioadhesive potentiality at its maximum. Carbopol 974P (10%, 15% and 20%) and Carbopol 971P (10%) were used in combination with Avicel PH101. The extrusion speed (30, 45, 60, 90, and 150 rpm), spheronizer speed (350, 700, 960, 1000, and 1300 rpm), spheronization time (5, 10, 15, and 20 minutes) and amount of water (45%, 50%, 54%, and 58%) were optimized in order to obtain the highest yield of spherical pellets ranging 710-1000 microm in diameter. For pellets containing 10%, 15% Carbopol 974P or 10% Carbopol 971P and 45% water content, 30 rpm extrusion speed, 960 rpm, and 10 minutes spheronization speed and time led to the highest yields and sphericities, respectively, 72% and 0.91, 67% and 0.78, and 76% and 0.80. Production of pellets with 20% Carbopol 974P could be achieved through the increase of the water content up to 58% and implementation of 30 rpm extrusion speed, 1300 rpm, and 10 minutes spheronization speed and time. The yield and sphericity were 42% and 0.78 respectively.

Acrylates↗

PubMed2003

Effect of apoE/ATP-containing liposomes on hepatic energy state.

BACKGROUND/AIMS: ATP-containing liposomes partially prevent ATP depletion in the cold-stored liver. As hepatocytes can specifically bind apoE, we investigated whether the addition of apoE to large (200 nm) ATP-containing liposomes increases their uptake by the liver and further improves hepatic energy stores. METHODS: Livers from fasted male Hartley guinea-pigs (231 +/- 3 g) were perfused for 90 min under our standard conditions (Control, n = 6) or after a single bolus addition of plain liposomes (Lip, n = 6), ATP (5 micromol)-containing liposomes (ATP-Lip, n = 6) or apoE/ATP-containing liposomes (0.8 or 8mg apoE/g phospholipids; apoE1-Lip and apoE10-Lip, respectively, n = 6 in each group). Liposome uptake and its impact on energy and nitrogen metabolism were studied. RESULTS: At its highest concentration, apoE significantly increased liposome uptake (apoE10-Lip: - 9.17 +/- 0.69 vs apoE1-Lip: - 6.18 +/- 0.44 vs ATP-Lip: - 6.40 +/- 0.88 nmol min(-1) g(-1) P < 0.05). This was associated with a significant increase in intrahepatic ATP (apoE10-Lip: 1033 +/- 137 vs apoE1-Lip: 811 +/- 98 and ATP-Lip: 648 +/- 36 nmol g(-1); P < 0.05), which was restored to its level in non-perfused livers. Hepatic viability and nitrogen metabolism were not affected. CONCLUSIONS: Hepatic ATP content being a key factor in the maintenance of liver graft function, apoE/ATP-containing liposomes should be useful in liver preservation for transplantation.

Adenosine Triphosphate↗

PubMed2002

Hepatic preservation, liposomally entrapped adenosine triphosphate and nitric oxide production: a study of energy state and protein metabolism in the cold-stored rat liver.

BACKGROUND: Liposomally entrapped adenosine triphosphate (ATP) has been demonstrated to improve energy state and function of the cold-stored liver. The increased nitrite release associated with liposome administration led us to investigate the interactions between liposome supply and nitric oxide (NO) production through the use of L-NAME, a non-selective inhibitor of NO synthesis. METHODS: Twenty-four livers from fasted rats were stored for 18 h at +4 degrees C in University of Wisconsin solution directly (control group) or after infusion with ATP-containing liposomes (Lip-ATP), L-NAME (L-NAME) or both (Lip-ATP-L-NAME). Metabolic fluxes, cell volume and energy state were studied during reperfusion. RESULTS: After storage, nitrite release was increased by 61% in the Lip-ATP group, markedly decreased in the Lip-ATP-L-NAME group and almost abolished in the L-NAME group. The ATP content was increased by 20% in the Lip-ATP group (P < 0.05 versus control) and on reperfusion this was associated with an increase in cell volume (17%; P < 0.05) and a decrease in branched-chain amino acid release (21%; P < 0.01). The simultaneous addition of L-NAME did not affect these results, but induced a large (6-fold) increase in glucose production, possibly related to the metabolism of glycerol supplied by the liposomes. In the L-NAME group, global amino acid release was 50% lower and was associated with a dramatic decrease in urea production while the energy state deteriorated rapidly. CONCLUSIONS: The improvement in energy state and anabolic cell swelling induced by ATP-containing liposomes seems to be independent of NO synthesis. On the other hand, inhibition of NO synthesis appears to exert a detrimental effect on the liver, presumably through the decrease in hepatic energy content.

Adenosine Triphosphate↗

PubMed2001

XAS applied to pharmaceuticals: drug administration and bioavailability.

We present selected XAS applications, focused towards practical hospital questions of drug administration and bioavailability, where the technique is driven up to its limits of sensitivity. i) XAS was used to study the interactions between the components of parenteral nutrition solutions, in particular zinc and aminoacids, possibly modifying their bioavailability. ii) We studied by EXAFS a series of binary and ternary copper-aminoacid complexes, in view of the development of an efficient oral drug against copper deficiencies in Menkes disease. iii) EXAFS and XANES analysis allowed us to characterise the solution form of a new arsenic containing drug against leukaemia. In parallel to the XAS measurements, we analysed trace elements levels along patients' hairs, using X-ray fluorescence excited by synchrotron radiation. The measurements along the hair allow for a monitoring of essential trace elements during therapy.

Arsenic Trioxide↗

PubMed2001

Poloxamer 407 as a thermogelling and adhesive polymer for rectal administration of short-chain fatty acids.

OBJECTIVES: The purpose of the study was to gel a rectal solution of short-chain fatty acids to decrease the loss of active materials in the colonic lumen and thereby optimize their absorption. METHODS: Five thermogels were prepared with poloxamer 407 at concentrations ranging from 17% to 20%. Their viscosities were measured at room temperature and 37 degrees C, and their gelling temperatures were determined. The adhesive properties of each gel were assessed in vitro at 37 degrees C. Short-chain fatty acid release was studied using Guyot cells. RESULTS: From the threshold concentration of 17.5%, the solutions, Newtonian at room temperature (50-80 mPa x s), gelled at 37 degrees C. The higher the concentration, the higher the viscosity (1750 to 49,000 mPa x s), the lower the gelling temperature (27.6 degrees C to 23.4 degrees C), and the stronger the work of adhesion (2.2 to 4.5 mJ). Short-chain fatty acid release from the 18% polymer gel was decreased by 60% compared to the rectal solution. CONCLUSION: The 18% poloxamer 407 concentration provided a solution that was liquid at room temperature, that gelled at 37 degrees C, possessed adhesive properties, and controlled short-chain fatty acid release.

Absorption↗

PubMed2001

Colonic delivery of sodium butyrate via oral route: acrylic coating design of pellets and in vivo evaluation in rats.

Few pharmaceutical studies, with the exception of those on rectal solutions, are described on short chain fatty acid (SCFA) formulations-especially for sodium butyrate, which is a colonocyte preferential substrate. Highly dosed butyrate pellets (90%) were prepared and their coating was designed for colonic delivery. In vivo determination (pH and transit time of pellets in rats) allowed to respectively choose the grade and thickness (resistance of 6 h) of the pH-dependent coating (Eudragi L+S, 1:1). The coated pellets were administered to naturally butyrate-deprived rats. The rats' colonic mucosa had the particularity to weakly express mitochondrial HMG-CoA synthase, an enzyme that responds to luminal butyrate. The results did not show early absorption of butyrate, but a probable cecal loss in the rat cecum as cecal residence time of the pellets was important and as pH was propitious for the coating hydrolysis. It seemed that butyrate, given daily for 7 days without the other main SCFA. was unable to induce the enzyme and/or that the dose (0.32 mmol/day) was insufficient.

Administration, Oral↗

PubMed2000

Cold preservation injury in rat liver: effect of liposomally-entrapped adenosine triphosphate.

BACKGROUND/AIMS: Energy charge and capacity for adenosine triphosphate (ATP) synthesis have been demonstrated to play a major role in the maintenance of organ function after liver preservation for transplantation. The aim of this study was to evaluate whether a supply of liposomally-entrapped ATP during preservation could improve the energy state and metabolism of cold-stored rat liver. METHODS: In the first set of experiments, the uptake of ATP-containing liposomes and their effects on hepatic viability were determined in isolated perfused unstored rat liver. In the second set of experiments, rat livers were preserved for 18 h at 4 degrees C in UW solution in the presence of these liposomes, and effects on energy state, cell volume and metabolism were evaluated. In each part, data were compared with adequate control, unloaded liposome-treated, and free ATP-treated groups (n=6 in each group). RESULTS: In non-stored livers, ATP-containing liposomes were taken up by the liver; they did not alter hepatic viability and induced a decrease in energy substrate consumption (glucose and amino acids), and an improvement in intrahepatic ATP content (+23% vs. Control). Addition of liposomally-entrapped ATP during cold storage produced a significant attenuation of the decrease in hepatic ATP content (Lip ATP 2: 524+/-45 vs. Control 2: 364+/-106 nmol/g; p<0.05), and induced, during reperfusion, a decrease in proteolysis associated with an increase in cell volume compared with the other groups (Lip ATP 2: 633+/-63 vs. Control 2: 532+/-38, Unloaded Lip 2: 483+/-55 and Free ATP 2: 500+/-29 microl/g; p<0.01). CONCLUSIONS: These data indicate that liposomally-entrapped ATP represents an effective means to improve liver graft energy state and function. The decrease in protein degradation may be related to the modification of cell volume.

Adenosine Triphosphate↗

PubMed2000

Prevention of proteolysis in cold-stored rat liver by addition of amino acids to the preservation solution.

BACKGROUND: One process identified as detrimental in liver preservation is proteolysis. METHODS: We tested the effects of adding antiproteolytic amino acids (L-alanine, L-glutamine, L-histidine, L-leucine, L-methionine, L-phenylalanine, L-proline, L-tryptophan) to the preservation medium, in a model of reperfusion of 24 h cold-stored rat livers. RESULTS: During the preservation period, antiproteolytic amino acids inhibited the proteolysis observed in stored livers as shown by branched-chain amino acid fluxes, which switched from release to uptake. During reperfusion, cold storage of lives without the addition of antiproteolytic amino acids resulted in a decrease in the total amino acid and branched-chain amino acid uptake and a lower perfusion flow rate. The addition of antiproteolytic amino acids during liver storage resulted in the maintenance of total amino acid and branched-chain amino acid uptake and a significant improvement in the perfusion flow rate during reperfusion. CONCLUSIONS: The presence of antiproteolytic amino acids in the preservation medium might be of interest in improving hepatic graft viability in transplantation.

Amino Acids↗

PubMed1999

Microencapsulation of lipophilic drugs in chitosan-coated alginate microspheres.

Chitosan-coated alginate microspheres containing a lipophilic marker dissolved in an edible oil, were prepared by emulsification/internal gelation and the potential use as an oral controlled release system investigated. Microsphere formation involved dispersing a lipophilic marker dissolved in soybean oil into an alginate solution containing insoluble calcium carbonate microcrystals. The dispersion was then emulsified in silicone oil to form an O/W/O multiple phase emulsion. Addition of an oil soluble acid released calcium from carbonate complex for gelation of the alginate. Chitosan was then applied as a membrane coat to increase the mechanical strength and stabilize the microspheres in simulated intestinal media. Parameters studied included encapsulation yield, alginate concentration, chitosan molecular weight and membrane formation time. Mean diameters ranging from 500 to 800 micron and encapsulation yields ranging from 60 to 80% were obtained. Minimal marker release was observed under simulated gastric conditions, and rapid release was triggered by transfer into simulated intestinal fluid. Higher overall levels of release were obtained with uncoated microspheres, possibly due to binding of marker to the chitosan membrane coat. However the slower rate of release from coated microspheres was felt better suited as a delivery vehicle for oil soluble drugs.

Alginates↗

PubMed1999

Gastrointestinal transit of pellets in rats: effect of size and density.

Gastrointestinal distribution kinetics of a large amount (0.5-1 g) of three types of non-disintegrating pellets which had the same size (S1, 710-1000 micrometers) but different densities (D1, 0.9 and D2, 1.5 g cm-3), or which had the same density (D1) but different diameters (S1 and S2, 1250-1600 micrometers) were examined in fed rats. The percentage of pellets remaining in the stomach, small gut, caecum and colon was measured at suitable intervals. Whatever the size of the pellets, the heavier the density, the longer the gastric emptying (2.1 h for D2-S1 instead of 1.3 h for D1-S1 and 0.7 h for D1-S2). The small gut transit time was not influenced by density but was slightly prolonged by size: 3.3 h for D1-S2 instead of 2.6 h for D1-S1 and D2-S1. Conversely, the gastrocolonic transit time was widely influenced by density (13.5 h for D2-S1) and somewhat by size (8.2 h for D1-S2 and 4.5 h for D1-S1). This delays were proportional to caecal residence time in the large, sacculated and derivated caecum of rats. In order to use the rat as an experimental model for pharmaceutical pellets, those results should have implication for the design of dosage forms, particularly those for controlled or timed release or those for targeted release at specific positions in the gastrointestinal tract.

Animals↗

PubMed1998

Effect of the granulation process on nitrofurantoin granule characteristics.

We studied four granulation methods on the same quantitative and qualitative formula: wet massing by forced agglomeration (Lödige) and free agglomeration (Glatt); and dry massing by slugging and roller compaction technique. Three different particle sizes of nitrofurantoin (bioinequivalent drug) were used. The nitrofurantoin particle size has a very low influence on the physical characteristics of the granules. The granulating process influenced the binding of the particles. Granules processed using the wet granulating method were harder than those made by dry process. Lödige granules were more bonded than Glatt granules. Granules prepared by dry massing presented broken particles. The surface area and the porosity of Glatt granules were the most important parameters. Dissolution studies must be effected to make a correlation between the physical results and the dissolution rates. It is necessary to effect a new validation and a comparison of the results when a new granulating apparatus is used.

Anti-Infective Agents, Urinary↗

PubMed1998

Small-scale characterization of wet powder masses suitable for extrusion-spheronization.

The method of compresso-rheology with an Instron 5567 was used for flow assessment of wet powder mass in order to improve its formulation. In our experiments, the method was efficient for selection of the excipient (Avicel CL611) able to improve the extrusion behavior of the high-dose wet powder mass. The method also allowed the determination of the minima and maxima of the wetting agent volume necessary to identify the correct moisture content for extrusion (20%). The results were not discriminative for the choice of the Avicel CL611 amount in the formulae even if an average amount necessary to improve extrudability of the active ingredient could have been estimated at about 10%. Nevertheless, this method appeared to be a rapid and easy small-scale method for studying wet powder mass, cause only a few grams of solids are required, this rheometer should prove useful in formulation research.

Butyric Acid↗

PubMed1998

Micronization: a method of improving the bioavailability of poorly soluble drugs.

For poorly soluble drugs, the digestive absorption depends on their rate of dissolution. Decreasing the particle size of these drugs improves their rate of dissolution. Fine grinding mills are use to micronize powders: either jar mills or fluid energy mills. Theses processes were applied to griseofulvin, progesterone, spironolactone and diosmin. For each drug, micronization improved their digestive absorption, and consequently their bioavailability and clinical efficacy.

Biological Availability↗

PubMed1997

Deletion of hydroxyethylstarch from University of Wisconsin solution induces cell shrinkage and proteolysis during and after cold storage of rat liver.

Among the numerous components of the University of Wisconsin (UW) solution used for organ preservation, the usefulness of hydroxyethylstarch (HES), the colloido-osmotic support of this solution, is controversial. The aim of our study was to determine the influence of HES on hepatic metabolism and intracellular hydration state during hypothermic preservation and after reperfusion in a model of isolated perfused rat liver. Three groups of eight livers were perfused either immediately or after 18 hours of cold storage in a UW-based preservation solution with or without HES. Omission of HES results in 1) a stimulation of protein degradation shown by the marked increase in branched-chain amino acid (BCAA) release (211 +/- 55 vs. 87 +/- 28 nmol/min/g; P < .05, modified UW group vs. UW group), 2) an increase in oxygen consumption (81.7 +/- 4.8 vs. 61.5 +/- 5.0 micromol/h/g; P < .05), 3) a decrease in glucose production (2.3 +/- 0.6 vs. 5.0 +/- 0.6 micromol/min/g; P < .05), and 4) a reduction in intracellular volume (414 +/- 36 vs. 557 +/- 41 microL/g; P < .05). We conclude that HES plays an important role in liver preservation by limiting proteolysis, possibly through the observed preservation of cell volume.

Animals↗

PubMed1996

Could oral erythromycin optimize high energy continuous enteral nutrition?

BACKGROUND: Intravenous erythromycin has previously been reported to stimulate gastric emptying, to inhibit gastric acid secretion and to stimulate pancreatic secretion during continuous gastric infusion of a liquid diet in healthy volunteers. AIM: The aim of this study was to evaluate the effects of oral erythromycin (160 mg/h) on gastrointestinal function under these conditions in seven healthy subjects. METHOD: This randomized double-blind cross-over study measured the gastric emptying rate of nutrients, gastric acid secretion, gastric pH, jejunal flow rate as well as biliopancreatic secretion and duodeno-caecal transit time during a 19.9 kJ/min continuous infusion of a nutrient solution (4.18 kJ/mL) in the antrum over a 6-h period by a perfusion method. RESULTS: The nutrition was well tolerated except by one subject with placebo perfusion. During the 6-period, total gastric volume and gastric volume of nutrient decreased during erythromycin administration by 22 +/- 8 and 22 +/- 6%, respectively. Gastric acid secretion was not modified by erythromycin. Lipase and bile salt outputs were significantly higher with erythromycin. The duodeno-caecal transit time was not statistically different with drug and placebo (169 +/- 15 and 146 +/- 19 min, respectively). CONCLUSION: During continuous gastric infusion of a liquid diet, the effect of oral erythromycin on gastric emptying could be useful to optimize cyclic enteral nutrition or to enhance the tolerance of enteral nutrition.

Administration, Oral↗