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Biomedical subjects

J P Remon

Publications and source records attributed to J P Remon.

At least 91 records · Page 5Linked to original sources
PubMed1999

Influence of chopper and mixer speeds and microwave power level during the high-shear granulation process on the final granule characteristics.

Although microwave drying technology has been used extensively, detailed studies in the pharmaceutical field are necessary to model the different operational parameters involved in microwave drying in combination with the high-shear granulation processes. The implications of the chopper and the mixer speeds during the granulation step and the microwave power level during the drying step on the final granule characteristics were investigated. alpha-Lactose monohydrate and microcrystalline cellulose were granulated at three different mixer and chopper speeds in a laboratory-scale high-shear mixer (Mi-Mi-Pro) and dried at three microwave power levels. The dried granules were characterized by friability tests, particle size analysis, bulk and tapped density studies, and porosimetry. Neither the mixer speed nor the chopper speed had a significant influence on the granule friability, which was low for all batches produced. The selected materials and experimental conditions induced a very robust granulation process, but the granule size distribution was influenced by the microwave power level. The reciprocal relationship between the dust formation and the microwave power level was analyzed using a central composite factorial design. The amount of dust remained low in all batches, but it influenced some of the inherent density properties and the volume reduction behavior of the granulation mass. In almost all cases, the Carr index decreased slightly with increasing microwave power. The major granule characteristics were not changed when different mixer or chopper speeds were changed, although the mixer speed did alter the intragranular pore size distribution.

Lactose↗
PubMed1999

A comparison of the inter- and intragranular drug migration in tray- and freeze-dried granules and compacts.

The influence of the drying process (tray- or freeze-drying), the granulation liquid viscosity, and the drying time during tray-drying on the inter- and intragranular migration of both a water-soluble and a poorly water-soluble compound in a granulation mass and in a compact were quantitatively assessed. Quinidine bisulfate (QBS) and riboflavin (RB) were mixed with a model excipient (glass microspheres) and granulated with an aqueous povidone solution. The drug concentration at different locations inside the granulated mass and in the compacts after drying was determined spectrophotometrically. The RB distribution in the compacts was more homogeneous than the QBS distribution. For both drugs it was clear that the intragranular migration decreased as the granulation liquid viscosity increased. The RB distribution in oven-dried granulation masses showed no migration problem, whereas the QBS samples were characterized by drug-enriched outer layers and drug-depleted inner regions, indicating a strong migration phenomenon. The drug distribution in all freeze-dried samples was homogeneous. A homogeneous distribution of a small-dosed water-soluble and a water-insoluble drug in granules and in compacts was obtained by the use of freeze-drying. The intragranular migration of QBS was prevented by the use of twice the amount of binder compared to that in RB compacts.

Desiccation↗
PubMed1998

Liquid chromatographic separation of doxycycline and 4-epidoxycycline in a tissue depletion study of doxycycline in turkeys.

Liver and muscle tissue residues of doxycycline in turkeys were determined following administration of 25 mg doxycycline x HCl/kg BW in the drinking water under field conditions. Quantitation was performed using a validated HPLC method with fluorescence detection. The method was able to separate doxycycline and its 4-epimer, 4-epidoxycycline. This epimer was found in both liver and muscle tissue. The detection limits of the method were estimated at 1.2 ng/g and 1.0 ng/g of doxycycline in liver and muscle tissue, respectively, using a signal-to-noise ratio of 3:1. The recovery of doxycycline was determined from spiked tissues and was 63+/-3.8% and 66+/-3.1% for liver and muscle, respectively (n = 6). Within-day and between-day imprecision, expressed as the R.S.D. was below 7.4%. Linear calibration curves (r>0.997) were obtained in spiked liver between 0 and 1500 ng/g and in spiked muscle between 0 and 500 ng/g. A good stability of doxycycline was observed in liver samples after storage for 22 days at -20 degrees C. The correlation between the residues in the liver and the muscle was expressed as the correlation coefficient r and was 0.9884. The depletion kinetics of doxycycline fitted a one-compartment model. The elimination half-life (T1/2) of doxycycline was 77.7 h and 78.0 h in muscle and liver, respectively. Furthermore, the residue depletion kinetics were used to establish a withdrawal period in conformity with official guidelines. The withdrawal times necessary to reach concentrations below maximum residue limits (MRLs), as imposed by the EU, were 12 days and 17 days for liver and muscle tissue, respectively.

Animals↗
PubMed1998

Variability of morphine disposition during long-term subcutaneous infusion in terminally ill cancer patients.

OBJECTIVE: To study the plasma concentrations of morphine and its glucuronides to assess the intra- and interindividual variability of the disposition of morphine administered by subcutaneous infusion in cancer patients. METHODS: Blood samples were taken repeatedly in eight patients with severe cancer pain who were being treated with morphine (60-3000 mg per day) via chronic (8-160 days) subcutaneous infusion. Venous blood samples were collected at least weekly and, when possible, on 3 consecutive days after dose adaptation or any other major change in the patients' treatment. Concentrations of morphine and its glucuronides in plasma were measured after solid-phase extraction using a validated high-performance liquid chromatography assay. The stability of the morphine solutions was determined by repeated measurement of the concentrations of morphine and its degradation products in the solutions. RESULTS: The morphine concentration in the infusion solutions remained unchanged during storage and infusion. The plasma concentrations of morphine and its glucuronides were within the ranges reported in the literature. There was, as expected, a large interindividual variability: from patient to patient, the mean of the normalised plasma concentrations ranged from 0.3 ng.ml(-1).mg(-1) to 0.8 ng.ml(-1).mg(-1) for morphine, from 1.0 ng.ml(-1).mg(-1) to 3.1 ng.ml(-1).mg(-1) for morphine-6-glucuronide and from 6.8 ng.ml(-1).mg(-1) to 24.3 ng.ml(-1).mg(-1) for morphine-3-glucuronide. Intraindividual variability was also important. The residual standard deviation of the mean normalised plasma concentrations calculated for each patient ranged from 26% to 56% for morphine, from 20% to 51% for morphine-6-glucuronide and from 20% to 49% for morphine-3-glucuronide. The normalised plasma concentrations of morphine and its glucuronides did not increase with dose or time, and no explanation for the pronounced pharmacokinetic intraindividual variability was found. CONCLUSION: During subcutaneous infusion of morphine, there is a large intra- and interindividual variability of the morphine disposition which could be of clinical relevance.

Aged↗
PubMed1998

Pharmacokinetics and efficacy of amoxycillin in the treatment of an experimental Streptococcus bovis infection in racing pigeons (Columba livia).

The pharmacokinetics of amoxycillin in pigeons (Columba livia) and the efficacy of amoxycillin treatment in pigeon streptococcosis, were investigated. After intravenous administration of 150 mg.kg-1 amoxycillin, the drug plasma concentration-time profile fitted an open two-compartment model. Amoxycillin was quickly cleared from the circulation with a mean half-life of 66 min and showed a distribution volume of 0.9 L.kg-1. The absolute oral bioavailability of amoxycillin was 50.1%. A 5-day drinking water treatment with amoxycillin (1500 mg.L-1, corresponding to 112.0 mg.kg-1.day-1 during day-light hours) significantly reduced the postinoculation morbidity in pigeons experimentally infected with Streptococcus bovis, compared to untreated infected controls.

Amoxicillin↗
PubMed1998

Optimization of the processing of matrix pellets based on the combination of waxes and starch using experimental design.

An experimental design was used in order to optimize the one-step production process of matrix pellets based on the combination of waxes and starch. The parameters tested were the impeller speed (x1) and the mixing time (x2). Ibuprofen and theophylline were used as model drugs at a concentration of 60 and 70% (w/w), respectively. The 0.8-1.25 mm yield fraction of the matrix pellets was evaluated as the response factor Y. A quadratic equation was fitted to the experimental data and used to predict the response factor Y of the theophylline and the ibuprofen. The contour plots of both formulations revealed a flat and therefore rugged region from the upper left to the lower right of the domain investigated. The energy input into the system during the production process controlled the pellet growth, the impeller speed having a greater impact on the energy input compared to the mixing time.

Delayed-Action Preparations↗
PubMed1998

Effect of the substrate-binder interactions on the mechanical properties of compacts.

The effect of the substrate-binder interfacial interaction in granules, made of PVP and glass ballotini as model substrates, on the mechanical properties of rectangular compacts consisting of these granules was investigated by use of the four-point beam bending technique. The mechanical properties of the prepared compacts were correlated with the physico-chemical characteristics--contact angle, surface tension and binder concentration--of the granulation liquid. The mechanical strength and Young's modulus of the specimens both reached a maximum value when the binder concentration in the granulation liquid was increased to 20% (w/v) for all granulation liquid volumes used. Above a 20% PVP concentration, the increasing granulation liquid contact angle hindered the binder spreading, creating weak regions in the compact and decreasing its mechanical strength.

Chemistry, Pharmaceutical↗
PubMed1997

Near-infrared (NIR) monitoring of H2O2 vapor concentration during vapor hydrogen peroxide (VHP) sterilisation.

PURPOSE: There is an increasing use in the pharmaceutical industry of barrier systems such as transfer isolators, sterilisation tunnels and work station isolators. As Vapor Hydrogen Peroxide (VHP) sterilisation of isolators and lyophilizers becomes an important sterilisation method, there is an acute need for a VHP monitoring system to be used for in-process control and validation. In this study, near infrared (NIR) spectrofotometry was evaluated as a potential technique to monitor hydrogen peroxide. Additionally the H2O2 vapor permeability of different packaging materials, commonly used in steam and ethylene oxide sterilisation, was evaluated. METHODS: NIR spectrofotometry, using a gas cell connected with optic fibres, was evaluated as a potential technique to monitor hydrogen peroxide vapor and water vapor during VHP sterilisation of an isolator. A NIR spectrum was taken every 30 s during VHP sterilisation of an isolator. The influence of injection rate, air flow rate, working temperature and gas distribution was investigated. The H2O2 vapor permeability of different packaging materials was determined by placing the gas cell in the sterilisation bags and sealing the bags hermetically. The sterilisation bag was then subjected to VHP sterilisation. RESULTS: The NIR spectra taken at steady state sterilization conditions showed 4 absorption peaks: at 1364, 1378 and 1400 nm attributed to water and at 1420 nm attributed to H2O2 vapor. By measuring the absorbance level at these wavelengths, the actual concentration of H2O and H2O2 vapor in the isolator was calculated. The water vapor permeation of the sterilisation bags, measured with NIR, appeared to be equal for all materials tested. Whereas Tyvek was the most permeable material for hydrogen peroxide vapor (82.7% of the reference concentration outside the bag), only 30% was found in bags made of medical paper. Sterilisation bags consisting of laminate films and PVC sealed to medical paper showed intermediate permeability. CONCLUSIONS: Near-infrared (NIR) spectroscopy using a gas cell with optic fibres is a useful technique to monitor VHP sterilisation cycles. There was a difference in H2O2 vapor permeability of different packaging materials, commonly used in steam and ethylene oxide sterilisation.

Hydrogen Peroxide↗
PubMed1997

Administration of doxycycline hydrochloride via drinking water to turkeys under laboratory and field conditions.

A series of experiments were carried out in order to determine doxycycline hydrochloride (DoxHCl) plasma levels in 6-wk-old turkeys medicated via drinking water containing DoxHCl at a concentration of 250 mg/L under laboratory and field conditions. Maximal plasma concentration (Cmax) values of 5.7 (+/-1.0) microgram/mL and 4.9 (+/-1.4) micrograms/mL obtained after DoxHCl administration during 2 and 7 d, respectively, were not significantly different. A significant difference was found between the area under the plasma concentration-time profile, calculated between 0 and 168 h (AUC(0-168)), Cmax, and the minimal plasma concentration (Cmin) values obtained after medication with a DoxHCl solution at a concentration of 250 mg/L (431.9 +/- 96.6 micrograms.h/mL, 4.9 +/- 1.4 micrograms/mL and 0.7 +/- 0.3 microgram/mL) and after medication with a DoxHCl solution at a concentration of 750 mg/L (1,176.5 +/- 201.8 micrograms.h/mL, 12.5 +/- 2.7 micrograms/mL and 2.9 +/- 0.4 micrograms/mL), respectively. The increase in body weight was also significantly higher for turkeys medicated with a DoxHCl solution at a concentration of 750 mg/L (83.7 g/d) than for the lower concentration (35.6 g/d). The DoxHCl solution uptake significantly decreased with the increase of DoxHCl concentration. A Cmax value of 1.7 +/- 0.6 micrograms/mL and a Cmin value of 0.5 +/- 0.1 microgram/mL were observed during the field experiment. Water consumption under laboratory conditions was followed for tap water (70 +/- 50 mL/kg.d) and for a DoxHCl solution at a concentration of 250 mg/L supplemented with 1 g anhydrous citric acid/L (119 +/- 6 mL/kg.d) and revealed to be not significantly different. The variability was significantly higher for tap water than for the DoxHCl solution. The stability of the DoxHCl solution containing 1 g citric acid/L over 24 h was 99% expressed as the percentage of the initial concentration.

Administration, Oral↗
PubMed1997

Chemoprophylaxis of fungal deterioration of the Provox silicone tracheoesophageal prosthesis in postlaryngectomy patients.

A double-blind randomized trial was conducted among 36 laryngectomees to assess the influence of a buccal bioadhesive slow-release tablet containing miconazole nitrate on the lifetime of the Provox voice prosthesis. All patients colonized with Candida spp and treated with miconazole showed a significant decrease of colonization at the end of the study. Intratracheal phonatory pressures were remarkably higher after 2 months of follow-up in the placebo group. No local or systemic adverse reactions to miconazole were observed during this study. Patient compliance was acceptable according to regular miconazole determination in saliva samples. The device lifetime was significantly higher in patients treated with miconazole even after 1 year of follow-up. The use of a buccal bioadhesive slow-release tablet containing an antimycotic agent proves to be an adequate method of preventing fungal colonization and deterioration of silicone voice prostheses.

Adult↗
PubMed1997

Deterioration of the Provox silicone tracheoesophageal voice prosthesis: microbial aspects and structural changes.

Device life of tracheoesophageal voice prostheses is limited due to deterioration of the polymers. A group of 55 postlaryngectomy patients fitted with a Provox voice prosthesis have been studied prospectively during 6 months. Thirty-seven prostheses were replaced due to a dysfunctional valve mechanism. Although colonization with Candida species was highly associated with destruction of the silicone material, other upper respiratory tract commensals, e.g. Staphylococcus aureus, were also demonstrated. Electron microscopy of the contaminated devices showed colonization and disruption of the silicone material by penetrating yeast hyphae. During the study a remarkable increase of intratracheal phonatory pressures was assessed with progressive colonization of the prostheses.

Biocompatible Materials↗
PubMed1996

Validation of a high-performance liquid chromatographic method for the determination of doxycycline in turkey plasma.

A high-performance liquid chromatographic method for the analysis of doxycycline in turkey plasma samples using demeclocycline hydrochloride as the internal standard was developed, optimized and validated. A one-step extraction procedure and an isocratic HPLC method with UV detection were used. No interferences with endogenous compounds or with the anticoagulant were observed. Linear calibration curves (r2 > 0.99) were obtained in water and plasma between 0 and 600 micrograms ml-1. Good recoveries for doxycycline (> 66%) and demeclocycline (> 72%) were seen both in water and in plasma. The coefficient of variation was < 9.86% for within-day reproducibility and < 7.53% for the between-day reproducibility. The deviation between the mean value found and the true value was < 14.5% (accuracy). The limit of detection was 0.1 microgram ml-1 in plasma samples. A good stability of doxycycline was observed in water and in plasma samples after storage for six months at -20 degrees C (recovery > 91%).

Animals↗
PubMed1996

Maltodextrins as lyoprotectants in the lyophilization of a model protein, LDH.

PURPOSE: Maltodextrins, partially hydrolysed starches, were evaluated as potential lyoprotectants and the effect of combinations of maltodextrins and PEG 8000 on the protection of lactate dehydrogenase (LDH) was examined. METHODS: LDH activity assays were performed immediately before freezing and after reconstruction. The activity recovery was used as the parameter to evaluate the lyoprotectants. Differential Scanning Calorimetry (DSC) was used to measure the glass transition temperature (Tg') of the solutions. DSC and X ray diffraction were used to characterise the freeze-dried products. RESULTS: Maltodextrins were found to protect LDH against inactivation during freeze-drying. The lyoprotection obtained by these maltodextrins is dependent on their D.E. value and the concentration used. The maltodextrin formulations performed as good or better than those containing sucrose and maltose, depending on the concentration used. Freeze dried cakes of maltodextrin formulations were amorphous. In the case of low D.E. maltodextrins, lyoprotection was improved by the addition of PEG 8000 as a cryoprotectant. CONCLUSIONS: Maltodextrins could be considered as potential lyoprotectants in lyophilization of proteins.

Animals↗
PubMed1996

Buccal absorption of testosterone and its esters using a bioadhesive tablet in dogs.

PURPOSE: As the oral bioavailability of testosterone is very low because of its high first pass effect, buccal administration might present a viable alternative. In this study a buccal bioadhesive tablet was used in order to sustain the delivery and bypass the liver. METHODS: Testosterone and testosterone acetate, propionate, enanthate and decanoate were investigated. The influence of the concentration of testosterone (10-50%) and testosterone esters (30%) on in vitro bioadhesion was investigated. The absolute (i.v.) and relative (oral) bioavailability of 60 mg testosterone or an equivalent amount of testosterone ester was determined in castrated male dogs. RESULTS: Both the in vitro detachment force and the work of adhesion decreased gradually with an increasing amount of testosterone and for an increasing chain length of the esters, except in the case of testosterone enanthate. The in vivo results revealed that the bioavailability of testosterone was significantly higher (p < 0.05) than that of the esters, which is probably due to the lower solubility of the esters. The mean absolute bioavailability of testosterone from the bioadhesive tablet was 14.1%, while the mean relative bioavailability was 1370%. The buccal administration of testosterone via the bioadhesive tablet allowed the maintenance of the plasma level at above 3 ng/ml for 15 to 24 h. CONCLUSIONS: Buccal absorption of testosterone was significantly higher than that of its esters.

Administration, Oral↗