Biomedical subjects

J Smeyers-Verbeke

Publications and source records attributed to J Smeyers-Verbeke.

At least 19 recordsLinked to original sources

PubMed2002

Non-linear mixed effects models for the evaluation of dissolution profiles.

The use of non-linear mixed effects models to describe dissolution data has been evaluated. A theoretical part is included to introduce this approach to scientists who are not familiar with this type of statistics. The standard settings of the statistical software package (S-plus) are used as much as possible. Several mathematical functions like the Weibull, logistic, first-order and Gompertz are employed as basis for the non-linear mixed effects models. Examples are given using dissolution data of immediate and extended release tablets. The results are compared with those obtained using linear mixed effects models.

Linear Models↗

PubMed2001

Application of linear mixed effects models to the evaluation of dissolution profiles.

The performance of linear mixed effects models for the comparison of dissolution profiles is examined. This type of model is frequently used by statisticians, but is rather unknown to people that work in dissolution laboratories. Hence, an extensive theoretical part was introduced to make the methodology more accessible. Firstly, repeated measures ANOVA is discussed, followed by the "real" linear mixed effects models. The theory is applied to two types of dissolution data: one corresponding to an immediate and another to a slow release formulation. We tried to use as much as possible the standard settings of the statistical software (S-plus). Suggestions are given to solve problems encountered during model fitting. It was found that the statistical limits are much more discriminative than the similarity factor.

Analysis of Variance↗

PubMed2001

Evaluation of dissolution profiles using principal component analysis.

The performance of principal component analysis (PCA) for the evaluation of dissolution profiles is examined and compared with other methods such as the similarity factor and the calculation of the area under the curve. Both simulated and real data from the pharmaceutical industry are used. The PCA scores plots of the dissolution curves provide information about the between- and within-batch variations. Differences in level or shape can be observed in the first two principal components (PCs). Irrelevant irregularities, which have a strong influence on the similarity factor, are neglected in PC1/PC2. To detect outliers in a set of dissolution curves, PCA was preferred above Hotelling's T2 test. In general, PCA is found to be a useful technique to examine dissolution data visually, but however, it does not contain criteria to decide if batches are similar or not. This can be done by combining PCA with the resampling with replacement or bootstrap method to construct confidence limits.

Solubility↗

PubMed2001

Guidance for robustness/ruggedness tests in method validation.

This paper is intended to give guidance in setting-up and interpreting a robustness test. The different steps in a robustness test are discussed and illustrated with examples. The recommendations given for the different steps are based on approaches found in the literature, several case studies performed by the authors and discussions of the authors within a commission of the French SFSTP (Société Française des Sciences et Techniques Pharmaceutiques). In the end of the paper a worked-out example is given of a robustness test case study set up and interpreted according to the guidelines.

Chemistry, Pharmaceutical↗

PubMed2000

Supersaturated designs for robustness testing

Supersaturated designs are factorial designs in which the number of factors examined exceeds the number of experiments performed. They do not allow an estimation of individual effects, since even the main effects are confounded. However, the total variance of a response estimated from such a design can in principle be used as a measure for the robustness of the method. A number of case studies were examined to determine whether the variance estimated from a supersaturated design is similar to the one from a Plackett-Burman design. This was found to be the case, which means that the estimated variance describes well the variation in the response caused by the variation in the factors.

Journal Article↗

PubMed2000

Robustness testing of a reversed-phase high-performance liquid chromatographic assay: comparison of fractional and asymmetrical factorial designs.

Robustness tests were performed on a reversed-phase HPLC assay for triadimenol. Different experimental designs were compared. Two-level fractional factorial designs with different resolutions were used to study the influence of procedure-related factors. The factors chromatographic column manufacturer at four levels and instrument at three levels were stepwise included in the study using asymmetrical factorial designs. The significance of the factor effects was determined statistically, using two types of error estimates in the calculation of critical effects, and graphically, by means of half-normal plots. The asymmetrical designs turned out to be an efficient and economic method to examine the influence of factors at different numbers of levels in the robustness testing of analytical methods.

Chromatography, High Pressure Liquid↗

PubMed1999

Evaluation of the H-point standard additions method (HPSAM) and the generalized H-point standard additions method (GHPSAM) for the UV-analysis of two-component mixtures.

The H-point standard additions method (HPSAM) and two versions of the generalized H-point standard additions method (GHPSAM) are evaluated for the UV-analysis of two-component mixtures. Synthetic mixtures of anhydrous caffeine and phenazone as well as of atovaquone and proguanil hydrochloride were used. Furthermore, the method was applied to pharmaceutical formulations that contain these compounds as active drug substances. This paper shows both the difficulties that are related to the methods and the conditions by which acceptable results can be obtained.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

Validation of bioanalytical chromatographic methods.

A strategy is discussed for the validation of chromatographic methods that are developed to quantify drugs in biological matrices. Both the validation terminology and the hypothesis testing are briefly reviewed. The emphasis is on the design of the experiments required to allow a reliable conclusion about acceptance or rejection of the bioanalytical method. In particular, it is explained how to evaluate the calibration line, devise experiments to estimate precision and bias and how to determine the stability of the analyte between the time of the sample collection and the analysis of the processed sample.

Algorithms↗

PubMed1997

Soluble denture adhesives: pH and sodium content.

Seventeen soluble denture adhesives available in local drug stores in Belgium were selected. The pH of aqueous adhesive solutions was determined with a glass pH electrode. Sodium determinations of normal and acidified aqueous adhesive solutions were performed by means of atomic emission spectrometry. The amount of adhesive required per application according to manufacturer's instructions was determined by weight. Gum karaya containing adhesives had an acidic pH (pH < 5). The other adhesive formulations had a pH of about 7. No sodium was detected in gum karaya containing powder adhesives. The sodium content of the other adhesive formulations varied between 1.1 and 8.7 g/100 g. The amount of powder adhesive required for an application in an upper and lower complete denture was respectively 0.2 g and 0.1 g. To provide a denture with a cream or liquid adhesive 0.2 to 0.3 g material was required. Based on the data from this study it was calculated that denture adhesive applications three times a day in both upper and lower complete denture could result in a supplementary daily sodium intake of 0.9 to 6.0 mmol Na+/day.

Adhesives↗

PubMed1996

Selection of reference or test materials for the validation of atomic absorption food analysis methods.

A strategy to select reference or other test materials on which method validation experiments should be performed is developed for the AAs analysis of foodstuffs. Representative materials are selected for each category of food (meat, cereals, vegetables, etc.) and for the complete food spectrum. A principal component analysis and two cluster analysis procedures are applied to accomplish this.

Cluster Analysis↗

PubMed1992

Spuriously low concentrations of serum iron measured with generation 14 Kodak Ektachem slides: prevalence, possible causes, and partial improvement with generation 16 slides.

For sera with iron (Fe) concentrations < 4 mumol/L, Kodak Ektachem slides Generation (GEN) 14 (without ascorbic acid) yielded systematically lower results for Fe than did liquid Ferrozine-based reagents from Baker containing ascorbic acid (10 g/L, final concentration) and adapted to Cobas-Bio. During an 8-month comparison period, outliers (defined as [Fe]Cobas - [Fe]Kodak > 4 mumol/L) were seen in 21 of the 8731 sera (0.24%) tested, corresponding to < 5% of the sera with [Fe]Kodak < 4 mumol/L. In vitro addition of ascorbic acid and (or) Fe identified at least two types of outliers: type 1 (approximately 70%), characterized by [Fe]Kodak > 0.4 mumol/L, by (supra)normal Fe recovery in Kodak slides in the presence or absence of ascorbic acid (10 g/L), and by between-method differences in serum Fe (Cobas - Kodak) that were significantly correlated with serum Zn content (P < 0.0004); and type 2 (approximately 30%), tentatively ascribed to contamination by EDTA, with serum Fe by Kodak < 0.4 mumol/L and Fe recovery near 0%, both of which could be significantly and dose-dependently increased by addition of ascorbic acid (5-20 g/L). For both types of outliers, flameless atomic absorption spectrometry (AAS) yielded results that were significantly higher than concentrations by Kodak with GEN 14. Use of GEN 16 slides (containing ascorbic acid) improved concordance of Kodak results with Cobas, and hence with flameless AAS, for both types of outliers; abolished Zn dependency of results; and increased Fe results in sera with type 2 outliers, although these remained substantially lower than by Cobas. However, like other ascorbic acid-containing reagents, GEN 16 slides were more sensitive to interference by dextran-bound Fe, as assessed during in vitro addition experiments and comparisons involving samples from Fe-dextran-treated patients. GEN 16 slides are hence expected to more frequently overestimate the physiologically available protein-bound Fe in hemodialysis patients. In hospital laboratories, this new interference will probably arise more frequently than the spuriously low results with GEN 14, hence warranting further efforts in optimizing Fe slides.

Ascorbic Acid↗

PubMed1991

Effectiveness of palladium matrix modification for the determination of thallium by graphite furnace atomic absorption spectrometry.

The effect of palladium matrix modification on the determination of thallium has been investigated. The effect of palladium combined either with ammonium nitrate or with magnesium nitrate on the sodium chloride interference was systematically studied and was compared with that of the classical sulfuric acid modifier. A combination of 6 micrograms palladium with 100 micrograms ammonium nitrate allows the direct determination of thallium in ten-fold diluted blood against matrix-free standards. The detection limit (3 sigma) in the undiluted blood was calculated to be 25 micrograms.1(-1). For the urine analysis the standard addition technique is recommended because a complete thallium recovery for all different urine samples studied was not always obtained.

Hot Temperature↗

PubMed1991

Model for assessment of lead content in human surface enamel.

Acid etch surface enamel microbiopsies were taken in vitro and in vivo and analyzed for lead using electrothermal atomic absorption spectrometry. The in vitro samples were obtained from subjects resident in an urbanized region in Belgium or from a region close to a nonferrometal industrial plant. The smaller set of in vivo samples were all from subjects resident in an urbanized region. Using a regression tree approach it was possible to identify in a stepwise manner factors that contributed to the variation of lead in the samples. For the in vitro as well as in vivo samples, the etch depth, tooth type, and age of the subjects were identified as significant factors but sex and dental arch quadrant were not. The residual lead levels obtained after regression with the significant factors were better distributed with much lesser variance. Moreover, a significant higher lead concentration could be demonstrated in the in vitro samples from the region close to the nonferrometal industrial plant.

Dental Enamel↗

PubMed1989

Vitamin D, desferrioxamine and aluminum-induced bone disease in uremic rats.

The effect of 100 ng 1 alpha-OH vitamin D/week alone and in combination with desferrioxamine (DFO), 150 mg/week, was evaluated in aluminum loaded uremic rats. Vitamin D (Vit D) caused an increase of Al in muscle and a decrease in serum Al. Bone histology showed mineralization defect and an increase in bone mass, due to an increase in unmineralized bone, induced both by Al and Vit D administration. Treatment with DFO enhanced urinary Al excretion and lowered tissue Al, without inducing major changes of static bone histology. It is concluded that in Al-loaded uremic rats Vit D can redistribute body Al and that both Al and Vit D can cause a mineralization defect. A 6-week treatment with DFO lowers tissue Al without changing significantly static bone parameters.

Aluminum↗

PubMed1988

The effect of desferrioxamine on tissue aluminum concentration and bone histology in aluminum-loaded rats with renal failure.

Aluminum (Al) intoxication is a condition that reponds well to treatment with desferrioxamine (DFO) in humans with renal failure. The present study deals with the effect of DFO administration on the Al concentrations of different tissues and on bone histology in rats with renal failure, loaded with Al. After the Al-loading there is an important increase of Al in serum, (1,103 +/- 355 micrograms/l) (mean +/- SD), bone (116 +/- 14 mg/kg), liver 238 +/- 78 mg/kg) and muscle (8.5 +/- 4.1 mg/kg). Urinary Al excretion averages 287 +/- 68 micrograms/d. Serum biochemistry reveals renal failure and hypercalcemia (3.5 +/- 0.3 mmol/l). The rats were subsequently treated by either placebo or 150 mg DFO per week. The placebo-treated rats show a spontaneous decrease of serum Ca and Al and of liver and muscle Al content. The DFO-treated rats had, compared to the placebo-treated animals, an increase of urinary Al excretion and lower Al concentration in bone and brain. Bone histology after Al-loading shows an increase in osteoid measurement when compared with non-Al-loaded animals with renal failure: osteoid volume 25.6 +/- 13.3% versus 5.0 +/- 2.9% and osteoid index 63.6 +/- 22.1% versus 27.3 +/- 15.3% in Al-loaded and non-Al-loaded animals, respectively. In addition, the aluminon stain covered 89.7 +/- 3.8% of the bone trabeculae of Al-loaded rats. Under placebo treatment the osteoid measurements increase, reflecting a worsening of Al-induced bone disease. DFO therapy did not result in a significant change of the different measurements of bone histology, despite the decrease of aluminon staining to 67.7 +/- 13.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

PubMed1987

Effect of different combinations of calcium, magnesium and phosphate on the inorganic composition of rat molars in vitro.

Second upper molars from 3-day-old rats were cultured by the Trowell method for 14 days. One of each pair of molars was kept as an uncultured control; the other was cultured. Explants were exposed to eight different combinations of Ca, Mg and P additions to BGJb medium. This resulted in eight groups of explants (control, Ca, Mg, P, CaMg, CaP, PMg and CaMgP) and their eight uncultured contralateral groups. The additions were calculated to double the original measured media concentration. Cultured and uncultured germs were analysed for dry weight (D), ash weight (A), Ca, Mg and P content. The organic fraction (D-A) was calculated. The analysis of covariance by means of multiple regression revealed that Ca-addition to the culture medium stimulated D, A, Ca and P in the explants; P-addition was stimulatory for D, A, D-A and P whereas Mg addition was inhibitory for A, D-A and Ca. A positive interaction for all the tooth-germ variables was demonstrated after CaMg addition; an antagonistic effect was found for the tooth-germ variables D, A, Ca and P after CaP addition. The value of the tooth-germ variables at the time of explantation (covariate) had no significant effect on the value for the variables of the explants (except on their P content). The highest absolute values for all the variables were obtained after CaMg and CaMgP additions. Furthermore, taking into consideration morphological results, the addition of CaMgP can be recommended as medium supplement in the organ culture of rat tooth germs.

Animals↗

PubMed1986

The effect of desferrioxamine on concentration and distribution of aluminum in bone.

Aluminum (Al) loaded rats were injected chronically with either desferrioxamine (DFO) or saline. Six rats of each treatment group were sacrificed before and after one, three, and nine months of treatment for determination of tissue and serum Al, and for histological localization of bone Al. Urinary Al was measured during one week before sacrifice. Al loading caused significant elevations of bone (136.2 +/- 22.0 micrograms/g) and liver (114.4 +/- 41.9 micrograms/g) aluminum. Serum Al in DFO-treated animals was not different from their controls (216.4 +/- 80.5 and 226.9 +/- 42.9 micrograms/liter after one month; 151.0 +/- 20.8 and 138.0 +/- 63.9 micrograms/liter after three months; 72.1 +/- 40.7 and 61.6 +/- 14.2 micrograms/liter after nine months in control and DFO-treated animals respectively). Urinary Al excretion in the DFO-treated group was increased at all times as compared to the control rats. A decrease of muscle Al occurred after one month of DFO treatment, but no significant differences of liver and bone Al could be shown between DFO-treated rats and their controls. Al decreased to a comparable degree in all tissues of both DFO and control rats after nine months of treatment. Histomorphometric examination of the bones showed that after one and three months of treatment, significantly less Al was localized at the calcification front of DFO-treated rats compared to their controls (75.6 +/- 6.9% and 53.4 +/- 20.9% after one month; 52.3 +/- 10.2% and 34.8 +/- 10.6% after three months in control and DFO rats respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

PubMed1986

Characteristics of mineralization of rat molar tooth germs in organ culture.

The behaviour of first (M1) and second (M2) upper molars of 3-day-old rats was compared histologically and by measuring several variables (dry and ash weight, Ca, P and Mg content) on cultured teeth and contralateral control teeth (not cultured). New information was gained by additional computations and calculating correlation coefficients between the variables of the control and cultured molars separately and combined. The M2 seems to perform better in culture than the M1. The M2 model revealed possibilities for further standardization.

Animals↗