Biomedical subjects

Chris Vervaet

Publications and source records attributed to Chris Vervaet.

15 recordsLinked to original sources

PubMed2006

Development of starch-based pellets via extrusion/spheronisation.

A modified starch (high-amylose, crystalline and resistant starch) was evaluated as an alternative excipient to microcrystalline cellulose for pellets prepared via extrusion/spheronisation. Theophylline anhydrous (25%, w/w) was used as a model drug. A binder was necessary to obtain an acceptable yield and the addition of sorbitol improved the surface properties of the pellets. A surface response design with three formulation variables (binder, sorbitol and water level) and one process variable (spheronisation speed) was used to optimise the process and to evaluate pellet yield, sphericity (aspect ratio and two-dimensional shape factor, e(R)), size (mean Feret diameter), friability and disintegration properties. Mixer torque rheometry and solid-state NMR revealed a significant influence of sorbitol on wet mass consistency and pellet properties. A high pellet yield (>90%), acceptable sphericity (AR<1.2), low friability (<0.01%), fast disintegration (<10 min) and complete drug release in less than 20 min for all formulations, demonstrated the potential of this modified starch in formulations intended for extrusion/spheronisation.

Algorithms↗

PubMed2006

Melt granulation using a twin-screw extruder: a case study.

The purpose of this study was to use a twin-screw extruder for melt granulation. Polyethylene glycols (PEG 400 and 4000) were used as binders for the development of a drinking water formulation with immediate drug release. The effect of drug content, PEG 400/4000-ratio, surfactant (type and concentration) and granulation temperature on granule properties and dissolution characteristics was determined. The granulation temperature had an important influence on the granule formation. High yield (95% of the granules <1400 microm) was obtained only at a temperature near the melting point of PEG 4000. During granulation the drug of BCS class II was finely dispersed in the PEGs, creating a micro-environment around the drug particles enhancing the dissolution rate. To obtain complete drug release within 10 min for a formulation containing 10% drug, the addition of 2% (w/w) surfactant (polysorbate 80 or Cremophor RH40) was required. At a higher drug content (20%), the PEG 4000 concentration had to be increased to 20% to improve granule properties and 4% polysorbate 80 was required to obtain 100% drug release. X-ray diffractograms showed distinct peaks of crystalline drug, the crystallinity of the drug did not change after 50 days, independent of the storage conditions.

Calorimetry, Differential Scanning↗

PubMed2006

Subjective and objective evaluation of noncultured epidermal cellular grafting for repigmenting vitiligo.

BACKGROUND: Noncultured epidermal cell transplantation in vitiligo permits the coverage of relatively large areas without culturing cells. OBJECTIVE: To investigate the effectiveness of noncultured epidermal cell transplantation in treating stabilized vitiligo using objective and subjective evaluation methods. METHODS: Noncultured autologous melanocytes and keratinocytes were grafted in a hyaluronic-acid-enriched suspension on superficially laser-abraded vitiligo lesions in 40 patients with refractory stable vitiligo (30 with generalized and 10 with localized vitiligo). The repigmentation was evaluated 3-12 months after grafting using a digital image analysis system. Furthermore the treatment was evaluated from the patients' point of view with the DLQI (Dermatology Life Quality Index) and a 'global assessment'. RESULTS: The mean percentage of repigmentation, evaluated at the last follow-up visit, was 72% (median 84%), and a repigmentation of >or=70% was observed in 62% of patients. The best results were achieved in the neck and the presternal region. A subjective evaluation was performed in half of the subjects. The mean DLQI score at inclusion (6.95, SD = 6.68, n = 20) was significantly decreased after treatment (p = 0.013, mean 3.85, SD = 4.13, n = 20). The patients were satisfied with the achieved result, found it worthwhile to undergo the treatment and would choose it again. CONCLUSION: According to both subjective and objective evaluation methods, noncultured epidermal cell transplantation is promising in patients with stable vitiligo.

Adolescent↗

PubMed2005

Liquid chromatographic-mass spectrometric assay for simultaneous pyrimethamine and sulfadoxine determination in human plasma samples.

We present a liquid chromatographic-mass spectrometric assay for the simultaneous determination of sulfadoxine and pyrimethamine in human plasma samples. Sample clean-up was achieved by adding acetonitrile for protein precipitation. Gradient elution in only 10 min resulted in high throughput capability. Tandem mass spectrometric detection in multiple reaction monitoring was used for quantification. The developed analytical approach was successfully validated and was applied in the pharmacokinetic evaluation of the bioavailability between two sulfadoxine/pyrimethamine formulations available on the Eastern African market, using a cross-over design.

Antimalarials↗

PubMed2005

Production of enteric capsules by means of hot-melt extrusion.

The aim of this study was to develop an alternative technique for enteric coating consisting of the hot-melt extrusion of coating polymers. An enteric coating polymer (PVAP or HPMC AS), premixed with a plasticizer, was extruded into hollow cylinders. The hollow pipes were filled with a model drug and both open ends of the cylinders were closed, yielding hot-melt extruded enteric capsules. Main advantages of this new technology are the continuity of the process and its application for the formulation of moisture sensitive active ingredients. The enteric capsules showed excellent gastro-resistance, since no drug release was observed after 2 h 0.1N HCl. The influence of wall thickness (0.15, 0.3, 0.5, 0.8, and 1.0 mm) of the capsules on drug release was investigated. Enteric capsules with a wall thickness of 1.0 mm were subjected to a pH gradient dissolution method, simulating passage through the gastro-intestinal tract, in order to evaluate their suitability for ileal or colonic drug targeting. Storing the capsules for 1 month at high relative humidity (RH) (60 and 75% RH) revealed that the HPMC AS capsules were superior to the PVAP capsules. It can be concluded that hot-melt extruded capsules seem suitable as an alternative for enteric coating.

Capsules↗

PubMed2004

Bioavailability of ibuprofen from hot-melt extruded mini-matrices.

The bioavailability of ibuprofen from hot-melt extruded mini-matrices based on ethyl cellulose and a hydrophilic excipient was tested. During the in vivo evaluation an oral dose of 300 mg ibuprofen was administered to healthy volunteers (n = 9) in a randomized cross-over study and compared with a commercially available sustained release product (Ibu-slow). The plasma samples were analysed by a validated HPLC-UV method. One mini-matrix formulation (F-1) consisted of 30% ibuprofen, 35% ethyl cellulose and 35% hydroxypropyl methylcellulose (Metolose 60 SH 50), while the second formulation (F-2) contained 60% ibuprofen, 20% ethyl cellulose and 20% xanthan gum. These mini-matrices were administered in hard gelatine capsules. Both formulations behaved in vivo as sustained release formulations with an HVD(t50% Cmax) value (time span during which the plasma concentration is at least 50% of the Cmax value) of 7.6 and 12.0 h for formulations F-1 and F-2, respectively, whereas a value of 5.2 h was obtained for Ibu-slow. Although a significantly higher Cmax and AUC(0-24 h) was seen for the reference product, the relative bioavailability of both experimental formulations was about 80%.

Adolescent↗

PubMed2004

Assessment of a new utero-tubal junction insemination device in dairy cattle.

A new artificial insemination device for semen deposition near the utero-tubal junction in cattle (Ghent device) has been developed at the Ghent University (Belgium). In this study, the effect of the new insemination device on sperm quality was evaluated. Moreover, in a field trial 4064 dairy cows were inseminated by 12 inseminators to examine the efficacy of the device under field conditions. The Ghent device is a disposable plastic catheter which can easily follow the curvature of the uterine horns and thus reach the utero-tubal junction (UTJ). After expulsion of the inseminate with 0.7 or 1.7 ml of air, 19.0% of the insemination dose remained in the insemination catheter. Sperm loss can be diminished to 9.0% of the original insemination dose when the insemination catheter is flushed with 0.1 ml of air, followed by 0.6 ml of physiological saline solution. No toxic effect of the insemination catheter on sperm quality or fertilizing capacity was found. In the field trial, sperm were inseminated in dairy cattle which were divided in three groups. The first group was inseminated in the uterine body with the conventional insemination device, the second group in the uterine body with the Ghent device, and the third group in the tip of both uterine horns with the Ghent device. Each insemination was performed with 10 x 10(6) to 15 x 10(6) frozen-thawed spermatozoa. The pregnancy rates (PRs) were significantly affected by the insemination technique (P = 0.02), by the inseminator (P = 0.01), by heifer or cow (P < 0.01), and by the insemination number (P < 0.01). Pregnancy rates obtained with the conventional insemination device (57.6%) were significantly better than those obtained with the Ghent device in the uterine body (52.7%) (P < 0.01), but did not differ significantly from those obtained after deep insemination into both uterine horns (53.8%) (P = 0.27). It can be concluded that the Ghent device is suitable for utero-tubal junction insemination of dairy cattle under field conditions. Whether the Ghent device is also suitable for insemination with lower insemination doses is at present under investigation.

Animals↗

PubMed2004

Double-blind placebo-controlled study of autologous transplanted epidermal cell suspensions for repigmenting vitiligo.

OBJECTIVES: To investigate the efficacy of epidermal noncultured cellular grafting in patients with vitiligo and the role of postinflammatory, spontaneous, or UV-induced pigmentation in obtaining repigmentation. DESIGN: A prospective, randomized, double-blind, placebo-controlled study. SETTING: Ambulatory patients in an institutional practice. Patients were followed up for 3 to 12 months. PATIENTS: A total of 33 paired, symmetrically distributed leukodermic lesions, all resistant to therapy, were observed in 28 patients. Nineteen patients appeared to have a stable vitiligo (group 1), whereas there was doubt about the stability of the disease in 9 patients (group 2). INTERVENTION: After laser ablation, a hyaluronic acid-enriched cellular graft was applied to 1 lesion while the paired lesion received placebo. Three weeks later all lesions were exposed to UV irradiation twice per week for approximately 2 months. MAIN OUTCOME MEASURES: Primarily, the percentage of repigmentation was assessed after 3, 6, and 12 months using a digital image analysis system. The repigmentation pattern was also evaluated after 1 and 3 months. RESULTS: A strongly significant difference between cellular grafts and placebo was observed after 3, 6, and 12 months (P<.001, P = .002, and P = .002, respectively). In group 1, repigmentation of at least 70% of the treated area was achieved in 55%, 57%, and 77% of the actively treated lesions 3, 6, and 12 months after treatment, whereas in group 2 repigmentation of at least 70% of the treated area was not observed at any time point. The repigmentation pattern was diffuse in 94% of the responding patients. CONCLUSIONS: After a strict preoperative selection for disease stability, transplantation resulted in repigmentation of at least 70% of the treated area in most actively treated vitiligo lesions. Repigmentation was primarily caused by the transplanted melanocytes.

Adolescent↗

PubMed2004

Aerosol profile extracted from spacers as a determinant of actual dose.

PURPOSE: We propose a novel method to evaluate the efficacy of a pressurized metered dose inhaler (pMDI) in combination with a spacer, by not only considering the total dose extractable from the spacer but also the dependence of dose on the volume available for aerosol inhalation. METHODS: We studied volume-dependence of aerosol concentration during extraction from two commonly used plastic spacers (150 ml AerochamberPlus; 750 ml Volumatic) after a single puff of a 100 microg salbutamol pMDI (HFA-Ventolin), using laser photometric measurements. RESULTS: After a delay of is in each spacer, the aerosol peak dose for AerochamberPlus was 2-fold that for Volumatic (p < 0.001), with the peak appearing well within the first 0.5 L even for the largest spacer. The opposite dose relationship is reached when considering total cumulative dose, which was 2-fold higher for Volumatic than for AerochamberPlus (p < 0.001); >95% of total cumulative dose was extracted well within 3 L for the largest spacer. The 2-fold cumulative dose relationship was confirmed by chemical assay on an absolute filter [AerochamberPlus: 21.4+/-3.2 (SD) microg; Volumatic: 43.8+/-9.1 (SD) microg]. CONCLUSIONS: Actual aerosol dose available to patients during inhalation via spacers can only be done on the basis of a quantification of aerosol peak dose and cumulative dose as a function of extracted volume.

Administration, Inhalation↗

PubMed2004

Influence of the punch diameter and curvature on the yield pressure of MCC-compacts during Heckel analysis.

The volume reduction behaviour of powders has been quantified by means of the 'in-die' yield pressure (YP) using Heckel analysis. However, because different YPs are reported for the same material, the experimental conditions influencing this material-constant were investigated. Silicified microcrystalline cellulose was compressed into flat-faced and convex tablets using a compaction simulator instrumented with load and displacement transducers. During compression, upper and lower punch force and displacement data were recorded and corrected for punch deformation. A symmetrical triangle wave compression profile was used and the instantaneous punch velocity was kept constant (5mm/s). Individual tablet height and weight were used for Heckel analysis. The influence of the 'effective compression pressure' (P(EFF)) (ranging from 10 to 350 MPa), punch diameter (PD) (4, 9.5 and 12 mm) and filling depth (FD) (4.5, 7.5 and 10.5mm) on YP was statistically evaluated using Response Surface Modelling software. A quadratic surface response equation, describing the relationship between P(EFF), PD, FD and YP, was proposed for concave (Adj R(2): 0.8424; S.D.: 14.60 MPa) and flat-faced (Adj R(2): 0.8409; S.D.: 4.49 MPa) punches. YP and tensile strength were mainly determined by P(EFF), irrespective of punch curvature. FD and PD had only a minor influence on the YP, although more pronounced for the concave punches. The method used resulted in reproducible P(EFF) and tensile strength values and the flat-faced tablets showed less weight variation. Flat-faced punches are preferred over punches with a concave surface when investigating the volume reduction behaviour of a powder by means of Heckel analysis and the experimental parameters should be reported.

Cellulose↗

PubMed2004

Compaction of enteric-coated pellets: influence of formulation and process parameters on tablet properties and in vivo evaluation.

The aim of this study was to investigate the influence of formulation and compression parameters on the properties of tablets, containing enteric-coated pellets, and on the integrity of the enteric polymer of the individual pellets after compression. In addition the piroxicam plasma concentrations were determined after single and multiple oral administration of powder, pellet and tablet formulations at a dose of 0.3 mg piroxicam/kg bodyweight to dogs. Tablets consisted of enteric-coated pellets (containing 2.5% (w/w) piroxicam in combination with microcrystalline cellulose and sodium carboxymethylcellulose (using Avicel PH 101 and Avicel CL 611 in a ratio of 1-3), cushioning waxy pellets and 10% Kollidon CL (as an external disintegrator). From the D-optimality experimental design it was concluded that the ratio of coated pellets to cushioning pellets (CoP/CuP) affected all tablet properties evaluated. Variation of the pellet size and the CoP/CuP ratio resulted in different in vitro tablet disintegration times. Enteric coating of the pellets or compression of the coated pellets did not have a significant influence (P >0.05) on AUC(0-->72 h). Cmax values obtained after oral administration of coated pellets and compressed coated pellets were significantly lower than for the other formulations. Differences in in vitro tablet disintegration times were not reflected in the onset of the piroxicam plasma concentrations. A dosing interval of 48 h prevented piroxicam accumulation following multiple dose administration.

Carboxymethylcellulose Sodium↗

PubMed2002

Near-infrared FT-Raman spectroscopy as a rapid analytical tool for the determination of diltiazem hydrochloride in tablets.

This study was performed to develop a fast and reliable analytical method for the quantitative determination of diltiazem hydrochloride in tablets. HPLC is currently the preferred method, but is time consuming due to extensive sample preparation. FT-Raman spectroscopy was used to quantitatively analyse diltiazem hydrochloride in commercially available tablets (Tildiem) and in experimental tablets prepared at lab-scale. The percentage of diltiazem hydrochloride in each tablet was determined by calculating-after vector normalisation-the total peak area of the spectral band between 1625 and 1560 cm(-1). No spectral interference from tablet excipients was seen at this spectral band. After FT-Raman spectroscopy the same samples were analyzed based on the HPLC method described in the USP XXIV. The drug dosage per tablet obtained from the vibrational spectroscopy method correlated well with the results obtained using HPLC analysis for both the commercial tablets (HPLC: 63.57+/-0.13 mg; Raman: 63.28+/-0.26 mg (n=50)) and the experimental tablets (HPLC: 181.02+/-0.25 mg; Raman: 181.22+/-0.35 mg (n=50)). FT-Raman is a reliable alternative for the HPLC method to quantify the amount of diltiazem hydrochloride in tablets. The spectroscopic method is faster because it eliminates sample pre-treatment. Furthermore the FT-Raman method has an additional advantage of not requiring solvents.

Chromatography, High Pressure Liquid↗

PubMed2002

Scaling-up of a lactose wet granulation process in Mi-Pro high shear mixers.

The high shear wet granulation upscaling possibilities of a Pro-C-epT Mi-Pro 250 ml with a batch size of 40 g were investigated by down-scaling an alpha-lactose monohydrate wet granulation process from a Collette Gral 10 (8 l batch size) to a Pro-C-epT Mi-Pro with different bowl volumes of 5 l, and 1900, 900 and 250 ml. The wet granulation process was optimised in the Gral 10, next an octagonal design was build around the central point. Two process parameters, the impeller tip speed and the water content, were varied at three levels, which resulted in a two-factor three-level experimental design. alpha-Lactose monohydrate 200 M was granulated using a polyvinylpyrollidone K 30 (2.5% on dry material) binder solution. The granules were dried at 25 degrees C for 24 h, sieved and characterised. The granules were compressed to tablets. In all mixer volumes the used impeller tip speed range did not influence the granule or tablet properties. In all bowl volumes the influence of water concentration on actual yield, particle size distribution and granule friability was similar. All batch sizes resulted in tablets of similar quality. For the selected formulation the lab scale Mi-Pro high shear mixers with different bowl volumes could be used to determine the optimal process parameters and to scale up to the Collette Gral 10 pilot scale.

Lactose↗

PubMed2002

Development and in vitro evaluation of an enteric-coated multiparticulate drug delivery system for the administration of piroxicam to dogs.

The aim of the study was to develop enteric-coated pellets for the administration of piroxicam (a poorly water-soluble drug) to small animals in order to avoid local gastrointestinal irritation, one of the major side effects of nonsteroidal anti-inflammatory drugs after oral ingestion. Pellets were made by an extrusion-spheronization process. The influence of several excipients on the in vitro drug release was evaluated. Piroxicam release from the uncoated pellets was measured in phosphate buffer (pH 6.8) using the paddle dissolution method (USP XXIII). The enteric-coated pellets were tested in 0.1 N HCl and phosphate buffer, pH 6.8. The addition of sodium croscarmellose (Ac-Di-Sol) did not influence the piroxicam release from microcrystalline cellulose pellets. Sodium carboxymethyl starch (Explotab) increased the release from 30 to 65% at 45 min. The incorporation of sodium carboxymethyl cellulose on its own or as a co-processed blend with microcrystalline cellulose (Avicel RC 581 and CL 611) enhanced the release of piroxicam at 45 min from 30% (pure Avicel PH 101) to 95% (combination of Avicel PH 101 and CL 611 in a ratio of 1:3). Additional use of cyclodextrins had only a minor influence on the dissolution rate. An Eudragit L 30 D-55 and FS 30 D (6/4) film was applied to the core pellets (containing 2.5% (w/w) piroxicam and a combination of Avicel PH 101 and CL 611 in a ratio of 1:3) in order to obtain gastroresistant properties. The coated pellets retained their dissolution characteristics after compression into fast disintegrating tablets because waxy cushioning beads were added to minimize film damage.

Animals↗

PubMed2002

In vitro evaluation of the quality of essential drugs on the Tanzanian market.

We evaluated the in vitro availability and its stability under simulated tropical conditions of various formulations of four essential drugs marketed in Tanzania. We obtained 22 formulations (containing paracetamol, acetylsalicylic acid, chloroquine or sulphadoxine/pyrimethamine) from wholesale pharmacies in Dar es Salaam and the Medical Stores Department (Tanzania). The drug content, in vitro availability (dissolution) and its stability under simulated tropical conditions were determined using methods specified in the United States Pharmacopoeia (USP) 24 monograph of the respective drugs. All formulations passed the pharmacopoeia requirements for the drug content. However, seven formulations (three acetylsalicylic acid, two sulphadoxine/pyrimethamine and two paracetamol) failed to meet the USP 24 tolerance limits for dissolution. Another five formulations (three paracetamol and two chloroquine) failed to meet the dissolution tolerance limits after being subjected to an accelerated stability test under simulated tropical conditions (75% RH/40 degrees C) for 6 months. The study has demonstrated the presence on the Tanzanian market of essential drug formulations that met potency requirements and yet had unsatisfactory in vitro availability as they were not robust enough to withstand storage under simulated tropical conditions.

Drug Stability↗