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Biomedical subjects

C Vervaet

Publications and source records attributed to C Vervaet.

18 recordsLinked to original sources
PubMed2002

In vivo evaluation of matrix pellets containing nanocrystalline ketoprofen.

The aim of this study was to evaluate the in-vivo behaviour of matrix pellets formulated with nanocrystalline ketoprofen after oral administration to dogs. No significant differences in AUC-values were seen between pellet formulations containing nanocrystalline or microcrystalline ketoprofen and a commercial ketoprofen formulation (reference: Rofenid 200 Long Acting). C(max) of the formulations containing nano- or microcrystalline ketoprofen was significantly higher compared to reference, whereas t(max) was significantly lower. The in-vivo burst release observed for the spray dried nanocrystalline ketoprofen matrix pellets was reduced following compression of the pellets in combination with placebo wax/starch pellets. These matrix tablets sustained the ketoprofen plasma concentrations during 5.6 and 5.4 h for formulations containing nano- and microcrystalline ketoprofen, respectively.

Administration, Oral↗
PubMed2002

Continuous twin screw extrusion for the wet granulation of lactose.

The suitability of continuous twin screw extrusion for the wet granulation of alpha-lactose monohydrate was studied and compared with conventional high shear granulation. The influence of process parameters (screw speed and total input rate) and formulation variables (water and polyvinylpyrrolidone (PVP) concentration) on the properties of granules (yield, particle size distribution, friability and compressibility) and tablets (tablet tensile strength, friability and disintegration time) was investigated. Variation of the formulation and process parameters had a major effect on the process feasibility. Optimization of these parameters is required to allow continuous processing and to ensure a high yield. Total input rate, screw speed and water concentration had a minor influence on the granule and the tablet properties. The addition of PVP had no major influence on the granule properties, but significantly affected the tablet characteristics. For granules formulated with and without PVP a yield above 50%, a friability below 30% and a compressibility below 15% was obtained. Tablets without PVP showed a tensile strength below 0.6 MPa, a friability above 1% and a disintegration time below 3 min, whereas tablets with PVP showed a tensile strength above 0.6 MPa, a friability below 1% and a disintegration time ranging from 8 to 15 min. High shear granulation was only possible when PVP was added and it required a higher amount of water. It was concluded that wet granulation of alpha-lactose monohydrate using continuous twin screw extrusion is a robust process and might offer a suitable alternative for high shear granulation in the pharmaceutical industry.

Algorithms↗
PubMed2002

Direct compression properties of melt-extruded isomalt.

Isomalt, a sugar alcohol, was melt-extruded prior to compression in order to improve its tabletting properties. After fusion, crystalline isomalt was transformed into an amorphous form as shown by X-ray diffraction and differential scanning calorimetry (DSC). The tabletting properties of amorphous isomalt were dramatically improved. Mixtures formulated with paracetamol (50%) and extruded isomalt yielded hard tablets. However, extruded isomalt powder showed agglomeration problems due to recrystallization of the amorphous phase into a stable crystalline form in the presence of atmospheric moisture. The evolution of the moisture content correlated well with the compressibility data. The tablets made of extruded isomalt powder had a lower friability in comparison to the tablets formulated with non-extruded isomalt powder. Their disintegration was fast and a rapid dissolution rate was recorded. Extruded isomalt displayed excellent tabletting properties; however, further experiments should be conducted to delay or even prevent recrystallization of amorphous isomalt.

Cariogenic Agents↗
PubMed2002

Direct compression and moulding properties of co-extruded isomalt/drug mixtures.

Isomalt, a disaccharide alcohol was co-extruded with paracetamol or hydrochlorothiazide (HCT) in order to improve its tabletting properties. After extrusion, isomalt was transformed into an amorphous form, while paracetamol remained crystalline. Hot stage microscopy showed that HCT was amorphous in the isomalt carrier up to a concentration of 1% (w/w). Direct compression of mixtures formulated with co-extruded isomalt/paracetamol powders yielded harder tablets compared with physical mixtures and no powder agglomeration was observed. Direct moulding of isomalt co-extruded with either paracetamol or HCT was feasible, yielding hard tablets. A fast dissolution rate was seen for both the compressed and the moulded tablets (>80% paracetamol and 60% HCT released within 20 min). The compressed tablets showed a dramatic decrease in tensile strength during storage at 85% RH, while the tensile strength of the moulded tablets remained above 0.80 MPa after 6 months storage at the same conditions. Co-extrusion of isomalt with paracetamol and HCT dramatically improved the tabletting properties of the mixtures (compared with physical mixtures of drug and isomalt). Direct moulding proved to be a suitable technique to produce isomalt based tablets.

Acetaminophen↗
PubMed2002

Principal component analysis of dissolution data with missing elements.

The use of principal component analysis (PCA) for incomplete dissolution data sets is examined. The PC space is constructed using a reference set and the test set is projected in that space. Several cases such as a reference set with missing data, an incomplete test set and both sets measured at different time points, are discussed using two examples: one simulation and one obtained from the pharmaceutical practice. From the many possibilities to deal with missing data, the expectation-maximization algorithm in combination with PCA was chosen. The influence on the similarity or f2 factor is examined too. The sampling with replacement or bootstrap technique, which can be used to obtain confidence limits, can also be used when missing data are present in one of the data sets.

Algorithms↗
PubMed2002

Characterization of ibuprofen as a nontraditional plasticizer of ethyl cellulose.

This study describes the characterization of the plasticizing properties of ibuprofen (IBP) on hot-melt extruded ethyl cellulose (EC). The thermal behavior of hot-melt extrudates containing 0, 5, 10, and 20% (w/w) IBP was evaluated using modulated temperature differential scanning calorimetry. By means of comparison, co-evaporates containing the same concentrations of IBP and EC, were also evaluated. Both methods yielded solid solutions having one glass transition temperature indicating compatibility between drug and polymer. A similar decrease in glass transition temperature was noticed with increasing IBP concentration in the solid solutions prepared via both methods, indicating its plasticizing effect. The plasticizing efficiency was of the same magnitude as for the traditionally used plasticizers. Infrared spectroscopy was performed for better understanding of the chemical interactions in the molecular dispersions and confirmed the existence of hydrogen bonds between IBP and EC. Overall, the study has highlighted the plasticizing properties of IBP on EC during hot-melt extrusion.

Cellulose↗
PubMed2001

Characterisation and disintegration properties of irradiated starch.

Irradiation treatment could provide a quick and simple way to modify the physical, chemical and pharmaceutical properties of biopolymers such as starch. Corn, potato and drum dried corn starch were exposed to X-ray and electron beam (e-beam) irradiation treatment at doses of 10, 50 and 100 kGy. The disintegration properties of these starches were compared using alpha-lactose monohydrate tablets containing 5% (w/w) starch as disintegrant. Starch solubility increased, while its swelling capacity decreased with increasing irradiation dose. The irradiation treatment caused fragmentation of the amylopectin fraction. Irradiation modified the different starches thoroughly, showing remarkable differences in disintegration properties after X-ray treatment and e-beam modification. The e-beam modification resulted in significantly higher disintegration times of the tablets.

Molecular Weight↗
PubMed2001

An oral controlled release matrix pellet formulation containing nanocrystalline ketoprofen.

A controlled release pellet formulation using a NanoCrystal colloidal dispersion of ketoprofen was developed. In order to be able to process the aqueous NanoCrystal colloidal dispersion into a hydrophobic solid dosage form a spray drying procedure was used. The in vitro dissolution profiles of wax based pellets loaded with nanocrystalline ketoprofen are compared with the profiles of wax based pellets loaded with microcrystalline ketoprofen and of a commercial sustained release ketoprofen formulation. Pellets were produced using a melt pelletisation technique. All pellet formulations were composed of a mixture of microcrystalline wax and starch derivatives. The starch derivatives used were waxy maltodextrin and drum dried corn starch. Varying the concentration of drum dried corn starch increased the release rate of ketoprofen but the ketoprofen recovery remained problematic. To increase the dissolution yield surfactants were utilised. The surfactants were either added during the production process of the NanoCrystal colloidal dispersion (sodium laurylsulphate) or during the pellet manufacturing process (Cremophor RH 40). Both methods resulted in a sustained but complete release of nanocrystalline ketoprofen from the matrix pellet formulations.

Administration, Oral↗
PubMed2001

Cold extrusion as a continuous single-step granulation and tabletting process.

The potential of cold extrusion as a continuous granulation/tabletting technique was investigated. Extrudates (X, 9 mm) were produced using twin-screw extrusion, cut manually into tablets (thickness, 4 mm) and dried at 25 degrees C for 20 h. alpha-Lactose monohydrate (200 M) was used as an excipient, PVP (Kollidon K30) and water as binders, and hydrochlorothiazide as the model drug. The influence of formulation (water content, PVP addition, drug incorporation) and process (total input rate and screw speed) parameters on the process (torque, die pressure, visual evaluation of tablets) and on the tablet properties (tensile strength, friability, disintegration time, porosity) was evaluated. Formulation, as well as process parameters, affected the process feasibility, but had only a minor effect on the tablet properties at conditions that allowed continuous tablet production. All alpha-lactose monohydrate tablets formulated without and with PVP and produced at optimum conditions showed tensile strengths above 0.7 and 1.5 MPa, friabilities below 1.0 and 0.9%, and disintegration times below 1 and 8 min, respectively. This technique allows single-step granulation/tabletting of pure alpha-lactose monohydrate, indicating that cold extrusion could be used as alternative tablet production technique for ingredients with poor compaction properties. As the tablets prepared by extrusion have a much higher porosity compared with conventional tablets, this technique could also be useful for tablet production of formulations with poor disintegrating properties.

Chemistry, Pharmaceutical↗
PubMed2000

Bioavailability of ibuprofen from matrix mini-tablets based on a mixture of starch and microcrystalline wax.

The bioavailability of ibuprofen from matrix mini-tablets based on microcrystalline wax and a starch derivative was tested. An oral dose of 300 mg of ibuprofen was administered to healthy volunteers (n=8) in a randomized cross-over study design either as a commercial matrix formulation (Ibu-Slow 600) or as mini-tablets (filled into hard gelatin capsules). The mini-tablets consisted of 60% ibuprofen, 15% Paracera M (wax), 22.5% DDWM (starch) and 2.5% triacetin (lubricant). t50% of the in vitro release was 4.5 and 5 h for the mini-tablet and Ibu-slow formulations, respectively. Both formulations behaved in vivo as sustained-release formulation; their HVDt50%Cmax value was determined at 5.6 and 5.1 h for the mini-tablet and Ibu-slow formulations, respectively. A significantly higher value of Cmax was seen for the mini-tablet formulation, resulting in a relative bioavailability of 116 +/- 22.6% compared to the Ibu-slow matrix. These data demonstrate that the experimental mini-tablets can be used to formulate sustained-release dosage forms.

Adult↗
PubMed2000

A validated HPLC method for the determination of thiazinamium methylsulphate in pharmaceutical preparations.

The phenothiazine derivative thiazinamium methylsulphate is a drug with antihistaminic and anticholinergic properties, often used in some types of obstructive lung diseases. Because there is a lack of chromatographic data available for its determination, the objective of the present investigation was to develop a sensitive and rapid HPLC method for the quantitative estimation of thiazinamium methylsulphate in a pharmaceutical dosage form, applicable to routine analysis. The drug was chromatographed on a C18-reversed phase system applying a Licrocart column (LiChrospher 100 RP 18, 125 x 4 mm) with a mobile phase consisting of acetonitrile-water (3:7, v/v), employing as ion-pairing agent octanesulphonic acid sodium salt (20 mM) together with N,N-dimethyloctylamine (20 mM), adjusted to pH 3. Detection occurred at 254 nm. Propylparaben was used as an internal standard. The method was applied to solutions for intramuscular injection containing thiazinamium methylsulphate (65 mg/2 ml). Since little sample preparation is required, most analyses can be carried out within 15 min. The optimized method was validated and provided acceptable results with respect to linearity (r = 0.9999), precision and accuracy in the concentration range of 26-78 microg/ml. The proposed method is presently employed to investigate the stability of thiazinamium methylsulphate in solutions for intramuscular injection in the presence of anti-oxidizing agents.

Chromatography, High Pressure Liquid↗
PubMed2000

Matrix mini-tablets based on starch/microcrystalline wax mixtures.

Matrix mini-tablets based on a combination of microcrystalline waxes and starch derivatives were prepared using ibuprofen as a model drug. The production of mini-tablets was preferred over the production of pellets, as up-scaling of the pelletisation process seemed problematic. Prior to tabletting, melt granulation in a hot stage screw extruder and milling were required. The in vitro drug release was varied using microcrystalline waxes with a different melting range, the slowest drug release being obtained with a formulation containing a microcrystalline wax with a melting range between 68 and 72 degrees C. Generally speaking increasing the wax concentration resulted in a slower drug release. In vitro drug release profiles were also modified using different starches and mixtures of starches. Increasing the ibuprofen concentration to 70% resulted in a faster drug release rate.

Capsules↗
PubMed2000

Polystyrene microsphere spray standards based on CFC-free inhaler technology.

Metered pressurized sprays were formulated containing polystyrene microspheres (PSM) suspended in 5% w/w ethanol in 1,1,1,2-tetrafluoroethane (HFA 134a). Suspensions with defined number concentrations, packaged in pressure-resistant glass containers, and fitted with specified 50-microL metering values and actuators were sonicated and fired (as if they were metered dose inhalers or MDIs). Following propellant evaporation, PSM dispersions in air containing > 98% singlets resulted from actuation of 3, 5, and 8 microns PSM suspensions containing 0.00125% w/w 3 microns, 0.05% w/w 5 microns or 0.3% w/w 8 microns PSMs, respectively. Spray characteristics from these systems depended on PSM concentration, PSM size, PSM source, and actuator dimensions. Adhesion of suspended PSMs to the internal glass surfaces of the containers were easily reversed by sonication but not prevented by a wide range of surfactants. Over a period of 6 months storage, these formulations produced reproducible PSM aerosols with known aerodynamic properties useful for calibration purposes.

Aerosols↗
PubMed1999

Characterization and evaluation of isomalt performance in direct compression.

Isomalt is a sugar substitute with a wide range of potential pharmaceutical applications as a result of its physicochemical properties. Four grades of this material were evaluated for their physical characteristics. Only Palatinit(R) C and F exhibited potential characteristics for direct compression. As expected, the products required lubrification for tabletting. A level of 1% lubricant gave the best performance for Palatinit(R) C, the most compressible grade as shown by compaction profiles generated using a single-punch machine. However, its flow behaviour had to be improved by including 0.5% Aerosil(R) 200 as shown by tablet weight uniformity data. Further evaluation by Heckel analysis showed that isomalt exhibited plastic behaviour and underwent elastic recovery primary in the die. Its dilution potential was examined using powdered paracetamol. Acceptable tablets were produced up to 30% drug dilution, but the tensile strength values were reduced, disintegration time and friability increased as expected. Drug dissolution profiles showed a decreasing dissolution rate with the increase of compression force and drug concentration, but considerable improvement was noted when a disintegrant was included. The physical characteristics of the tablets were relatively stable after half a year storage at different humidities as a result of the low hygroscopicity of isomalt.

Cariogenic Agents↗
PubMed1999

Pharmacokinetics of florfenicol after treatment of pigs with single oral or intramuscular doses or with medicated feed for three days.

The pharmacokinetics of florfenicol, a structural analogue of thiamphenicol, were studied in six pigs after single oral and intramuscular doses of 15 mg/kg bodyweight, and after feeding them with medicated feed containing 250 mg/kg for three days, a concentration which provided approximately the same dose rate of the drug. The oral doses contained a specially prepared pelleted formulation of the drug. The bioavailability of the drug was similar for the oral and intramuscular doses. Florfenicol was absorbed rapidly from the feed and its concentration in plasma remained between 2 and 6 microg/ml - above the minimum inhibitory concentration values for common pig pathogens - during the three days.

Administration, Oral↗
PubMed1999

Drug-surfactant-propellant interactions in HFA-formulations.

The required replacement of chlorofluorocarbon (CFC) with hydrofluoroalkane (HFA) propellants has challenged formulators of pressurized metered dose inhalers in several major respects. Conventional (CFC soluble) surfactants are effectively insoluble in the major CFC replacement candidates, HFA 134 and HFA 227ea, in the absence of co-solvents. While these ethane and propane derivatives have comparable boiling points and vapor pressures to dichlorodifluoromethane (CFC 12), their increased polarity demands that formulators use either alternative (soluble) surfactants, or co-solvents along with traditional surfactants, in order to stabilize pressurized suspension products. The use of either approach is complicated by the existence of many competing patents and the fact that the science in the area is empirical; predictive theoretical approaches are frustrated by the lack of an adequate database. Technical developments in this area must also take into account the need to avoid crystal growth and/or adhesion of micronized, suspended drugs to internal container surfaces, problems which may be catalyzed by some combinations of surfactant type/concentration, vehicle(s) and physical form/type(s) of drug substance. For some drugs, it appears simpler to use co-solvents with HFA propellants to dissolve the drug, avoiding the need for suspension stabilization. This article presents an overview of the present state of the art with respect to the formulation of MDIs.

Aerosols↗
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↗