Biomedical subjects

C Vervaet

Publications and source records attributed to C Vervaet.

At least 19 recordsLinked to original sources

PubMed2003

Drug formulations intended for the global market should be tested for stability under tropical climatic conditions.

RATIONALE OBJECTIVE: The quality of drugs imported into developing countries having a tropical climate may be adversely affected if their formulations have not been optimized for stability under these conditions. The present study investigated the influence of tropical climate conditions (class IV: 40 degrees C, 75% relative humidity) on the drug content, in vitro dissolution and oral bioavailability of different formulations of two essential drugs marketed in Tanzania: diclofenac sodium and ciprofloxacin tablets. METHODS: Before and after 3 and 6 months storage under class IV conditions the drug content and in vitro dissolution were evaluated using United States Pharmacopoeia (USP) 24 methods. Following a randomized four-period cross-over study, the pharmacokinetic parameters of drug formulations stored for 3 months under class IV conditions were compared with those stored at ambient conditions. RESULTS: Drug content and drug release from all tested ciprofloxacin formulations were within USP-24 requirements and remained stable during storage at simulated tropical conditions. Oral bioavailability was also not influenced by tropical conditions. The dissolution rate of two diclofenac formulations (Diclo 50 manufactured by Camden and Dicloflame 50 manufactured by Intas) reduced significantly during storage under class IV conditions. After oral administration Camden tablets stored for 3 months under class IV conditions showed a reduction in C(max) (90% CI of C(max) ratio: 0.59 - 0.76). This reduction was smaller than expected based on the in vitro tests. CONCLUSIONS: Some drug formulations imported into Tanzania are not optimized for stability in a tropical climate. Manufacturers and regulatory authorities should pay more attention to the WHO recommendations for testing the stability of drugs under tropical climate conditions. Efforts should be made to improve the in vitro tests to better predict the bioavailability.

Administration, Oral↗

PubMed2003

Development and evaluation of sustained release mini-matrices prepared via hot melt extrusion.

Sustained release mini-matrices (multiple unit dosage form) were developed by means of hot-melt extrusion using ibuprofen as the model drug and ethyl cellulose as sustained release agent. Ibuprofen release from the ibuprofen-ethyl cellulose matrices (60:40 w/w) was too slow (20% in 24 h). Other excipientia (hydroxypropyl methylcellulose and xanthan gum) were added to the formulation to increase the drug release. Changing the viscosity and substitution type of HPMC, the amount of HPMC, the drug load and the HPMC:EC ratio modified the in vitro drug release. Burst release was noticed for the formulations containing HPMC and a nearly time independent drug release was seen for the xanthan gum based mini-matrices. Drug release from the mini-matrices was mainly diffusion controlled and swelling played an important role to obtain complete drug release. The formulations were at least 12 months stable during storage at 60% RH and room temperature. At a higher relative humidity and temperature the drug release increased.

Delayed-Action Preparations↗

PubMed2002

Bioavailability of hydrochlorothiazide from isomalt-based moulded tablets.

The bioavailability of hydrochlorothiazide (HCT) from moulded isomalt-based tablets was evaluated after oral administration of 50 mg HCT to healthy volunteers as an oral moulded tablet and as a lozenge, in comparison with a conventional tablet formulation (Dichlotride 50 mg). Moulded tablets had a high relative bioavailability (F(rel)) as the pharmacokinetic parameters (C(max), t(max), t(1/2), AUC(0-->24 h)) determined from HCT plasma concentration versus time profiles were not significantly different (P>0.05; two-way ANOVA) in comparison with the conventional tablet. The relative bioavailability of the moulded tablet administered as a lozenge and as an oral tablet was 106.2+/-30.9% and 89.4+/-25.9%, respectively, in relation to the conventional tablet formulation. Direct moulding of isomalt tablets proved to be a suitable technique to administer a poorly soluble drug either as a conventional tablet or as a lozenge.

Administration, Oral↗

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↗

PubMed2002

Wax beads as cushioning agents during the compression of coated diltiazem pellets.

Placebo particles were mixed with film-coated diltiazem pellets to evaluate them as cushioning agents during tabletting in order to protect the film coat from damage. The cushioning properties of alpha-lactose monohydrate granules, microcrystalline cellulose pellets and wax/starch beads were evaluated by comparing the dissolution profile of the coated pellets before and after compression (compression force 10 kN). Only the tablet formulations containing wax/starch beads provided protection to the film coat. However, the dissolution rate of tablets formulated with waxy maltodextrin/paraffinic wax placebo beads was too slow as the tablets did not disintegrate. Adding 50% (w/w) drum-dried corn starch/Explotab/paraffinic wax beads to the formulation was the optimal amount of cushioning beads to provide sufficient protection for the film coat and yield disintegrating tablets. Using a compression simulator, the effect of precompression force and compression time on the dissolution rate was found to be insignificant. The diametral crushing strength of tablets containing 50% (w/w) drum-dried corn starch/Explotab/paraffinic wax beads was about 25.0 N (+/-0.3 N), with a friability of 0.4% (+/-0.04%). This study demonstrates that adding deformable wax pellets minimizes the damage to film-coated pellets during compression.

Compressive Strength↗

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↗