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Biomedical subjects

F Kiekens

Publications and source records attributed to F Kiekens.

12 recordsLinked to original sources
PubMed2005

Tablets prepared by single-step granulation/tabletting: interparticulate binding mechanism and stability.

The binding mechanism of tablets prepared by single-step granulation/tabletting (SSGT), a novel technique for the production of tablets, was evaluated. SSGT yielded hard tablets having a short disintegration time due to their porous, spongelike internal structure. Calculation of the interaction factor and electrical conductance tests confirmed the presence of solid bridges that provided a higher tensile strength to these compacts in comparison to tablets prepared by conventional tabletting techniques. At high relative humidity, moisture sorption and glass-to-rubber transition of the binder (polyvinylpyrrolidone), or condensation of moisture on the internal pore surface, reduced the tensile strength of the SSGT-manufactured tablets. Contrary to tablets prepared by granulation and compression, the SSGT tablets did not harden during storage under conditions of varying relative humidity (alternating the relative humidity every 24 hr between 33% and 75%).

Drug Stability↗
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

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↗
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

Influence of drying temperature and granulation liquid viscosity on the inter- and intragranular drug migration in tray-dried granules and compacts.

The influence of the drying temperature and granulation liquid viscosity on the inter- and intragranular migration of a poorly water-soluble compound in a granulation mass and in a compact was quantitatively assessed. The intergranular migration kinetics were investigated by evaluating the drug distribution at different drying-time intervals. The results were analyzed by use of two-factor, three-level, face-centered, central composite designs. Riboflavin was mixed with alpha-lactose monohydrate 90 M and granulated with distilled water, except for the viscosity experiments in which an aqueous polyvinylpyrrolidone (PVP) (Kollidon K90) solution was used. The wet granules were dried in a hot-air oven or compacted prior to drying. The drug concentration at different locations inside the granulated mass and the compacts after drying was determined spectrophotometrically and by use of diffuse light reflectance measurements. The riboflavin distribution in the granulation masses and in the compacts was characterized by drug-enriched outer layers and drug-depleted inner regions, indicating a strong migration phenomenon. It was clear that the drying temperature had no influence on the inter- and intragranular drug distribution. The intergranular migration was avoided using the PVP as a binder in the granulation liquid, whereas a minimal granulation liquid viscosity of 100 mPa.sec was necessary to avoid the intragranular migration. The diffuse light reflectance measurements can be used for the in-process control of granule samples containing low drug concentrations without the destruction of the samples.

Hot Temperature↗
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

Evaluation of the emulsifying properties of some cationic starches.

Different cationic potato, maize, and waxy maize starches were evaluated for their emulsifying properties. Emulsions were prepared using 20% (w/w) arachidic oil and 80% (w/w) water. Emulsions with the cationic starches as emulsifier in a concentration ranging from 1% to 5% (w/w) were prepared and characterized by droplet size and viscosity measurements, and the stability was evaluated visually and by electrical conductance measurements. None of the cationic potato, waxy maize starches, and maize starches with a low degree of substitution (DS) showed adequate emulsifying properties. Emulsions prepared using non-pregelatinized (C [symbol: see text] bond 05914, 2% and 5% w/w; C [symbol: see text] bond 05907, 5% w/w) and pregelatinized (C [symbol: see text] bond 12504, 5% w/w) cationic maize starches with high-DS were visually stable. The initial mean droplet volume diameter of the emulsions prepared with these cationic starches in a 5% (w/w) concentration was similar and ranged from 2.40 to 2.84 microns; however, there was an important difference in droplet size distribution. The droplet size distribution of the emulsions prepared using the non-pregelatinized high-DS cationic starches was markedly narrower than in the case of the emulsions prepared using the pregelatinized high-DS cationic starches. The droplet size of the emulsions remained almost constant during 120 days of storage. Visual inspection and electrical conductance measurements showed that these emulsions were stable for at least 120 days.

Cations↗
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

[Evaluation of substrate-binder interfacial interactions].

Substrate-binder interfacial interactions were evaluated on the basis of the physico-chemical and mechanical properties of granules and compressed samples. Linear relationship was found between the breaking strength, the diffuse reflectance and the binder content of the examined granule-systems and compressed samples. The increasing amount of binder in the granules improved the adhesive interaction existing between the substrate and the binder. Our results indicate that the mechanical properties of the single particles as well as of the compressed samples were basically determined by the physico-chemical interactions of the substrate-binder interfacial layer. The qualitative and quantitative evaluation of these interactions has a decisive impact on the formulation and in process control of solid dosage forms of optimal mechanical properties.

Binding Sites↗
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↗