Biomedical subjects

Torben Schaefer

Publications and source records attributed to Torben Schaefer.

12 recordsLinked to original sources

PubMed2006

The apparent plasticizing effect of polyethylene glycol (PEG) on the crystallinity of spray dried lactose/PEG composites.

Aqueous solutions of lactose and polyethylene glycol (PEG) were spray dried in a Büchi Model 191 spray dryer with the aim to investigate the effect of PEG on the crystallinity of the composite. A PEG concentration of 10.7% by weight of solids was studied for PEG 200, 600, 1500, 4000 and 8000. For PEG 200 and 4000 additional concentrations from 1.5-19.3% to 1.5-32.4%, respectively, were investigated. The spray dried composites were analysed with X-ray powder diffraction and modulating differential scanning calorimetry. The crystallinity of lactose in the composites varied from 0% to 60%, dependent on the molecular weight and concentration of PEG. Apparently, lactose crystallinity is promoted by low molecular weight and high concentration of the PEG. PEG did not affect the lactose glass transition temperature. It is suggested that lactose and PEG are solidified separately during spray drying and that partial crystallization of lactose is associated with effects of PEG on the rate of drying.

Calorimetry, Differential Scanning↗

PubMed2005

Effect of a melt agglomeration process on agglomerates containing solid dispersions.

The purpose was to produce solid dispersions of a poorly water-soluble drug, Lu-X, by melt agglomeration in a laboratory scale rotary processor. The effect of binder type and method of manufacturing on the dissolution profile of Lu-X was investigated. Lactose monohydrate and Lu-X were melt agglomerated with Rylo MG12, Gelucire 50/13, PEG 3000, or poloxamer 188. Either a mixture of binder, drug, and excipient was heated to a temperature above the melting point of the binder (melt-in procedure) or a dispersion of drug in molten binder was sprayed on the heated excipient (spray-on procedure). The agglomerates were characterized by DSC, XRPD, SEM, and EDX-SEM. The study showed that the agglomerates containing solid dispersions had improved dissolution rates compared to physical mixtures and pure drug. The melt-in procedure gave a higher dissolution rate than the spray-on procedure with PEG 3000, poloxamer 188, and Gelucire 50/13, whereas the opposite was found with Rylo MG12. This was explained by differences in mechanisms of agglomerate formation and growth, which were dominated by immersion with PEG 3000, poloxamer 188, and Gelucire 50/13, and by distribution and coalescence with Rylo MG12. The spray-on procedure resulted in a higher content of Lu-X in the core of the agglomerates when immersion was the dominating mechanism, and in a higher content in the agglomerate surface when distribution was dominating. The melt-in procedure resulted generally in a homogeneous distribution of Lu-X in the agglomerates. The compounds in the agglomerates were found primarily to be crystalline, and the dissolution profiles were unchanged after 12 weeks storage at 25 degrees C at 50% RH.

Calorimetry, Differential Scanning↗

PubMed2005

Agglomerate formation and growth mechanisms during melt agglomeration in a rotary processor.

The purpose of this study was to investigate the effect of the binder particle size and the binder addition method on the mechanisms of agglomerate formation and growth during melt agglomeration in a laboratory scale rotary processor. Lactose monohydrate was agglomerated with molten polyethylene glycol (PEG) 3000 by adding the PEG either as solid particles from the size fraction 0-250, 250-500, or 500-750 microm or as droplets with a median size of 25, 48, or 69 microm. It was found that the PEG particle size, the PEG droplet size, and the massing time significantly influenced the agglomerate size and size distribution. Agglomerate formation and growth were found to occur primarily by distribution and coalescence for the PEG size fraction 0-250 microm and mainly by the immersion mechanism for the PEG size fractions 250-500 and 500-750 microm. When the PEG was sprayed upon the lactose, the mechanism of agglomerate formation was supposed to be a mixture of immersion and distribution, and the agglomerate growth was found to occur by coalescence regardless of the PEG mean droplet size. Compared to high shear mixers and conventional fluid bed granulators, the mechanisms of agglomerate formation and growth in the rotary processor resembled mostly those seen in the fluid bed granulator.

Drug Compounding↗

PubMed2004

Melt pelletization with polyethylene glycol in a rotary processor.

The purpose of this study was to investigate the effect of the airflow, the binder concentration, the massing time, the friction plate rotation speed, and the surface structure of the friction plate on melt pelletization in a laboratory scale rotary processor. Lactose monohydrate was melt agglomerated with polyethylene glycol (PEG) 3000 as meltable binder. The study was performed as a full factorial design. An increase in agglomerate size was found when the binder concentration, the massing time, or the friction plate rotation speed was increased. The agglomerate size was also increased when increasing the shearing forces by using a friction plate with a different surface structure. The size distribution of the agglomerates was significantly narrowed when the binder concentration or the shearing forces caused by the friction plate were increased. An increase in the adhesion of material to the friction plate was found when the shearing forces of the friction plate were increased either by the rotation speed or by the surface structure. Generally, the rotary processor was found to be a suitable alternative to melt pelletization in a high shear mixer.

Adhesiveness↗

PubMed2004

Comparison of torque measurements and near-infrared spectroscopy in characterization of a wet granulation process.

The purpose of this study was to compare impeller torque measurements and near-infrared (NIR) spectroscopy in the characterization of the water addition phase of a wet granulation process. Additionally, the effect of hydrate formation during granulation on the impeller torque was investigated. Anhydrous theophylline, alpha-lactose monohydrate, and microcrystalline cellulose (MCC) were used as materials for the study. The materials and mixtures of them were granulated using purified water in a small-scale high-shear mixer. The impeller torque was registered and NIR spectra of wet samples were recorded at-line. The torque and the NIR baseline-corrected water absorbances increased with increasing water content. A plateau in the NIR baseline-corrected water absorbances was observed for wet masses containing MCC. This was at the region of optimal water amount for granulation according to the torque results. In the case of anhydrous theophylline, the slope of baseline-corrected water absorbance values increased at the same water amount as the impeller torque started to increase. The hydrate formation of theophylline during granulation was observed as a slight decrease in the impeller torque. In addition, the hydrate formation during granulation affected the granulation liquid requirement. The liquid requirement was different for monohydrate formed during granulation compared to one formed in high relative humidity before the granulation. The results suggest that NIR spectroscopy may be applicable to process monitoring of wet granulation, also in cases where monitoring of impeller torque is difficult to apply.

Spectroscopy, Near-Infrared↗

PubMed2004

Effects of powder particle size and binder viscosity on intergranular and intragranular particle size heterogeneity during high shear granulation.

A study was performed in order to elucidate the effects of powder particle size and binder viscosity on intergranular and intragranular particle size heterogeneities. Granules were produced by melt granulation in a high shear mixer from each of four calcium carbonates having mean particle sizes in the range of 5.5-63.1 microm. Each of three polyethylene glycols (PEGs) having viscosities in the range of approximately 40-14,000 mPas were applied as meltable binders. The size distribution of the calcium carbonate particles in three granule size fractions (125-250, 355-500, and 800-1000 microm) was measured after disintegration of the granules. Intragranular particle size heterogeneities were evaluated qualitatively by means of scanning electron microscopy. A preferential growth of the smaller particles was found to give rise to a higher content of small particles in large granules when calcium carbonates with mean particle sizes of 11.7, 34.5, and 63.1 microm were granulated with a binder of low viscosity. The use of a binder of medium or high viscosity leads to a marked reduction of these heterogeneities. A preferential growth of larger particles was seen when calcium carbonates with mean particle sizes of 5.5 and 11.7 microm were granulated with a highly viscous binder. The use of a binder with low or medium viscosity resulted in an increased homogeneity. Intragranular particle size heterogeneities were primarily seen when 5.5 and 11.7 microm calcium carbonate particles were granulated with a highly viscous binder.

Excipients↗

PubMed2004

Design and atomization properties for an inside-out type effervescent atomizer.

Atomization of aqueous polymer solutions is a key step in the formulation of several pharmaceutical products. Droplet size control is essential in order to produce pharmaceutical products with the desired properties. The purpose of this paper is to investigate design issues for an inside-out type of effervescent atomizer used to spray water and aqueous solutions of polyvinylpyrrolidone (Kollidon K-30) and hydroxypropyl methylcellulose (Pharmacoat 603). The atomizer was operated at air-to-liquid mass ratios of 0.1, 0.3, and 0.5 and a feed pressure of 1172 kPa. Fluid viscosities ranged from 1 to 47 mPa.s. The influence of several atomizer design features was considered, including exit orifice length-to-diameter ratio, exit orifice diameter, the total area of the air injection holes, the distance between the air injection point and the exit orifice, the diameter of the mixing chamber, and the orientation of both air and liquid flows. Droplet size distributions were shown to vary significantly with the atomizer's exit orifice diameter, air injector design, and air injector distance to the exit orifice. In all cases air-to-liquid mass ratio played a key role in the mean droplet size. The design of the atomizer was shown to have the most pronounced effect on the mean droplet size at the lowest air-to-liquid mass ratios. Optimization of the atomizer design is very important in order to obtain small droplet sizes in pharmaceutical processes where the amount of air/gas should be minimized, e.g., closed-cycle spray drying and agglomeration processes.

Chemical Phenomena↗

PubMed2004

Particle formation and capture during spray drying of inhalable particles.

An investigation of the spray drying process is made in great detail regarding particle formation and capture efficiency with focus on the production of inhalable particles. Mannitol was spray dried as model substance and the spray-dried products were characterized. The resulting products consisted of smooth spheres with a volume median diameter of 2.2-5.5 microm, and narrow size distributions. The investigation was performed in pilot scale of sufficient size to draw general conclusions and make some recommendations. It has been shown that the size of particles is decreased when the feed concentration is decreased, the nozzle gas/feed flow mass ratio increased, and the droplet size decreased. The collection efficiency of the cyclone device used in this study was shown to have a cut-off of 2 microm, i.e., 50% of the particles less than 2 microm are not captured. The data reported indicate that the majority of the single particles formed here, <5 microm, arise from single droplets (of about 10 microm) and are solid, nonporous particles.

Administration, Inhalation↗

PubMed2003

The preparation of agglomerates containing solid dispersions of diazepam by melt agglomeration in a high shear mixer.

The aim of this study was to prepare by melt agglomeration agglomerates containing solid dispersions of diazepam as poorly water-soluble model drug in order to evaluate the possibility of improving the dissolution rate. Lactose monohydrate was melt agglomerated with polyethylene glycol (PEG) 3000 or Gelucire 50/13 (mixture of glycerides and PEG esters of fatty acids) as meltable binders in a high shear mixer. The binders were added either as a mixture of melted binder and diazepam by a pump-on procedure or by a melt-in procedure of solid binder particles. Different drug concentrations, maximum manufacturing temperatures, and cooling rates were investigated. It was found to be possible to increase the dissolution rate of diazepam by melt agglomeration. A higher dissolution rate was obtained with a lower drug concentration. Admixing the binders by the melt-in procedure resulted in similar dissolution rates as the pump-on procedure. The different maximum manufacturing temperatures and cooling rates were found to have complex effects on the dissolution rate for formulations containing PEG 3000, whereas only minor effects of the cooling procedure were found with Gelucire 50/13. Gelucire 50/13 resulted in faster dissolution rates compared to PEG 3000.

Diazepam↗

PubMed2002

The effect of droplet size and powder particle size on the mechanisms of nucleation and growth in fluid bed melt agglomeration.

This study was performed in order to evaluate the effects of binder droplet size and powder particle size on agglomerate formation and growth in fluid bed spray agglomeration using a meltable binder. Three different lactose grades, 100, 125 or 350 mesh, were agglomerated using polyethylene glycol (PEG) 3000 at two different concentrations, 11.5 or 22% (volume/mass), and three spray droplet sizes, 30, 60 or 90 microm were applied. The ratio of droplet size/particle size was found to determine whether the mechanism of nucleation was distribution or immersion. Distribution was promoted by a low ratio, whereas immersion was promoted by a high ratio. Distribution as nucleation mechanism led to a more open agglomerate structure and immersion to a denser structure. When the nucleation phase was terminated, coalescence between rewetted nuclei or agglomerates was the growth mechanism with both preceding mechanisms of nucleation. A larger particle size of the lactose led to larger agglomerates. The difference in the effect on growth between the 30 and 60 microm droplets was generally low. The 90 microm droplets at 22% binder concentration offered a potential for uncontrollable growth giving rise to markedly larger agglomerates and a lower reproducibility than 30 and 60 microm droplets.

Particle Size↗

PubMed2002

Effects of droplet size and type of binder on the agglomerate growth mechanisms by melt agglomeration in a fluidised bed.

This study was performed in order to evaluate the effects of binder droplet size and type of binder on the agglomerate growth mechanisms by melt agglomeration in a fluidised bed granulator. Lactose monohydrate was agglomerated with melted polyethylene glycol (PEG) 3000 or Gelucire 50/13 (esters of polyethylene glycol and glycerol), which was atomised at different nozzle air flow rates giving rise to median droplet sizes of 40, 60, and 80 microm. Different product temperatures were investigated, below the melting range, in the middle of the melting range, and above the melting range for each binder. The agglomerates were found to be formed by initial nucleation of lactose particles immersed in the melted binder droplets. Agglomerate growth occurred by coalescence between nuclei followed by coalescence between agglomerates. Complex effects of binder droplet size and type of binder were seen at low product temperatures. Low product temperatures resulted in smaller agglomerate sizes, because the agglomerate growth was counteracted by very high binder viscosity or solidification of the binder. At higher product temperatures, neither the binder droplet size nor the type of binder had a clear effect on the final agglomerate size.

Fats↗

PubMed2002

Development of fast-disintegrating pellets in a rotary processor.

The aim of the present work was to formulate fast-disintegrating pellets by direct pelletization in a rotary processor. Formulations containing kaolin or bentonite and lactose were agglomerated with or without the addition of crospovidone in an instrumented rotary processor. The effects of the excipients on the amount of wall adhesion, the size and size distribution, the disintegration time, and the shape of the agglomerates, as well as the content of agglomerates > 2800 microns, were investigated. Further, pellets containing a model drug having a low aqueous solubility were prepared, and the drug dissolution profile was compared to that of pellets containing microcrystalline cellulose (MCC). Formulations containing kaolin resulted in fast-disintegrating pellets. Pellets containing bentonite eroded, but did not disintegrate, and the formulations gave rise to large amounts of wall adhesion. The addition of crospovidone increased the water content at the end of liquid addition for all formulations, and resulted in slightly more spherical agglomerates. When comparing formulations containing kaolin and MCC, kaolin gave rise to wider size distributions and a higher amount of agglomerates > 2800 microns, but the drug dissolution rate was much faster. Complete (100%) drug release was seen after 8 min with the kaolin formulation, whereas only 40% was released after 2 hr from the MCC formulation.

Bentonite↗