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Biomedical subjects

P Kleinebudde

Publications and source records attributed to P Kleinebudde.

At least 19 recordsLinked to original sources
PubMed2005

Interaction of water with different cellulose ethers: a Raman spectroscopy and environmental scanning electron microscopy study.

Different non-ionic cellulose ethers like methyl cellulose (MC), hydroxypropyl cellulose (HPC) and hydroxypropylmethyl cellulose (HPMC) were investigated. The characterization of the cellulose ethers was carried out by thermogravimetry and sorption/desorption isotherms. Differences in the properties of the cellulose ether films were described by time-dependent contact angle measurements. Changes in molecular structure of the raw materials, gels and films caused by water contact were studied using Raman spectroscopy. Differences between the substitution types and changes due to the gel or film formation were observed. An environmental scanning electron microscopy (ESEM) technique was used to distinguish the morphological behaviour of the cellulose ether films in contact with water. Based on in-situ ESEM experiments, the swelling and drying behaviour of the various stages of cellulose ether films (film-hydrated film-dried film) were quantified by using image analysis.

Absorption↗
PubMed2002

Polymer erosion in PLGA microparticles produced by phase separation method.

This article deals with polymer erosion in biodegradable microparticles produced using the phase separation method. Poly(lactic-co-glycolic acid) copolymers with different compositions and molecular weights were employed. The microparticles were stored in phosphate buffer for 6 months. The molecular weight of the polymers was determined by size exclusion chromatography, and the weight loss was monitored gravimetrically. No weight loss was measured in the first weeks, although the molecular weight decreased significantly already from the start. After a certain storage period which was found to be specific for the type of polymer, the weight of the microparticles decreased rapidly. The start of this weight loss occurred when the molecular weight of the polymer in the degrading microparticles reached a threshold of approximately 15,000. This critical molecular weight was found to be identical for all investigated polymers, i.e. it was independent of the initial molecular weight of the polymer and of the lactic-glycolic ratio.

Chromatography, Gel↗
PubMed2001

Extrusion/spheronization of pectin-based formulations. II. Effect of additive concentration in the granulation liquid.

PURPOSE: The aim of this study was to improve the formation of spherical pectin pellets by investigating the effect of additive concentration in the granulation liquid on the shape and size of the products as well as by identifying an optimal additive concentration. METHODS: High-methoxylated, low-methoxylated, and amidated low-methoxylated pectin types were evaluated in combination with different concentrations of methanol, ethanol, citric acid, lactic acid, and calcium chloride. Pellets were prepared in a power-consumption-controlled twin-screw extruder, then spheronized and dried. The moisture content of the extrudate was determined, and the final products were characterized by image analysis and sieving analysis. A cloud point test was employed for the identification of an optimal additive concentration. RESULTS: The concentration of additive in the granulation liquid affected the moisture content of the extrudate and the shape, size, and mechanical stability of the pectin pellets. Improvements in the pellet characteristics are dependent on the pectin type employed. The 2 low-methoxylated pectins were more sensitive to concentration changes than was the high-methoxylated type. Above a certain threshold concentration, the quality of the pellets are improved. This additive concentration differs according to type of pectin and type of additive. CONCLUSION: It was demonstrated that there is a concentration-dependent interaction between pectin and substances added to the granulation liquid that can be utilized to improve the formation of spherical pectin pellets.

Calcium Chloride↗
PubMed2001

Extrusion/spheronization of pectin-based formulations. I. Screening of important factors.

This study investigated the possibility of producing pectin-based pellets by extrusion/spheronization. The study also identified factors influencing the process and the characteristics of the resulting product. Three types of pectin with different degrees of amid and methoxyl substitution were studied in combination with different granulation liquids (water, calcium chloride, citric acid, and ethanol) and/or microcrystalline cellulose. Pellets were prepared in a power-consumption-controlled, twin-screw extruder; then they were spheronized and dried. The products were characterized by image analysis, sieving analysis, and disintegration and dissolution tests. The results were evaluated by multivariate analysis. Different additives, either in the granulation liquid or in the powder mixture, influenced the ability of the extruded mass to form pellets (the processability) with this technique. However, the various pectin types responded to modifications to a different extent. Short, nearly spherical pellets are obtained with granulation liquids, such as ethanol, that reduce the swelling ability of pectin. Pellets produced with ethanol are, however, mechanically weak and tend to disintegrate. Pectin molecules with a high degree of free carboxylic acid groups seem to be more sensitive to changes in the granulation liquid. Addition of microcrystalline cellulose as an extrusion aid generally resulted in improvements in shape and size. It was demonstrated that the processability of pectin as well as the characteristics of the products can be influenced in different ways during the process (eg, adding substances to the granulation liquid or to the powder mixture).

Cellulose↗
PubMed2001

A simple method for evaluating the mixing efficiency of a new type of pan coater.

The objective of this study was to investigate some important process parameters on the mixing behavior of a new coater type. The coater used in this study, the Bohle BLC pan coater, differs from other coaters in its high length to diameter ratio. The pan coater can be divided into two zones: drying and spraying zone. The temperature difference between two points in the pan (one in each zone) was used to explore the influence of some process parameters, i.e. the pan speed and the inclination of the rotation axis on the mixing behavior. In addition, the effect of the spray rate on the temperature difference was studied. The results of the current study demonstrated the possibility to characterize the mixing behavior in a pan coater by a simple temperature measurement. The temperature difference method resulted in a model, which was comparable to the model from a conventional mixture experiment. It was shown that the pan speed and the spray rate influenced the temperature difference and, consequently, the mixing efficiency. However, the inclination of the rotation axis did not show an important effect.

Drug Compounding↗
PubMed2001

Raman spectroscopic surface characterization of cellulose derivatives.

First results of experiments on the surface characterization of cellulose derivatives are presented. Different water contents of the surface of microcrystalline cellulose have been investigated by means of Raman spectroscopy, SERS, and environmental scanning electron microscopy (ESEM).

Journal Article↗
PubMed2001

Melt pelletization of a hygroscopic drug in a high shear mixer. Part 3. Effects of binder variation.

Melt pelletization experiments with sodium valproate as a hygroscopic drug were performed in a laboratory scale high shear mixer. In the current part, the effect of altering the binder liquid properties (using different binders, varying the temperature, or adding highly dispersed silicon dioxide to the molten binder) on the pellet size, size distribution and the growth rate was studied. Three meltable binders, namely glycerol monostearate (GMS), hydrated castor oil (HCO), and polyethylene glycol (PEG), were included in the study. Two series of experiments with GMS or HCO showed a higher granule growth rate with decreasing binder viscosity. Also, increases in the granule growth rate were observed for all meltable binders tested, when the binder amount and the impeller speed were increased. Factorial designs with all three binders were performed under the same conditions. In these experiments, no correlation existed between the granule growth rate and the viscosity of the different binders. The different granule growth rate, however, was mainly attributed to the different solubility of sodium valproate in the binder liquid used. Higher solubility increased the volume of the binder liquid and, accordingly, the granule growth rate. Taking the amount of dissolved drug into account, the granule growth rates of GMS and PEG were comparable. However, HCO displayed a lower granule growth rate, which might be related to its low adhesion tension. During melt pelletization in a high shear mixer the solubility of the drug in the molten binder strongly influences the pelletization process.

Silicon Dioxide↗
PubMed2000

Melt pelletisation of a hygroscopic drug in a high shear mixer. Part 2. Mutual compensation of influence variables.

The process of melt pelletisation in a Diosna P10 high shear mixer was examined for sodium valproate and glycerol monostearate. The effects of binder concentration, impeller speed and massing time on mean granule size, size distribution and liquid saturation were investigated. Spherical pellets of almost similar size and size distribution were obtained after 20 min of massing time, with a binder content from 3.1 to 14.1% w/w by adjusting the impeller speed. Granule growth was observed at low levels of binder concentration and liquid saturation (<80%) which is untypical for melt granulation. The liquid saturation seemed to have no major influence on the final pellet size. Additional, mutually compensating effects on granule growth were found to be impeller speed and massing time for a fixed binder concentration. Low levels of both, binder concentration and impeller speed, allowed for good control of the process. The amount of water adsorbed by the hygroscopic drug was found to accelerate granule growth.

Absorption↗
PubMed2000

Direct pelletization in a rotary processor controlled by torque measurements. I. Influence of process variables.

The aim of this study was to elucidate the feasibility of using torque measurement to control the end point of a wet pelletization process in a rotary processor at varying levels of friction plate rotation speed, air gap pressure difference, and batch size. A 1:1 mixture of lactose monohydrate (200 mesh) and microcrystalline cellulose (PH-101) was granulated into pellets in an instrumented laboratory scale rotary processor using water as aqueous binder liquid. A full factorial designed study was performed to investigate the influence of the friction plate rotation speed (600 and 1200 rpm), the air gap pressure difference (1 and 3 kPa), the torque increase (0.4 and 0.8 N.m) and the batch size (500 and 1000 g) on the pellet properties. All pellets produced were round and showed a narrow size distribution. The geometric mean diameter varied from 400 to 1900 microns with a good reproducibility. Increasing the batch size and the rotation speed led to smaller pellets, whereas a higher torque produced larger pellets. This study showed that the process can be controlled by means of the torque increase because it was possible to produce pellets of a reproducible size by stopping the liquid addition at a certain torque level.

Drug Compounding↗
PubMed2000

Influence of the degree of polymerization on the behavior of cellulose during homogenization and extrusion/spheronization.

The study objective was to investigate the influence of the degree of polymerization (DP) of cellulose materials (microcrystalline cellulose [MCC] and powder cellulose [PC]) on the behavior of these materials during homogenization and extrusion/spheronization processes. Suspensions of the cellulose types with different DP values were homogenized using a high-pressure homogenizer. The particle size, agglomeration index, and apparent viscosity of these suspensions was determined at different times after pouring. Additionally, these different cellulose types were processed into pellets using the extrusion/spheronization method, and the water content and power consumption as a function of the DP were determined. Cellulose types with a high DP value showed greater particle size after homogenization than the types with a low DP value. In contrast, no relevant relationship between the apparent viscosity and DP could be observed. During the extrusion process, water content in the extrudate and pellet porosity were increased as the DP was increased for the extrudates produced at the same level of power consumption. MCC types with various DPs compared with PC provided a novel way of understanding the role of cellulose in the extrusion process. The DP showed a remarkable influence on the physicochemical properties of the cellulose materials and, consequently, on the behavior of these materials during the extrusion/spheronization process. It is postulated that the sponge model is more appropriate for the cellulose type with high DP (PC), whereas the gel model is more applicable to cellulose types with lower DP (MCC).

Cellulose↗
PubMed2000

Direct pelletization in a rotary processor controlled by torque measurements. II: effects of changes in the content of microcrystalline cellulose.

In the present study we investigated the effect of changes in the content of microcrystalline cellulose (MCC) on a direct pelletization process in a rotary processor in which the liquid addition was terminated once a certain increase in torque was produced. Nine different mixtures of MCC and lactose with MCC contents varying from 10% to 100% (w/w) were pelletized using 6 different torque increase levels, and the changes in pellet characteristics were investigated. The pellet characteristics investigated were pellet shape, size, and size distribution as well as the water content of the pellets at the end of liquid addition. To produce spherical agglomerates with suitable characteristics in a reproducible way, a content of at least 20% (w/w) MCC was found necessary. Linear correlations were found between the MCC content and the water content and between the torque increase and the water content, showing that the torque increase is suitable to control the process. A higher torque increase or a higher MCC content was found to increase the water content independently of each other.

Cellulose↗
PubMed1999

Melt pelletisation of a hygroscopic drug in a high shear mixer. Part 1. Influence of process variables.

The applicability of a high shear mixer for melt pelletisation of binary mixtures of sodium valproate and glycerol monostearate was investigated. The effects of binder concentration, impeller speed, jacket temperature and massing time on mean pellet size and size distribution were examined in a 2(4)-factorial design. Binder concentration and impeller speed were found to be the most important variables influencing the mean granule size and size distribution. An increase in each of those accelerated the granule growth. Due to the solubility of the drug in the molten binder very low amounts of binder were necessary for the formation of pellets. The modified high shear mixer was found to be suitable for batch sizes of 1-4 kg; granule growth was delayed with increasing load. A common pellet growth pattern, which can be divided into three phases, was derived and confirmed from all trials. The process was monitored by means of a torque measuring system. The torque-time curve can be used to detect the beginning of the destruction phase.

Chemistry, Pharmaceutical↗
PubMed1999

Importance of the fraction of microcrystalline cellulose and spheronization speed on the properties of extruded pellets made from binary mixtures.

The aim of the study was to prove the importance of the binary mixture composition and spheronization speed on pellet properties. Extrudates from different binary mixtures of microcrystalline cellulose (MCC) and dicalcium phosphate dihydrate were prepared with a power-consumption-controlled extruder and spheronized at different speeds. The water content of the extrudate for the production of spherical pellets was evaluated. The pellets were characterized in terms of size, shape, porosity, mechanical properties, and disintegration. The fraction of MCC in the binary mixtures had the highest impact on the pellet properties. With an increasing fraction of MCC more water was required for successful pelletization, size and porosity of the pellets decreased, and the surface tensile stress increased. These observations were evaluated using the "sponge" and the "crystallite--gel" models for MCC. The latter led to the conception that an extrudate consists of two phases: a percolating crystallite--gel phase formed by MCC and water during extrusion and a filler phase formed by the second component of the binary mixture. This two-phase concept provides explanations for the extent of shrinking during drying and for the disintegration behavior. The spheronization speed had an influence on the size but not on porosity or surface tensile stress of the pellets. The best results were obtained at intermediate spheronization velocities of 10 and 13.4 m/sec. Fundamental properties of extrudates and pellets can be described by applying a two-phase concept of the crystallite--gel model.

Algorithms↗
PubMed1998

Comparison between a twin-screw extruder and a rotary ring die press. Part II: influence of process variables.

The influence of different processing steps on pellet quality was investigated: granulation/extrusion and spheronization. Pellets were produced at two levels of water content on two different types of extruders: a twin screw extruder and a rotary ring die press. In order to control the spheronization process each extrudate was rounded in two spheronizers using two radial velocities, respectively. Pellet shape and size were selected to describe the pellet quality. Under constant spheronization conditions the extrudates behaved dissimilar on the two spheronizers. This could be attributed to the geometry of the friction plates. The spheronizer with the rougher surface applied more mechanical energy to the extrudate and wet pellets which reduced the water content necessary for the formation of good pellets. Eliminating the influence of the spheronization process, high differences were observed in the quality of the extrudates produced by the two extruders. This confirmed the results from the first part of this study. Due to the crystallite-gel-model the different extruder types apply different mechanical stress on the extrudate which affect the network structure of the microcrystalline cellulose gel. The twin-screw extruder produced a more delicate network with a lower water movement. This led to a shift of the optimal moisture content towards higher values. Compared with spheronization, process changes in the granulation/extrusion process were more critical.

Chemistry, Pharmaceutical↗
PubMed1998

Mixture experiments with the oil phase of parenteral emulsions.

The effects of the oil phase as a mixture (binary, ternary) on the emulsion droplet size were investigated. The binary trials were performed with the aid of simplex lattice design with constraints. Droplet diameter was evaluated in terms of the oil phase viscosity and the interfacial tension between oil phase and the aqueous phase. As a result it could be shown that increasing the oil phase viscosity as a function of castor oil concentration led to a greater increase in particle size. At the same time, decreasing the interfacial tension of the oil phase as a function of oleic acid or oleic alcohol was shown to have a negligible effect on the particle size of the dispersed phase. A further aim was to find out a formulation by using a ternary oil phase resulting in a stable emulsion which could pass the autoclaving process. It was ascertained that oleic acid as a part of the oil phase led to proper formulation showing a satisfactory stability.

Castor Oil↗
PubMed1997

Residual solvents in biodegradable microparticles. Influence of process parameters on the residual solvent in microparticles produced by the aerosol solvent extraction system (ASES) process.

Different batches of microparticles were produced by the aerosol solvent extraction system (ASES) utilizing the extraction properties of supercritical carbon dioxide. Using a central composite design, the influence of production conditions such as spraying rate of the polymer solution and pump rate of the circulating carbon dioxide phase, on the characteristics of microparticles was studied. The experiments were carried out with regard to the residual solvent in the particles, the residual methylene chloride in the carbon dioxide flow of the ASES, the particle size, the morphology, and the yield. The results showed an influence of the pump rate of carbon dioxide on the yield, on the residual solvent in the microparticles, and on the circulating carbon dioxide. There was no major influence of the production conditions on the size and morphology of the microparticles, indicating that the ASES process seems to be a precipitation process.

Aerosols↗
PubMed1997

The crystallite-gel-model for microcrystalline cellulose in wet-granulation, extrusion, and spheronization.

PURPOSE: A new model for the wet-extrusion/spheronization process with microcrystalline cellulose (MCC) is proposed. The crystallite-gel-model is able to elucidate the unique role of MCC in this process. Many other experimental results, which cannot be explained by the standard model of granulation, the liquid saturation model, give evidence for the crystallite-gel-model. METHODS: Pellets were prepared from different types of MCC. Water content during extrusion, power consumption and aspect ratio were correlated. X-ray diffractograms of MCC powders, extrudates and pellets were taken in order to provide information on changes at the single crystallite level. SEM-photographs and leaching studies gave additional information on changes at the particulate level of MCC. RESULTS: At the level of MCC powder particles, dramatic changes occurred during extrusion/spheronization. In contrast to this no changes could be observed at the level of individual crystallites. CONCLUSIONS: During granulation and extrusion MCC-particles are thought to be broken down into smaller particles and possibly ultimate single crystallites in the presence of water. The crystallite-gel-model serves as the framework for a new interpretation of the wet-extrusion/spheronization process. Apart from the ability to explain experimental data published previously in the literature it can be used to develop new experimental plans for further research. Consequently, the crystallite-gel-model exhibits explanatory as well as predictive power.

Cellulose↗