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Biomedical subjects

F Podczeck

Publications and source records attributed to F Podczeck.

At least 37 records · Page 2Linked to original sources
PubMed2001

The determination of fracture mechanics properties of pharmaceutical materials in mode III loading using an anti-clastic plate bending method.

Powder compacts made from acetylsalicylic acid and lactose monohydrate were subjected to an anti-clastic plate bending method in order to obtain the critical stress intensity factor in mode III loading (tearing or antiplane shear mode). The theoretical approach for data processing was based on linear elastic fracture mechanics. In contrast to mode I loading (opening or tensile mode), where above a critical threshold value the critical stress intensity factor is independent of the notch depth, i.e. converts into a true material constant, in mode III loading the critical stress intensity factor could only be presented under strict reference to a defined notch length. For lactose monohydrate, the typical exponential relationship between critical stress intensity factor and plate porosity was found. However, this was not the case for acetylsalicylic acid plates, indicating a change in fracture origin from pores and clusters of pores at higher porosities to machine flaws at low porosities. Hence, no extrapolation to zero porosity was attempted for this material, whereas for lactose monohydrate, the critical stress intensity factor at zero porosity was estimated to be 102+/-14 MNm(3/2). This value is valid for a notch depth of 4.9+/-0.3 mm. From the values obtained for the critical stress intensity factor and the critical strain energy release rate in mode III loading and an anisotropy ratio, here defined as the ratio between the critical stress intensity factors obtained in mode I and mode III loading, it was concluded that acetylsalicylic acid is the more brittle material and that lactose monohydrate behaved rather ductile under the given experimental conditions.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

The influence of type and quantity of model drug on the extrusion/spheronization of mixtures with microcrystalline cellulose. I. Extrusion parameters.

Five model drugs, (methyl, propyl and butyl paraben, 4-hydroxybenzoic acid and propyl gallate), similar in their chemical structure were mixed with microcrystalline cellulose and water in different proportions and forced through a ram extruder. The overall water movement was measured by the difference between the initial water in the formulation and the water content in the plug remaining after extrusion was completed. The differences in theoretical and practical volume occupancy of the materials inside the barrel were calculated to look for trapped air inside the barrel. The steady-state extrusion force for each formulation was recorded. All five materials demonstrated differences in behaviour during extrusion. The relationship between each of the three properties measured and both the drug-load and initial water content was examined, to establish the potential relationship that existed between the differences due to the drug models. The five drug models were divided into two sub-groups, when examining the way that they underwent extrusion. Methyl, propyl and butyl paraben formed one group while 4-hydroxybenzoic acid and propyl gallate formed the other group. Within the former group the relationship between steady-state extrusion force and the percentage of drug and water present tended to be lower than those in the latter group. For the former group these relationships were non-linear.

Antioxidants↗
PubMed2001

Use of a capillary rheometer to evaluate the rheological properties of microcrystalline cellulose and silicified microcrystalline cellulose wet masses.

The influence of microcrystalline cellulose (MCC) type and water content on the rheological properties of the wet powder masses were studied using two different MCC grades (Avicel and Emcocel) and silicified microcrystalline cellulose (SMCC, Prosolv). A ram extruder was used as a capillary rheometer and unique flow curves for each cellulose grade and moisture content were derived. In addition, the elastic parameters of recoverable shear and compliance were determined. From different flow curve models evaluated, it was not possible to obtain clear evidence, which model best described the rheological properties of each cellulose grade at each water level. Furthermore, the residuals were shear rate dependent, which indicates that the models do not perfectly agree with physical properties of the wet masses. The elastic properties of wet masses increased with increasing water content and decreased with increasing shear stresses. SMCC grade proved to be more elastic than the simple MCC grades at each moisture content. Thus, the rheological properties of MCC and SMCC wet masses were different and changed with water content. Consequently, it was not possible to achieve similar rheological properties between different grades of cellulose by altering the water content of the wet mass.

Cellulose↗
PubMed2001

The influence of formulation variables on the properties of pellets containing a self-emulsifying mixture.

A method of converting self-emulsifying drug delivery systems to a pellet form has been studied. Formulations with varied relative quantities of an oil/surfactant mixture, water, microcrystalline cellulose (MCC), and lactose were chosen in a statistical design after preliminary ranging experiments. Pellets were produced by extrusion/spheronization. The characteristics of the pellets were studied by sieving, disintegration testing, diametral compression, image analysis, non-contact laser profilometry, and scanning electron microscopy. The effects of the formulation variables on pellet properties were evaluated by analysis of variance. It was possible to relate the formulation variables to all the quantified pellet properties except the shape. The relative quantities of oil/surfactant and water had an effect on the amount of liquid and oil/surfactant that could be incorporated into the powder, extrusion force, median diameter, size spread, disintegration time, tensile strength, and surface roughness. The relative quantities of lactose and MCC had an effect on the amount of liquid and oil/surfactant that could be incorporated into the powder, tensile strength, and roughness only. Water was an essential element of the formulations. The maximum quantity of the specific oil/surfactant combination studied that can be incorporated was 42% of the dry pellet weight.

Drug Delivery Systems↗
PubMed2001

Measuring the water retention capacities (MRC) of different microcrystalline cellulose grades.

The ability of various types of microcrystalline cellulose (MCC) to hold water when subjected to an applied force has been assessed by a centrifuge technique. By considering the final percent of water retained after a standard centrifugation, as a function of the initial water content, a moisture retention capacity (MRC) can be determined. Statistical analysis of the results identified that it was possible to divide the nine samples of MCC into six sub-sets in terms of final moisture content retained. Those types which contained added polymer had by far the highest water level remaining. In terms of the MRC value, statistical analysis again sub-divided the celluloses into six sub-sets, although different from those for the final water content. Again those types containing added polymer gave much higher MRC values. As experiments were carried out with initial water/MCC ratios of different levels, statistical analysis of the influence of initial water content on the MRC values was undertaken with each type of MCC. The results showed a varying dependence on initial water level with the different types of cellulose. To provide a value of MRC which characterised the cellulose, the maximum value of MRC at the lowest initial water level was identified. Samples of MCC with low values of MRC have been shown previously to require less water for processing by extrusion/spheronization, while celluloses with a high MRC value appear better for the limitation of water movement during the process of extrusion/spheronization. The water retention must, however, also be considered in association with the rheological properties of the wet powder mass. Thus, while the Avicel RC591 had the highest MRC value, its rheological properties are so that the production of pellets with such a type can be less effective than with other types of MCC.

Algorithms↗
PubMed2001

Characterization of microcrystalline cellulose and silicified microcrystalline cellulose wet masses using a powder rheometer.

A powder rheometer has been used to study the properties of wet powder masses and the results have been compared to the mixer torque rheometer (MTR). Two different microcrystalline cellulose (MCC) grades (Avicel and Emcocel) and silicified microcrystalline cellulose (SMCC, Prosolv) were used as model powders. The wet massing behaviour of one material (Prosolv) was studied by the powder rheometer using liquid addition experiments, while the rheological properties of wet granules were studied using both the powder rheometer and the MTR. In water addition measurements the torque behaved in a similar way to MTR measurements and the maximum value of ZTL (zero torque limit) was achieved at the capillary state of wet mass. The wet granules exhibited different behaviour in the powder rheometer and the MTR experiments, which indicates that these rheometers involve different shear forces or they measure different properties of the wet granules. Emcocel wet masses achieved the capillary state at lower liquid amount than Avicel and Prosolv masses, which indicates that Emcocel is not able to hold as much water in the internal structure as Avicel and Prosolv. The powder rheometer proved to be a sensitive piece of equipment, which can be used to study both dry and wet powder masses. It was able to distinguish wet granules from wet powder masses after liquid addition, whereas the MTR could not. However, before the powder rheometer can be properly utilised in wet powder mass studies, the problem of torque overload requires resolution.

Cellulose↗
PubMed2001

The development of an instrumented tamp-filling capsule machine II. Investigations of plug development and tamping pressure at different filling stations.

A previously described [Eur. J. Pharm. Sci. 10 (2000) 267] pneumatic tamping head with attached instrumentation, capable of recording tamping forces generated on a Bosch GKF tamp-filling machine with high precision was employed to investigate the development and density of plugs during capsule tamp-filling of two soft, ductile powders. The study aimed to make a contribution to control capsule fill weight by monitoring the tamping force. The results indicated that the tamping station utilised to measure the tamping force and that involved in the regulation of the pressure of the pneumatic chamber of the tamping head should preferably not be the same. A possible solution would be to install the instrumented pneumatic tamping head on tamping station 4, after which in all cases plugs had formed to their maximum length and density. A second pneumatic tamping head, without instrumentation, could be installed on tamping station 3, which would receive signals from the instrumentation, and as a result the inner chamber pressure of this second pneumatic tamping head could be changed to adjust fill weight. The cumulative tamping distance should be large enough to produce a force reading well above the limit set by the inner chamber pressure, but small enough to avoid overfilling of the capsules. The latter can be detected monitoring the variability of the tamping forces recorded. A larger standard deviation of the tamping forces obtained from tamping station 4 was found to be a strong indicator of overfilling.

Capsules↗
PubMed2001

Preparation of pellets of different shape and their characterization.

Pellets of different shapes were produced by modifying the processing parameters of a standardized pellet formulation. The target size of these pellets was 1-1.4 mm. Initially the shape of the pellets was assessed by visual observation. In total, eight batches of pellets were produced of which four were considered to be round, whereas the other four deviated from the spherical shape by various degrees. The different pellet fractions were then characterized for their size, shape, surface, and density properties employing a series of established techniques in order to identify the most appropriate method of characterization and the interrelationships between these properties. The results showed that attempting a task of preparing pellets of graded differences in shape from the same powder blend can result in changes of other important pellet properties such as surface roughness, surface area, and pellet dimensions. Some of these changes could be anticipated by considering the process variables involved, whereas others changed in a manner for which there is no immediate explanation.

Microscopy, Electron, Scanning↗
PubMed2000

Development of a dual approach to assess powder flow from avalanching behavior.

The purposes of this investigation were to develop a method to evaluate flow properties of powders from avalanching tests and to detect similarities and relationships between these data and conventional powder flow properties. The API AeroFlow automated flowability analyzer was tested using 6 pharmaceutical excipients. Data were presented as mean time to avalanche (MTA), scatter, and a classification based on the type of motion of the powder bed. Powders were also characterized in terms of particle size, particle shape, loss of weight on drying, Carr's compressibility index, and critical orifice diameter to prevent ratholing. A dual approach, which combines visual observation of the type of motion of the powder bed in the rotating drum with numerical descriptors such as MTA and scatter, was found to be more accurate in the assessment of powder flow than the current practice of using only MTA and scatter values. Statistical analysis established that there are relationships and similarities between the ranking of powder flow properties obtained from the avalanching test and Carr's compressibility index and the critical orifice diameter. An interaction between particle size and shape, both influencing powder flow, when evaluated with these methods was found. The assessment of the flowability of powders on the basis of avalanching tests should include both the determination of numerical descriptors of flow such as MTA and scatter, and a determination of the type of motion of the powder bed in order to increase the sensitivity of the method to small changes in powder flow properties.

Aerosols↗
PubMed2000

The development of an instrumented tamp-filling capsule machine I. Instrumentation Of a Bosch GKF 400S machine and feasibility study.

The instrumentation of capsule filling machines operating by the tamp-filling principle has been described only once, using strain gauges. In the present paper the instrumentation of a Bosch GKF 400S tamp-filling machine has been described using a prototype of a pneumatic tamping head equipped with a piezoelectric force transducer. The pneumatic system replaces the conventional springs situated between tamping pins and upper part of the tamping head. Via a feedback switch valve, the air pressure inside the pneumatic chamber can be regulated. This provides a potential mechanism for feedback control of capsule fill weight during continuous capsule filling. It was found that the use of the pneumatic tamping head is limited to the control of fill weight during tamping. Major adjustments of fill weight at the set-up stage of the machine should be made by alteration of the tamping pin and powder bed height settings. The principles of capsule fill weight control by continuous monitoring of tamping forces have been established, but the transfer of the system to full industrial use requires further development of the prototype by the machine manufacturer.

Capsules↗
PubMed2000

Powder and capsule filling properties of lubricated granulated cellulose powder.

Granulated powdered cellulose was studied in terms of powder bulk properties and capsule filling performance on a tamp-filling machine with and without the addition of various concentrations of magnesium stearate. Carr's compressibility reached its minimum value at 0.4% magnesium stearate suggesting an improvement of powder flow compared to the unlubricated material. However, shear cell measurements and the use of a powder rheometer indicated that the addition of 0.2% magnesium stearate and more impairs powder flow and does not reduce interparticulate friction. When capsules were filled into hard gelatine capsules at a zero-compression setting, the fill weight and plug density could be predicted from Carr's compressibility index and from the maximum bulk density. The decrease in one and simultaneous increase in the other bulk property with increasing magnesium stearate concentration caused both fill weight and plug density to go through a minimum at a lubricant concentration of 0.4%. When the capsules were filled at maximum compression, however, the addition of lubricant increased the coefficient of fill weight variation significantly, and the plug density remained constant for any added concentration of magnesium stearate. These findings were in agreement with the shear cell and powder rheometer results. However, the optimum lubricant concentration in terms of ease of machine function, which was identified from tamping pressure measurements, was found to be 0.8% magnesium stearate, which was not an optimal concentration for the powder bulk properties.

Capsules↗
PubMed2000

The determination of the mechanical properties of elongated tablets of varying cross section.

The mechanical properties of elongated tablets of different thickness prepared at a range of pressures with surfaces that are flat or curved, have been determined by application of a flexure test. The strength of the tablets in terms of breaking load increases with an increase in the cross-sectional area of the tablets. To provide an improved method of comparing the strength of the tablets, the tensile strength of the specimens has been calculated from equations based on stress analysis. While an allowance for a change in thickness was provided by such a system there was a clear indication that the specimens tensile strength was still dependent on their dimensions. For equivalent central core thickness strength increased with the face curvature. This could be due to changes of the structure within the specimen during the formation process and there were clear indications that tablet porosities for equivalent compaction pressures were not equal. The differences could, however, be utilised to provide optimum conditions of curvature and central core thickness to give maximum tablet strength.

Chemistry, Pharmaceutical↗
PubMed2000

The shell dissolution of various empty hard capsules.

The shell dissolution properties of gelatine, gelatine/polyethylene glycol (PEG) and hydroxypropyl methylcellulose (HPMC) capsules were studied as a function of temperature, dissolution medium, and after different storage conditions. In any dissolution medium with a pH below or equal to 5.8, HPMC capsule shells dissolved rapidly, and there was no difference in the time in which dissolution occurred in the tested temperature interval of 10 to 55 degrees C. Gelatine and gelatine/PEG capsule shells, generally, did not dissolve at temperatures below 30 degrees C. The shell dissolution time of all capsules tested was prolonged and more variable in mixed phosphate buffer pH = 6.8. The addition of enzymes (pepsin, pancreatin) to any dissolution medium was found not to enhance the differences between the different types of capsules investigated. In practical terms, the results indicated that capsule formulations should not be taken with drinks from the carbonated Cola-type. Gelatine containing capsules should preferably be administered with a warm drink, whereas HPMC capsules could be given with cold or warm drinks. The latter type of capsules should also be preferred for preparations to be taken in the fasted state. A short storage of gelatine containing capsules under hot humid tropical conditions appeared not to alter the dissolution properties of the shells, and changes in disintegration times and dissolution times of formulations filled in such capsules might be a reflection of changes of the powders incorporated rather than of the capsule shells. However, a short storage of HPMC capsules under such conditions appeared to influence the capsule shell matrix.

Administration, Oral↗
PubMed1999

Evaluation of a standardised procedure to assess the shape of pellets using image analysis.

The influence of threshold definition, number of pellets counted, image magnification and lightning technique on the assessment of pellet shape has been investigated using three batches of pellets and an image analysis system. The pellet parameters measured were 'aspect ratio', 'circularity', 'projection sphericity', 'e(R)' and 'Feret diameter.' The methodical error, reproducibility and repeatability of the results were chosen as statistical test parameters. The position of the light source is crucial in providing an accurate particle size value. Top light was identified as the illumination technique that gave a mean pellet size similar to the true pellet size. The use of a light table produced significantly larger pellet size values. A minimum pixel resolution appears necessary for an accurate shape parameter definition. One pixel should not cover more than 30 microm for pellets of an average particle size of 1.2 mm. Shape descriptors, which are based on a multiple combination of area and perimeter data such as the circularity, are greatly dependent on the number of pellets counted. Shape factors, which do not (aspect ratio) or only as a single value do involve an area or perimeter measurement (e(R), projection sphericity) are, however, nearly independent of the number of pellets counted, as long as the magnification is sufficiently large and the pellets are randomly drawn from the batch. For nearly spherical particles, the methodical error is below 1%, but for elongated particles this error can reach 5%. The repeatability is also very good for nearly spherical particles (<2%), but increases to very large values if the particles are clearly elongated. The limiting values for the various shape factors should be reconsidered. An upper value for the aspect ratio of 1.1 and a lower value of 0.6 for e(R) are recommended. The circularity should not be used as the shape factor to characterise spheres, because errors in image recognition can affect strongly the applicability of this shape factor. The projection sphericity has only a limited sensitivity to variations in particle shape.

Chemistry, Pharmaceutical↗
PubMed1999

The filling of granules into hard gelatine capsules.

Four different granule size fractions of Sorbitol instant(R) were filled into hard gelatine capsules on a tamp filling (Bosch) and a dosator nozzle machine (Zanasi) to allow comparison of the filling principles. An acceptable filling performance was always achieved and was independent of the machine type employed. Tamp filling was found to be slightly better for the coarser granule size fractions, because it does not seem to rely on a firm plug formation. A direct relationship between the angle of internal flow (Varthalis and Pilpel, 1976) and the coefficient of fill weight variation was found for both systems. Using the dosator nozzle machine, the plug formed was always denser than the maximum bulk density, whereas on the tamp filling machine for smallest granule size the maximum plug density could not be achieved with the settings employed. The results suggest that in situations where a low plug density is an essential prerequisite for drug dissolution and bioavailability the tamp filling machine appears the more suitable filling principle. However, if a greater extent of compression is required in order to fill large dose drugs or to use a smaller capsule size, the dosator nozzle principle might work more successfully for granules.

Capsules↗
PubMed1999

Powder filling into hard gelatine capsules on a tamp filling machine.

A series of pharmaceutical excipient powders used in capsule formulations as fillers have been filled into hard gelatine capsules on a Bosch GKF-400S tamp filling machine. These machines depend on pushing pins through a powder bed so that a unit dose is transferred into a dosing disc. This dose is then ejected into the capsule body. The results indicate that the range of powders that can be filled on this type of machine exceeds that applicable to a dosator nozzle system. Filling problems due to powder flooding could be solved by increasing the powder bed height in the powder bowl. The fact that such powders usually do not form a firm plug was not reflected in the coefficient of fill weight variation, and uniform filling could hence be achieved without problems. The influence of the powder bed height on the capsule fill weight increased with decreasing powder flow. The influence of the setting of the tamping pins on the capsule fill weight was comparatively small and further decreased with a decrease in powder flow. However, when a granulated product (Elcema G250) was filled, the tamping pin setting was more important than the influence of the powder bed height on the capsule fill weight. For moderate flowing powders the coefficient of fill weight variation appeared to be nearly independent of powder bed height or tamping pin setting. However, the filling performance of powders with poor flow properties could be adjusted by optimising both machine settings. Very complex relationships were found between the powder properties such as angle of internal flow, dynamic densification profile, Carr's compressibility index and particle size and shape, and the filling behaviour.

Capsules↗
PubMed1999

Investigations into the reduction of powder adhesion to stainless steel surfaces by surface modification to aid capsule filling.

The adhesion force of powder particles to stainless steel surfaces, which had been modified by various metal coatings, has been measured using a centrifuge technique. The surfaces were characterised by surface roughness and surface free energy measurements, whereas the particles, which had a particle size of 32-45 microns, were characterised by their surface free energy only. The roughness of the surfaces was found to be similar, so that changes in the adhesion properties of the powders to these surfaces could not be due to a change in this surface property. However, there was a major difference in the surface free energy parameters of the surfaces. The surface free energy varied from a nearly non-polar character to strong Lewis-base. The adhesion force of pregelatinised starch and lactose monohydrate particles increased with the increasing base character of the surfaces. In principle this behaviour could also be seen for calcium carbonate particles. However, here the order of the adhesion forces to the surfaces tested was disrupted on one occasion because of a pronounced influence of particle and surface hardness on this property. In general, the ranking of the adhesion forces matched observations made during capsule filling on a Bosch GKF-400 tamp-filling machine. It was therefore concluded that a metal coating of the tamping pins would be able to reduce powder adhesion. In order to identify the best coating, centrifugal adhesion force measurements could be undertaken, or surface free energy measurements could be made. The results found suggest that a surface finish by means of chromium nitride coating provided, in most cases, a significant reduction of the powder adhesion. For very hard powder particles such as inorganic excipients the hardness of the surfaces must also be increased. In these cases plasma-coating of chromium appears helpful.

Capsules↗