Biomedical subjects

Katharina M Picker

Publications and source records attributed to Katharina M Picker.

7 recordsLinked to original sources

PubMed2004

The 3D model: explaining densification and deformation mechanisms by using 3D parameter plots.

The aim of the study was to analyze very differently deforming materials using 3D parameter plots and consequently to gain deeper insights into the densification and deformation process described with the 3D model in order to define an ideal tableting excipient. The excipients used were dicalcium phosphate dihydrate (DCPD), sodium chloride (NaCl), microcrystalline cellulose (MCC), xylitol, mannitol, alpha-lactose monohydrate, maltose, hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (NaCMC), cellulose acetate (CAC), maize starch, potato starch, pregelatinized starch, and maltodextrine. All of the materials were tableted to graded maximum relative densities (rhorel, max) using an eccentric tableting machine. The data which resulted, namely force, displacement, and time, were analyzed by the application of 3D modeling. Different particle size fractions of DCPD, CAC, and MCC were analyzed in addition. Brittle deforming materials such as DCPD exhibited a completely different 3D parameter plot, with low time plasticity, d, and low pressure plasticity, e, and a strong decrease in omega values when densification increased, in contrast to the plastically deforming MCC, which had much higher d, e, and omega values. e and omega values changed only slightly when densification increased for MCC. NaCl showed less of a decrease in omega values than DCPD did, and the d and e values were between those of MCC and DCPD. The sugar alcohols, xylitol and mannitol, behaved in a similar fashion to sodium chloride. This is also valid for the crystalline sugars, alpha-lactose monohydrate, and maltose. However, the sugars are more brittle than the sugar alcohols. The cellulose derivatives, HPMC, NaCMC, and CAC, are as plastic as MCC, however, their elasticity depends on substitution indicated by lower (more elastic) or higher (less elastic) omega values. The native starches, maize starch and potato starch, are very elastic, and pregelatinized starch and maltodextrine are less elastic and exhibited higher omega values. Deformation behavior as shown in 3D parameter plots depends on particle size for polymers such as CAC and MCC; however, it does not depend on particle size for brittle materials such as DCPD. An ideally deforming tableting excipient should exhibit high e, d, and omega values with a constant ratio of e and omega at increasing densification.

Excipients↗

PubMed2004

"Soft tableting": a new concept to tablet pressure-sensitive materials.

The aim of this study was to confirm the hypothesis that tableting using excipients with greater elastic deformation results in improved performance of pressure-sensitive drugs relative to the excipients with low elastic deformation. Tableting with highly elastic deforming excipients and the resultant minimization of the process damage is referred to in this article as "soft tableting." Carrageenans, chitosans, and polyethylene oxides were tested as potentially useful tableting excipients. alpha-Amylase, amorphous indomethacin, theophylline monohydrate, and enteric-coated pellets were used as models for pressure-sensitive materials. Three-dimensional modeling of the tableting data and elastic recovery of the tablets were the tools for mechanical characterization. The crushing force of the tablets was analyzed. Inactivation of alpha-amylase was determined by using the starch iodine reaction method. Pseudopolymorphic and polymorphic changes were analyzed using Fourier transform (FT) Raman spectroscopy. The effects of pressure on the integrity of the pellets were tested by release studies and scanning electron microscopy. The process of tablet formation was characterized for potentially useful tableting excipients. The results were compared with the results of traditional excipients as microcrystalline cellulose (MCC), dicalcium phosphate dihydrate, and hydroxypropyl methylcellulose (HPMC). A ranking order for soft tableting was deduced from the mechanical properties. The tableting excipients were ranked according to their general plasticity (GP): GP(carrageenans)<GP(chitosans)<GP(MCC)<GP(HPMC)<GP(polyethylene oxides). This theoretical order of suitability has been experimentally proven to be valid for the pressure-sensitive materials. In conclusion, the new concept for soft tableting is valid.

Chemistry, Pharmaceutical↗

PubMed2003

The 3-D model: does time plasticity represent the influence of tableting speed?

The objective of this study is to test the hypothesis that time plasticity (parameter d from 3-D modeling) is influenced by tableting speed. Tablets were produced at different maximum relative densities (rho(rel, max)) on an instrumented eccentric tableting machine and on a linear rotary tableting machine replicator. Some 3-D data plots were prepared using pressure, normalized time, and porosity according to Heckel. After fitting of a twisted plane, the resulting parameters were analyzed in a 3-D parameter plot. The materials used were dicalcium phosphate dihydrate (DCPD), spray-dried lactose, microcrystalline cellulose (MCC), hydroxypropyl methylcellulose (HPMC), kappa-carrageenan (CAR), and theophylline monohydrate (TheoM). The results show that tableting speed especially influences the parameter d (time plasticity) of the 3-D model for plastically and viscoelastically deforming materials such as MCC, HPMC, CAR, and TheoM. For more plastically deforming materials such as MCC, HPMC, and TheoM, a subtle influence on omega is also visible. The stages of higher densification are affected more than the stages of lower densification. Brittle materials such as DCPD exhibit no influence of tableting speed. The influence of speed on spray-dried lactose is minor. The results are valid for data obtained from an eccentric tableting machine and also for data from a linear rotary tableting machine replicator. Thus, the empirically derived parameter time plasticity d really represents the influence of time.

Chemistry, Pharmaceutical↗

PubMed2003

Potential of carrageenans to protect drugs from polymorphic transformation.

Carrageenans were analysed in mixture with polymorphic drugs to test their potential for minimising polymorphic or pseudopolymorphic transitions, which are induced by the tableting process. The kappa-carrageenans Gelcarin GP-812 NF and Gelcarin GP-911 NF and the iota-carrageenan Gelcarin GP-379 NF were tested in comparison to the well-known tableting excipients microcrystalline cellulose (MCC), hydroxypropyl methylcellulose (HPMC), and dicalcium phosphate dihydrate (DCPD). Amorphous indomethacin was chosen as model drug since its well-known recrystallisation behaviour can be mechanically stimulated. Further on, theophylline monohydrate was used. Its dehydration is induced by tableting. Pure materials and mixtures containing 20% (w/w) drug were compressed up to different maximum relative densities. The data obtained during tableting were analysed by three-dimensional (3D) modelling. Afterwards tablets were broken and examined by Fourier transform Raman spectroscopy in order to determine the degree of transformation inside the tablet. For quantitative interpretation, the intensities of representative bands were used. Thermal analysis was used additionally. Using 3D modelling a decrease of plastic deformation can be noticed in the order HPMC>MCC>carrageenans, whereas DCPD represents an exception because of brittle fracture. Best hindrance of polymorphic transformation showed the carrageenans, the hindrance was slightly worse for HPMC. MCC and DCPD could not hinder transformation. A complete protection of the amorphous form could not be achieved. For theophylline monohydrate, the results were similar.

Carrageenan↗

PubMed2003

The 3-D model: comparison of parameters obtained from and by simulating different tableting machines.

The aim of this study is to apply 3-D modeling to data obtained from different tableting machines and for different compression wheels on a linear rotary tableting machine replicator. A new analysis technique to interpret these data by 3-D parameter plots is presented. Tablets were produced on an instrumented eccentric tableting machine and on a linear rotary tableting machine replicator. The materials used were dicalcium phosphate dihydrate (DCPD), spray-dried lactose, microcrystalline cellulose (MCC), hydroxypropyl methylcellulose (HPMC), and theophylline monohydrate. Tableting was performed to different maximum relative densities (rho (rel, max)). Force, time, and displacement were recorded during compaction. The 3-D data plots were prepared using pressure, normalized time, and porosity according to Heckel. A twisted plane was fitted to these data according to the 3-D modeling technique. The resulting parameters were analyzed in a 3-D parameter plot. The results show that the 3-D modeling technique can be applied to compaction cycles from different tableting machines as different as eccentric and rotary tableting machines (simulated). The relation of the data to each other is the same even when the absolute values are different. This is also true for different compression wheels used on the linear rotary tableting machine replicator. By using compression wheels of different sizes on this simulator, mainly time plasticity changes. By using bigger compression wheels for simulation, the materials deform slower at lower densification and they deform faster at higher densification. For brittle materials, the stages of higher densification are influenced; for plastically deforming materials, the stages of lower and higher densification can be influenced.

Computer Simulation↗

PubMed2002

Characterization of the thermal properties of microcrystalline cellulose by modulated temperature differential scanning calorimetry.

The purpose of this study was to characterize the thermal properties of microcrystalline cellulose (MCC) and to investigate the influence of water on these properties. Differential scanning calorimetry (DSC), modulated temperature differential scanning calorimetry (MTDSC), thermomechanical analysis (TMA), and scanning electron microscopy (SEM) were used to characterize MCC. Three reproducible step transitions were detected in the dry material at 132, 159, and 184 degrees C; for these transitions the magnitude of the heat capacity change varied by a factor of two. Exposure of MCC to water lowers the transition temperature in a manner comparable to a glass transition. The effect of water was different for samples equilibrated to different atmospheric humidities versus water added by granulation. A change in the physical properties of MCC after granulation with high amounts of water was observed. In conclusion, it appears that MCC has glass transitions, which come in reproducible triplets, and these transitions are affected by the presence of water. Also, for the materials studied, the transition temperatures are not affected by particle size and pulp source.

Calorimetry, Differential Scanning↗

PubMed2002

Influence of tableting on the enzymatic activity of different alpha-amylases using various excipients.

The purpose of the study was to show the influence of compression pressure on the enzymatic activity of different types of alpha-amylases and to analyze the loss of activity of alpha-amylase in mixtures with different excipients. Following that, the properties of excipients used for tableting enzymes were evaluated. Tablets were produced on an instrumented single punch tableting machine. The pure amylases were tableted with increasing graded compaction pressures. Mixtures were tableted to different maximum relative densities, rho(rel,max). The remaining enzymatic activity of the alpha-amylase in the tablets was determined by the starch iodine reaction. The results show a difference between different types of alpha-amylase depending on their origin and additives. Enzymatic inactivation occurs for the pure materials at all pressures used. It is initiated during and continues after compaction. It can be inhibited by freezing the tablets. Another possibility is to tablet the enzyme in a mixture with excipients, which prevent inactivation by softly embedding the enzyme. One example which even stabilizes alpha-amylase at high volume reduction is kappa-carrageenan. In conclusion, enzymatic inactivation can be markedly reduced when excipients are used for tableting, which require little compaction pressure and are able to release the mechanical stress in the form of expansion.

Carrageenan↗