32 research outputs found
Characterization of the coating and tablet core roughness by means of 3D optical coherence tomography
This study demonstrates the use of optical coherence tomography (OCT) to simultaneously characterize the roughness of the tablet core and coating of pharmaceutical tablets. OCT is a high resolution non-destructive and contactless imaging methodology to characterize structural properties of solid dosage forms. Besides measuring the coating thickness, it also facilitates the analysis of the tablet core and coating roughness. An automated data evaluation algorithm extracts information about coating thickness, as well as tablet core and coating roughness. Samples removed periodically from a pan coating process were investigated, on the basis of thickness and profile maps of the tablet core and coating computed from about 480,000 depth measurements (i.e., 3D data) per sample. This data enables the calculation of the root mean square deviation, the skewness and the kurtosis of the assessed profiles. Analyzing these roughness parameters revealed that, for the given coating formulation, small valleys in the tablet core are filled with coating, whereas coarse features of the tablet core are still visible on the final film-coated tablet. Moreover, the impact of the tablet core roughness on the coating thickness is analyzed by correlating the tablet core profile and the coating thickness map. The presented measurement method and processing could be in the future transferred to in-line OCT measurements, to investigate core and coating roughness during the production of film-coated tablets
At-line validation of optical coherence tomography as in-line/at-line coating thickness measurement method
Optical Coherence Tomography (OCT) is a promising technology for monitoring of pharmaceutical coating processes. However, the pharmaceutical development and manufacturing require a periodic validation of the sensor's accuracy. For this purpose, we propose polyethylene terephthalate (PET) films as a model system, to periodically validate the measurements during manufacturing. This study proposes a new approach addressing the method validation requirement in the pharmaceutical industry and presents results for complementary methods. The methods investigated include direct measurement of the layer thickness using a micrometer gauge as reference, X-ray micro computed tomography, transmission and reflectance terahertz pulsed imaging, as well as 1D- and 3D-OCT. To quantify the significance of OCT for pharmaceutical coatings, we compared the OCT results for commercial Thrombo ASS and Pantoloc tablets with direct measurements of coating thickness via light microscopy of microtome cuts. The results of both methods correlate very well, indicating high intra- and inter-tablet variations in the coating thickness for the commercial tablets. The light microscopy average measured coating thickness of Thrombo ASS (Pantoloc) was 71.0 µm (83.7 µm), with an inter-coating variability of 8.7 µm (6.5 µm) and an intra-coating variability of 2.3 µm to 9.4 µm (2.1 µm to 6.7 µm)
Predicting capsule fill weight from in-situ powder density measurements using terahertz reflection technology
The manufacturing of the majority of solid oral dosage forms is based on the densification of powder. A good understanding of the powder behavior is therefore essential to assure high quality drug products. This is particularly relevant for the capsule filling process, where the powder bulk density plays an important role in controlling the fill weight and weight variability of the final product. In this study we present a novel approach to quantitatively measure bulk density variations in a rotating container by means of terahertz reflection technology. The terahertz reflection probe was used to measure the powder density using an experimental setup that mimics a lab-scale capsule filling machine including a static sampling tool. Three different grades of α-lactose monohydrate excipients specially designed for inhalation application were systematically investigated at five compression stages. Relative densities predicted from terahertz reflection measurements were correlated to off-line weight measurements of the collected filled capsules. The predictions and the measured weights of the powder in the capsules were in excellent agreement, where the relative density measurements of Lactohale 200 showed the strongest correlation with the respective fill weight (R 2 =0.995). We also studied how the density uniformity of the powder bed was impacted by the dosing process and the subsequent filling of the holes (with excipient powder), which were introduced in the powder bed after the dosing step. Even though the holes seemed to be filled with new powder (by visual inspection), the relative density in these specific segments were found to clearly differ from the undisturbed powder bed state prior to dosing. The results demonstrate that it is feasible to analyze powder density variations in a rotating container by means of terahertz reflection measurements and to predict the fill weight of collected capsules
Crystal shape modification via cycles of growth and dissolution in a tubular crystallizer
Besides size and polymorphic form, crystal shape takes a central role in engineering advanced solid materials for pharmaceutical and chemical industry. This work demonstrates how multiple cycles of growth and dissolution can manipulate the habit of an acetylsalicylic acid crystal population. Considerable changes of the crystal habit could be achieved within minutes due to rapid cycling, i.e., up to 25 cycles within <10 min. The required fast heating and cooling rates were facilitated using a tubular reactor design allowing for superior temperature control. The face specific interactions between solvent and the crystals’ surface result in face specific growth and dissolution rates and hence alterations of the final shape of the crystals in solution. Accurate quantification of the crystal shapes was essential for this work, but is everything but easy. A commercial size and shape analyser had to be adapted to achieve required accuracy. Online size, and most important shape, analysis was achieved using an automated microscope equipped with a flow-through cell, in combination with a dedicated image analysis routine for particle tracking and shape analysis. Due to the implementation of this analyser, capable of obtaining statistics on the crystals’ shape while still in solution (no sampling and manipulation required), the dynamic behaviour of the size shape distribution could be studied. This enabled a detailed analysis of the solvent’s effect on the change in crystal habit
Influence of Particle Properties on the Yield and Selectivity of Fast Heterogeneously Catalyzed Gas-Liquid Reactions
Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS
Crystallization of the drug entacapone from binary solvent mixtures was monitored in situ using Raman optical probe. The recorded Raman spectra and statistical analysis, which included the principal components method and indirect hard modeling made it possible to estimate the starting point of crystallization, to assess crystallization temperatures and to provide information on the polymorphic content in the mixture. It was established that the crystallization temperatures were proportional to the volume content of the solvent in the mixtures. The samples were also evaluated off-line via Raman spectroscopy and SWAXS. The collected data showed the presence of forms β and γ in all solvent mixtures. In toluene/methanol 30:70 mixture, in addition to forms β and γ at least one of the forms A, D or α was also indicated by SWAXS. The results have shown that the presence of a particular polymorph is strongly dependent on the nature and portion of the solvent in the binary solvent mixture
Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS
Crystallization of the drug entacapone from binary solvent mixtures was monitored in situ using a Raman optical probe. The recorded Raman spectra and statistical analysis, which included the principal components method and indirect hard modeling made it possible to estimate the starting point of crystallization, to assess crystallization temperatures and to provide information on the polymorphic content of the mixture. It was established that crystallization temperatures were proportional to the volume content of the solvent in mixtures. The samples were also evaluated off-line via Raman spectroscopy and SWAXS. The collected data showed the presence of forms b and g in all solvent mixtures. In a toluene/methanol 30:70 mixture, in addition to forms b and g, at least one of the forms A, D or a was also indicated by SWAXS. The results have shown that the presence of a particular polymorph is strongly dependent on the nature and portion of the solvent in the binary solvent mixture