Applicability of image analysis to support QbD driven development of pellets.

OBJECTIVE: The stages of preparing high drug loaded pellets were investigated using static and dynamic imaging techniques to provide a greater understanding and ease the scale up process. SIGNIFICANCE: An example of a real case laboratory and production scale quality by design (QbD) based development of pellets is demonstrated. Potential process analytical technology (PAT) approaches by dynamic image analysis (DIA) are presented in various process phases. METHODS: Pellets were prepared at laboratory and production scale (high shear granulation, extrusion/spheronization, drying, and coating). The influence of process parameters on pellet properties (aspect ratio (AR), yield, pellet size, and their distribution) was investigated using static and DIA. During coating, we focused on the coating thickness and identification of potential agglomeration. RESULTS AND CONCLUSION: The effects of kneading time, amount of water, extrusion screen plate (ESP) opening diameter and thickness on pellet properties were confirmed in accordance with literature. In terms of screw speed, spheronization speed and time, no considerable influence on pellet properties was observed in the range of studied process parameters, thereby confirming the design space. In addition to the ESP thickness and opening diameter, quality of the ESP impacts the pellet properties. Lastly, coating thickness measurements with dynamic and static image analysis were comparable and an exemplary case of in-line agglomeration detection was presented. Real-time evaluation with PATVIS APA is an effective PAT tool for the evaluation of spheronization (pellet size distribution, AR, and yield) and coating (coating thickness, agglomeration detection).

Near-infrared hyperspectral imaging of water evaporation dynamics for early detection of incipient caries.

OBJECTIVES: Incipient caries is characterized as demineralization of the tooth enamel reflecting in increased porosity of enamel structure. As a result, the demineralized enamel may contain increased amount of water, and exhibit different water evaporation dynamics than the sound enamel. The objective of this paper is to assess the applicability of water evaporation dynamics of sound and demineralized enamel for detection and quantification of incipient caries using near-infrared hyperspectral imaging. METHODS: The time lapse of water evaporation from enamel samples with artificial and natural caries lesions of different stages was imaged by a near-infrared hyperspectral imaging system. Partial least squares regression was used to predict the water content from the acquired spectra. The water evaporation dynamics was characterized by a first order logarithmic drying model. The calculated time constants of the logarithmic drying model were used as the discriminative feature. RESULTS: The conducted measurements showed that demineralized enamel contains more water and exhibits significantly faster water evaporation than the sound enamel. By appropriate modelling of the water evaporation process from the enamel surface, the contrast between the sound and demineralized enamel observed in the individual near infrared spectral images can be substantially enhanced. CONCLUSIONS: The presented results indicate that near-infrared based prediction of water content combined with an appropriate drying model presents a strong foundation for development of novel diagnostic tools for incipient caries detection. CLINICAL SIGNIFICANCE: The results of the study enhance the understanding of the water evaporation process from the sound and demineralized enamel and have significant implications for the detection of incipient caries by near-infrared hyperspectral imaging.

Automated tracking and analysis of phospholipid vesicle contours in phase contrast microscopy images.

In this article, we propose a method for automated tracking and analysis of vesicle contours in video sequences acquired by phase contrast microscopy. The contour is determined in each frame of the selected video sequence by detecting the transition between the interior and exterior of the vesicle that is reflected in the image intensity gradients. The resulting contour points are represented in the polar coordinate system, i.e., with uniform angular sampling and with coordinates that originate from the vesicle center of mass, enabling the analysis of the vesicle shape and its membrane fluctuations. By analyzing artificial images with known ground-truth contours, the accuracy and precision of the proposed method was estimated to be 34.1 and 26.9 nm for image signal-to-noise ratio of 23 dB and pixel size of 35 nm, respectively. The proposed method was evaluated on quasi-spherical vesicles made up of different proportions of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol and exposed to different temperatures. The results show that the method is robust and efficient in terms of speed and quantitative description of vesicle fluctuations. The magnitude of vesicle membrane fluctuations increased with temperature, while the bending rigidity of the membrane was increasing for temperatures up to 20 °C and decreasing for higher temperatures irrespective of the vesicle molecular structure.