Emerging technologies for the non-invasive characterization of physical-mechanical properties of tablets

The density, porosity, breaking force, viscoelastic properties, and the presence or absence of any structural defects or irregularities are important physical-mechanical quality attributes of popular solid dosage forms like tablets. The irregularities associated with these attributes may influence the drug product functionality. Thus, an accurate and efficient characterization of these properties is critical for successful development and manufacturing of a robust tablets. These properties are mainly analyzed and monitored with traditional pharmacopeial and non-pharmacopeial methods. Such methods are associated with several challenges such as lack of spatial resolution, efficiency, or sample-sparing attributes. Recent advances in technology, design, instrumentation, and software have led to the emergence of newer techniques for non-invasive characterization of physical-mechanical properties of tablets. These techniques include near infrared spectroscopy, Raman spectroscopy, X-ray microtomography, nuclear magnetic resonance (NMR) imaging, terahertz pulsed imaging, laser-induced breakdown spectroscopy, and various acoustic- and thermal-based techniques. Such state-of-the-art techniques are currently applied at various stages of development and manufacturing of tablets at industrial scale. Each technique has specific advantages or challenges with respect to operational efficiency and cost, compared to traditional analytical methods. Currently, most of these techniques are used as secondary analytical tools to support the traditional methods in characterizing or monitoring tablet quality attributes. Therefore, further development in the instrumentation and software, and studies on the applications are necessary for their adoption in routine analysis and monitoring of tablet physical-mechanical properties

Near infrared and Raman spectroscopy for the in-process monitoring of pharmaceutical production processes

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Assessment of hemodynamic conditions in the aorta following root replacement with composite valve-conduit graft

This paper presents the analysis of detailed hemodynamics in the aortas of four patients following replacement with a composite bio-prosthetic valve-conduit. Magnetic resonance image-based computational models were set up for each patient with boundary conditions comprising subject-specific three-dimensional inflow velocity profiles at the aortic root and central pressure waveform at the model outlet. Two normal subjects were also included for comparison. The purpose of the study was to investigate the effects of the valve-conduit on flow in the proximal and distal aorta. The results suggested that following the composite valve-conduit implantation, the vortical flow structure and hemodynamic parameters in the aorta were altered, with slightly reduced helical flow index, elevated wall shear stress and higher non-uniformity in wall shear compared to normal aortas. Inter-individual analysis revealed different hemodynamic conditions among the patients depending on the conduit configuration in the ascending aorta, which is a key factor in determining post-operative aortic flow. Introducing a natural curvature in the conduit to create a smooth transition between the conduit and native aorta may help prevent the occurrence of retrograde and recirculating flow in the aortic arch, which is particularly important when a large portion or the entire ascending aorta needs to be replaced

A method for three-dimensional particle sizing in two-phase flows

A method is devised for true three-dimensional (3D) particle sizing in two-phase systems. Based on a ray-optics approximation of the Mie scattering theory for spherical particles, and under given assumptions, the principle is applicable to intensity data from scatterers within arbitrary interrogation volumes. It requires knowledge of the particle 3D location and intensity, and of the spatial distribution of the incident light intensity throughout the measurement volume. The new methodology is particularly suited for Lagrangian measurements: we demonstrate its use with the defocusing digital particle image velocimetry technique, a 3D measurement technique that provides the location, intensity and velocity of particles in large volume domains. We provide a method to characterize the volumetric distribution of the incident illumination and we assess experimentally the size measurement uncertainty

Quality of medicines commonly used in the treatment of soil transmitted helminths and Giardia in Ethiopia: a nationwide survey

Background: The presence of poor quality medicines in the market is a global threat on public health, especially in developing countries. Therefore, we assessed the quality of two commonly used anthelminthic drugs [mebendazole (MEB) and albendazole (ALB)] and one antiprotozoal drug [tinidazole (TNZ)] in Ethiopia. Methods/Principal Findings: A multilevel stratified random sampling, with as strata the different levels of supply chain system in Ethiopia, geographic areas and government/privately owned medicines outlets, was used to collect the drug samples using mystery shoppers. The three drugs (106 samples) were collected from 38 drug outlets (government/privately owned) in 7 major cities in Ethiopia between January and March 2012. All samples underwent visual and physical inspection for labeling and packaging before physico-chemical quality testing and evaluated based on individual monographs in Pharmacopoeias for identification, assay/content, dosage uniformity, dissolution, disintegration and friability. In addition, quality risk was analyzed using failure mode effect analysis (FMEA) and a risk priority number (RPN) was assigned to each quality attribute. A clinically rationalized desirability function was applied in quantification of the overall quality of each medicine. Overall, 45.3% (48/106) of the tested samples were substandard, i.e. not meeting the pharmacopoeial quality specifications claimed by their manufacturers. Assay was the quality attribute most often out-of-specification, with 29.2% (31/106) failure of the total samples. The highest failure was observed for MEB (19/42, 45.2%), followed by TNZ (10/39, 25.6%) and ALB (2/25, 8.0%). The risk analysis showed that assay (RPN = 512) is the most critical quality attribute, followed by dissolution (RPN = 336). Based on Derringer's desirability function, samples were classified into excellent (14/106,13%), good (24/106, 23%), acceptable (38/106, 36%%), low (29/106, 27%) and bad (1/106,1%) quality. Conclusions/Significance: This study evidenced that there is a relatively high prevalence of poor quality MEB, ALB and TNZ in Ethiopia: up to 45% if pharmacopoeial acceptance criteria are used in the traditional, dichotomous approach, and 28% if the new risk-based desirability approach was applied. The study identified assay as the most critical quality attributes. The country of origin was the most significant factor determining poor quality status of the investigated medicines in Ethiopia

Biophotonic Tools in Cell and Tissue Diagnostics.

In order to maintain the rapid advance of biophotonics in the U.S. and enhance our competitiveness worldwide, key measurement tools must be in place. As part of a wide-reaching effort to improve the U.S. technology base, the National Institute of Standards and Technology sponsored a workshop titled "Biophotonic tools for cell and tissue diagnostics." The workshop focused on diagnostic techniques involving the interaction between biological systems and photons. Through invited presentations by industry representatives and panel discussion, near- and far-term measurement needs were evaluated. As a result of this workshop, this document has been prepared on the measurement tools needed for biophotonic cell and tissue diagnostics. This will become a part of the larger measurement road-mapping effort to be presented to the Nation as an assessment of the U.S. Measurement System. The information will be used to highlight measurement needs to the community and to facilitate solutions