Practical high-dimensional quantum key distribution protocol over deployed multicore fiber.

Quantum key distribution (QKD) is a secure communication scheme for sharing symmetric cryptographic keys based on the laws of quantum physics, and is considered a key player in the realm of cyber-security. A critical challenge for QKD systems comes from the fact that the ever-increasing rates at which digital data are transmitted require more and more performing sources of quantum keys, primarily in terms of secret key generation rate. High-dimensional QKD based on path encoding has been proposed as a candidate approach to address this challenge. However, while proof-of-principle demonstrations based on lab experiments have been reported in the literature, demonstrations in realistic environments are still missing. Here we report the generation of secret keys in a 4-dimensional hybrid time-path-encoded QKD system over a 52-km deployed multicore fiber link forming by looping back two cores of a 26-km 4-core optical fiber. Our results indicate that robust high-dimensional QKD can be implemented in a realistic environment by combining standard telecom equipment with emerging multicore fiber technology.

Tryptophan Analogues with Fixed Side-Chain Orientation: Expanding the Scope.

A generalized synthetic strategy is proposed here for the synthesis of asymmetric ß-indoylated amino acids by 8-aminoquinoline (8AQ)-directed C(sp3)-H functionalization of suitably protected precursors. Peptides containing one of the four stereoisomers of (indol-3-yl)-3-phenylalanine at position 2 of the parent peptide KwFwLL-NH2 (w=d-Trp) cover a wide range of activities as ghrelin receptor inverse agonists, among them the most active described until now. This application exemplarily shows how ß-indoylated amino acids can be used for the systematic variation of the position of an indole group in a bioactive peptide.

Side Chain Orientation of Tryptophan Analogues Determines Agonism and Inverse Agonism in Short Ghrelin Peptides.

We describe two synthetic amino acids with inverted side chain stereochemistry, which induce opposite biological activity. Phe4 is an important part of the activation motif of ghrelin, and in short peptide inverse agonists such as KwFwLL-NH2 , the aromatic core is necessary for inactivation of the receptor. To restrict indole/phenyl mobility and simultaneously strengthen the interaction between peptide and receptor, we exchanged the natural monoaryl amino acids for diaryl amino acids derived from tryptophan. By standard solid-phase peptide synthesis, each of them was inserted into ghrelin or in the aromatic core of the inverse agonist. Both ghrelin analogues showed nanomolar activity, indicating sufficient space to accommodate the additional side chain. In contrast, diaryl amino acids in the inverse agonist had considerable influence on receptor signaling. Whereas the introduction of Wsf maintains inverse agonism of the peptide, Wrf shifts the receptor more to active states and can induce agonism depending on its introduction site.

Investigating dissolution performance critical areas on coated tablets: a case study using terahertz pulsed imaging.

During the process development of coated tablets, knowledge on the formation and the location of film coating 'weak spots' is a key factor to the success of the process and the resulting product batch. It is understood that the performance of the product batch may be greatly limited, and often compromised, by weak spots on the tablet film coat. This study uses circular, biconvex tablets to investigate the ability of terahertz pulsed imaging (TPI) to identify the affected areas on the tablet film coat that are critical for dissolution performance. From the TPI analysis we determined that the tablet central band exhibited the thinnest film coating, lowest coating density and highest surface roughness and thus was the performance limiting area of the film coating. Dissolution tests confirmed that the film coating on the tablet central band was indeed dissolution rate determining, with a faster mean dissolution time (MDT) of 7.4 h in comparison to 10.4 h for the convex top/bottom surface. TPI, as a nondestructive analytical technique, showed potential to be employed as a process analytical tool to probe film coating weak spots during film coating development and to assess the effect on the subsequent dissolution performance.

Monitoring the film coating unit operation and predicting drug dissolution using terahertz pulsed imaging.

Understanding the coating unit operation is imperative to improve product quality and reduce output risks for coated solid dosage forms. Three batches of sustained-release tablets coated with the same process parameters (pan speed, spray rate, etc.) were subjected to terahertz pulsed imaging (TPI) analysis followed by dissolution testing. Mean dissolution times (MDT) from conventional dissolution testing were correlated with terahertz waveforms, which yielded a multivariate, partial least squares regression (PLS) model with an R(2) of 0.92 for the calibration set and 0.91 for the validation set. This two-component, PLS model was built from batch I that was coated in the same environmental conditions (air temperature, humidity, etc.) to that of batch II but at different environmental conditions from batch III. The MDTs of batch II was predicted in a nondestructive manner with the developed PLS model and the accuracy of the predicted values were subsequently validated with conventional dissolution testing and found to be in good agreement. The terahertz PLS model was also shown to be sensitive to changes in the coating conditions, successfully identifying the larger coating variability in batch III. In this study, we demonstrated that TPI in conjunction with PLS analysis could be employed to assist with film coating process understanding and provide predictions on drug dissolution.

Terahertz pulsed imaging as an analytical tool for sustained-release tablet film coating.

The ability of terahertz pulsed imaging (TPI) to be employed as an analytical tool for monitoring a film coating unit operation and to assess the success of a subsequent process scale-up was explored in this study. As part of a process scale-up development, a total of 190 sustained-release tablets were sampled at 10% increments of the amount of polymer applied, from a lab-scale and a pilot-scale coating run. These tablets were subjected to TPI analysis, followed by dissolution testing. Information on tablet film coating layer thickness and variations in coating density were extracted using TPI. It was found that both terahertz parameters were more sensitive and informative to product quality when compared with measuring the amount of polymer applied. For monitoring the film coating unit operation, coating layer thickness showed a strong influence on the dissolution behaviour for both the lab-scale and the pilot-scale batches. An R(2) of 0.89, root mean square error (RMSE)=0.22 h (MDT range=3.21-5.48 h) and an R(2) of 0.92, RMSE=0.23 h (MDT range=5.43-8.12 h) were derived from the lab-scale and pilot-scale, respectively. The scale-up process led to significant changes in MDT between the lab-scale and pilot-scale. These changes in MDT could be explained by the differences observed in the film coating density on samples with similar amount of polymer applied between the lab and the pilot-scale. Overall, TPI demonstrated potential to be employed as an analytical tool to help refine the coating unit operation and the scale-up procedure.

Applications of terahertz pulsed imaging to sustained-release tablet film coating quality assessment and dissolution performance.

The potential of terahertz pulsed imaging (TPI) to predict the dissolution performance in sustained-release tablets was investigated in this study. Batches of coated tablets with similar weight gain during the coating process at the lab and pilot scales were subjected to non-destructive imaging by TPI and subsequently analysed by dissolution testing. The results from the dissolution tests revealed significant differences in the product performance between the lab and pilot scales (Student t-test, P<0.05). The model-independent dissolution parameters in the pilot scale showed a prolonged mean dissolution time. This indicated that the pharmaceutical active ingredient was released at a slower rate in the pilot compared to the lab scale. While weight gain measurements (the traditional coating quality parameter), failed to provide an early indication of the product functional performance; terahertz parameters (terahertz electric field peak strength and coating layer thickness) provided insight into the subsequent dissolution behaviour. Correlations between terahertz parameters and dissolution were much stronger than correlations between weight gain and dissolution; with the R(2) value for terahertz correlations typically around 0.84 as opposed to 0.07 for weight gain correlations. This study presents the initial finding of correlations between terahertz parameters for assessing the coating quality to the dissolution performance of the coated tablet. The contributing factors for these particular correlations are also discussed.

Comparison study of laboratory and production spray guns in film coating: effect of pattern air and nozzle diameter.

An optimal atomization air/pattern air ratio is necessary for a good coating process. The influences of variations in pattern air and nozzle diameter on the spray characteristics, such as droplet size, droplet velocity, and spray density, are investigated by using laboratory and production Schlick spray guns, both equipped with a new antibearding cap (ABC). An increase in the pattern air results in a wider spray accompanied with a decrease in droplet size in the spray center for both spray guns. Furthermore, an increase in the pattern air leads to a reduction in spray density in the spray center and, simultaneously, to an increase in spray density at the spray rim. A variation in nozzle diameter does not influence the spray characteristics for both spray guns.