Efficient Communication Scheme for Bluetooth Low Energy in Large Scale Applications.

The use of Bluetooth Low Energy (BLE) in the Internet-of-Things (IoT) applications has become widespread and popular. This has resulted in the increased number of deployed BLE devices. To ensure energy efficiency, applications use connectionless communication where nodes broadcast information using advertisement messages. As the BLE devices compete for access to spectrum, collisions are inevitable and methods that improve device coexistence are required. This paper proposes a connectionless communication scheme for BLE that improves communication efficiency in IoT applications where a large number of BLE nodes operate in the same area and communicate simultaneously to a central server. The proposed scheme is based on an active scanning mode and is compared with a typical application where passive scanning mode is used. The evaluation is based on numerical simulations and real-life evaluation of a network containing 150 devices. The presented scheme significantly reduces the number of messages transmitted by each node and decreases packet loss ratio. It also improves the energy efficiency and preserves the battery of BLE nodes as they transmit fewer radio messages and effectively spent less time actively communicating. The proposed connectionless BLE communication scheme can be applied to a large variety of IoT applications improving their performance and coexistence with other devices operating in the 2.4 GHz band. Additionally, the implementation complexity and costs of the proposed communication scheme are negligible.

Physiologically Based Dissolution Testing in a Drug Development Process-a Case Study of a Successful Application in a Bioequivalence Study of Trazodone ER Formulations Under Fed Conditions.

Development of generic extended-release (ER) formulations is challenging. Especially under fed conditions, the risk of failure in bioequivalence trials is high because of long gastric residence times and susceptibility to food effects. We describe the development of a generic trazodone ER formulation that was aided with a biorelevant dissolution evaluation. Trazodone hydrochloride 300-mg monolithic matrix tablets were dissolved both in USP and EMA compliant conditions and in the StressTest device that simulated both physicochemical and mechanical conditions of the gastrointestinal passage. The final formulation was tested against the originator, Trittico XR 300 mg, in a randomized cross-over bioequivalence trial with 44 healthy volunteers, in agreement with EMA guidelines. Initially developed formulations dissolved trazodone similarly to the originator under standard conditions (f2 factor above 50), but their dissolution kinetics differed significantly in the biorelevant tests. The formulation was optimized by the addition of low-viscosity hypromellose and mannitol. The final formulation was approved for the bioequivalence trial. Calculated Cmax were 1.92 ± 0.77 and 1.92 ± 0.63 [µg/mL], AUC0-t were 27.46 ± 8.39 and 29.96 ± 9.09 [µg∙h/mL], and AUC0-∞ were 28.22 ± 8.91 and 30.82 ± 9.41 [µg∙h/mL] for the originator and test formulations, respectively. The 90% confidence intervals of all primary pharmacokinetic parameters fell within the 80-125% range. In summary, biorelevant dissolution tests supported successful development of a generic trazodone ER formulation pharmaceutically equivalent with the originator under fed conditions. Employment of biorelevant dissolution tests may decrease the risk of failure in bioequivalence trials of ER formulations.

A novel open source tool for ELISA result analysis.

ELISA has become a standard analytical tool in the numerous branches of science and industry. Processing of the ELISA results may be a multistep process, often requiring a prior adaptation, using proprietary software, or exporting the results into external internet platforms. It may be problematic in the light of good documentation practices and maintaining good data integrity. In this paper, we present the development and application of the ELISA Tool software. The program is based on a Python scripting programming language and is available under an open-source license. The ELISA Tool allows users to fully control and validate the calculation procedure through a user-friendly graphical user interface. The modular architecture of the software allows its application in other information technology (IT) projects used for data processing in research laboratories. We successfully applied the ELISA Tool for the analysis of real-life samples. The ELISA Tool allowed import of the measurement data, an approximation of the calibration curves with two different algorithms, exploration and diagnostics of the model fit, and generation of the final report with the calculations while maintaining the raw data file unchanged. We report here for the first time the implementation of the idea of full control over data processing, from measured raw data to the final report. We obtained a transparent, open, registered system of data processing control, independent of third parties. The modular and flexible architecture of the created software encourages its further development following the individual demands of the users.

Biorelevant In Vitro Release Testing and In Vivo Study of Extended-Release Niacin Hydrophilic Matrix Tablets.

Niacin (nicotinic acid, NA) is administered orally as an antihyperlipidemic agent in extended-release (ER) tablets in high doses. Due to rapid absorption and extensive metabolism (non-linear pharmacokinetics), the drug plasma levels are highly variable, which may correlate with side effects. Interestingly, this erratic drug delivery behavior of niacin ER products cannot be clarified by compendial in vitro release testing. The standard dissolution tests do not allow to mimic the selected GI tract characteristics in order to estimate the robustness of formulation under the variability of the physiological conditions. These are characterized by the pH value, impact of motility forces and composition, as well as volume of GI liquids. Our paper demonstrates a comparison of a newly developed ER HPMC niacin formulation with an originator product. The research aimed to design a robust matrix tablet of comparable biopharmaceutical behavior, safety and efficacy. The extensive in vitro investigation, including dynamic studies in flow-through cell apparatus and stress test device, forms the basis for the evaluation of nicotinic acid plasma concentrations in vivo. The occurrence of erratic, multiple NA plasma peaks after the administration of both extended-release products is a result of its local input excess over the metabolic threshold (at the level corresponding to maximum 2% of the administered dose, i.e., 20 mg of drug) due to the mechanical stresses of physiological intensity. We demonstrate how this behavior is similar for both marketed and test products. In this context, we describe how a robust ER matrix and well-designed formulation does not guarantee the test product's bioequivalence to the comparator one out of reasons unrelated to technology and biopharmaceutical properties, but because of the active compound's intrinsic pharmacokinetic characteristics, i.e., highly variable, extensive metabolism of nicotinic acid.

Experimental Evaluation of Advertisement-Based Bluetooth Low Energy Communication.

This paper addresses the efficiency of Bluetooth Low Energy (BLE) communication in a network composed of a large number of tags that transmit information to a single hub using advertisement mode. Theoretical results show that the use of advertisements enables hundreds and thousands of BLE devices to coexist in the same area and at the same time effectively transmit messages. Together with other properties (low power consumption, medium communication range, capability to detect a signal's angle-of-arrival, etc.), this makes BLE a competing technology for the Internet of Things (IoT) applications. However, as the number of communicating devices increases, the advertisement collision intensifies and the communication performance of BLE drops. This phenomena was so far analyzed theoretically, in simulations and in small-scale experiments, but large-scale experiments are not presented in the literature. This paper complements previous results and presents an experimental evaluation of a real IoT-use case, which is the deployment of over 200 tags communicating using advertisements. We evaluate the impact of the number of advertisements on the effective data reception rate and throughput. Despite the advertisement collision rate in our experiment varying between 0.22 and 0.33, we show that BLE, thanks to the multiple transmission of advertisements, can still ensure acceptable data reception rates and fulfill the requirements of a wide range of IoT applications.