Recent progress in continuous and semi-continuous processing of solid oral dosage forms: a review

Context: Continuous processing is an innovative production concept well known and successfully used in other industries for many years. The modern pharmaceutical industry is facing the challenge of transition from a traditional manufacturing approach based on batch-wise production to a continuous manufacturing model.

Objective: The aim of this article is to present technological progress in manufacturing based on continuous and semi-continuous processing of the solid oral dosage forms.

Methods: Single unit processes possessing an alternative processing pathway to batch-wise technology or, with some modification, an altered approach that may run continuously, and are thus able to seamlessly switch to continuous manufacturing are briefly presented. Furthermore, the concept of semi-continuous processing is discussed. Subsequently, more sophisticated production systems created by coupling single unit processes and comprising all the steps of production, from powder to final dosage form, were reviewed. Finally, attempts of end-to-end production approach, meaning the linking of continuous synthesis of API from intermediates with the production of final dosage form, are described.

Results: There are a growing number of scientific articles showing an increasing interest in changing the approach to the production of pharmaceuticals in recent years. Numerous scientific publications are a source of information on the progress of knowledge and achievements of continuous processing. These works often deal with issues of how to modify or replace the unit processes in order to enable seamlessly switching them into continuous processing. A growing number of research papers concentrate on integrated continuous manufacturing lines in which the production concept of “from powder to tablet” is realized. Four main domains are under investigation: influence of process parameters on intermediates or final dosage forms properties, implementation of process analytical tools, control-managing system responsible for keeping continuous materials flow through the whole manufacturing process and the development of new computational methods to assess or simulate these new manufacturing techniques. The attempt to connect the primary and secondary production steps proves that development of continuously operating lines is possible.

Conclusion: A mind-set change is needed to be able to face, and fully assess, the advantages and disadvantages of switching from batch to continuous mode production.     

Magnetic Ordering of Dy3+ Ions in RbDy(WO4)2 Single Crystal

The specific heat C(T) of the monoclinic RbDy(WO ₄ ) ₂ crystal has been studied at very low temperatures 0.2T1.9 K and in magnetic fields 0H0.38 T. The Neel temperature was shown to be equal to T_N = 0.818 ± 0.005 K. The experimental value of the effective exchange parameter was obtained to be equal to J/k = – 0.798 K. The C T) dependence below Neel temperature 0.5T_N0.99T_N ) is well described by 2D Ising model, whereas in the temperature region close above T_N (1.01 T_N2T_N) it can be described by neither 2D, nor 3D Ising model. The experimental and theoretical H-T_N diagrams for field H a are in a reasonable agreement for simple quadratic lattice.     

On the quantum and randomized approximation of linear functionals on function spaces

We deal with quantum and randomized algorithms for approximating a class of linear continuous functionals. The functionals are defined on a H?lder space of functions f of d variables with r continuous partial derivatives, the rth derivative being a H?lder function with exponent ρ. For a certain class of such linear problems (which includes the integration problem), we define algorithms based on partitioning the domain of f into a large number of small subdomains, and making use of the well-known quantum or randomized algorithms for summation of real numbers. For N information evaluations (quantum queries in the quantum setting), we show upper bounds on the error of order N ^−(γ+1) in the quantum setting, and N ^−(γ+1/2) in the randomized setting, where γ = (r + ρ)/d is the regularity parameter. Hence, we obtain for a wider class of linear problems the same upper bounds as those known for the integration problem. We give examples of functionals satisfying the assumptions, among which we discuss functionals defined on the solution of Fredholm integral equations of the second kind, with complete information about the kernel. We also provide lower bounds, showing in some cases sharpness of the obtained results, and compare the power of quantum, randomized and deterministic algorithms for the exemplary problems.     

Angle-of-arrival localization based on antenna arrays for wireless sensor networks

Among the large number of contributions concerning the localization techniques for wireless sensor networks (WSNs), there is still no simple, energy and cost efficient solution suitable in outdoor scenarios. In this paper, a technique based on antenna arrays and angle-of-arrival (AoA) measurements is carefully discussed. While the AoA algorithms are rarely considered for WSNs due to the large dimensions of directional antennas, some system configurations are investigated that can be easily incorporated in pocket-size wireless devices.A heuristic weighting function that enables decreasing the location errors is introduced. Also, the detailed performance analysis of the presented system is provided. The localization accuracy is validated through realistic Monte-Carlo simulations that take into account the specificity of propagation conditions in WSNs as well as the radio noise effects. Finally, trade-offs between the accuracy, localization time and the number of anchors in a network are addressed.     

Collision-free control of an omni-directional vehicle

This study addresses the problem of controlling an omni-directional vehicle with both state and control dependent constraints. The task of the vehicle is to attain its desired final position given in the task space. The control constraints resulting from the physical abilities of actuators driving the vehicle wheels are also taken into account during the robot movement. The problem of collision avoidance is solved here based on an exterior penalty function approach which results in smooth vehicle velocities near obstacles. Provided that, a solution to the aforementioned vehicle task exists, the Lyapunov stability theory is used to derive the control scheme. The numerical simulation results carried out for the omni-directional vehicle operating in both a constraint-free task space and task space including obstacles, illustrate the performance of the proposed controllers.