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. 相似文献
In this work we present studies on applicability of transition metal additives as sintering and electrical conductivity aids for cerium gadolinium oxide electrolyte. The nanosized Ce0.85Gd0.15O1.925 powder obtained by coprecipitation method was modified with Cr3+, Fe3+, Ni2+ or Cu2+ ions. Using high-intensity high-resolution X-ray powder diffraction data we have determined that Cr, Fe and Ni ions do not incorporate into the cerium gadolinium oxide surface or bulk when sintered at 1300 °C, but react with Gd ions to form Cr0.9Gd0.1O, GdFeO3 and GdNiO3 phases, while Cu incorporates in the material up to 0.7 mol% with a significant fraction of remaining material showing poorly crystalline CuO phase. The nanosized Ce0.85Gd0.15O1.925 material shows already improved sintering properties than previous reports but full sintering is not achieved below 1300 °C, however Cr, Fe and mainly Cu impregnation allows full sintering at 1300 °C. 0.5 mol% Ni impregnated material sintered at 1500 °C shows enhanced grain boundary conductivity that probably indicates that Ni incorporates into Ce0.84Gd0.15O1.925 above 1300 °C. The global results indicate, however, that optimization of ceria microstructure is at least of equal importance for sinterability and grain boundary conductivity than impregnation of the material with transition metal ions. 相似文献
We have modeled surface impedance of YBa2Cu3O7– thin films, using an exponential dependence on an applied rf magnetic field. For verification of the model we compared simulation results with experimental data of Nguyen et al. [2] and of Hein [14] at differing temperatures, frequencies and rf power levels. Obtained temperature dependence of the model fitting coefficients exhibited the same character in both cases. 相似文献
Waste motor and transformer oils are considered as a main source of polychlorinated biphenyls (PCBs) emission into the environment. The levels of total PCB in twenty six randomly selected samples of waste motor and transformer oils from different regions of Poland were studied. The clean-up of the extracts on two solid phase extraction columns system and determination of PCBs by capillary gas chromatography with electron capture detection were performed. The determined content of PCBs in motor oils was by one order of magnitude higher than in transformer oils, but in the both types of analysed samples, except one sample, did not exceed 50 micrograms/g. 相似文献
By adding a gold core to silica nanoparticles (BrightSilica), silica‐like nanoparticles are generated that, unlike unmodified silica nanoparticles, provide three types of complementary information to investigate the silica nano‐biointeraction inside eukaryotic cells in situ. Firstly, organic molecules in proximity of and penetrating into the silica shell in live cells are monitored by surface‐enhanced Raman scattering (SERS). The SERS data show interaction of the hybrid silica particles with tyrosine, cysteine and phenylalanine side chains of adsorbed proteins. Composition of the biomolecular corona of BrightSilica nanoparticles differs in fibroblast and macrophage cells. Secondly, quantification of the BrightSilica nanoparticles using laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) micromapping indicates a different interaction of silica nanoparticles compared to gold nanoparticles under the same experimental conditions. Thirdly, the metal cores allow the investigation of particle distribution and interaction in the cellular ultrastructure by cryo nanoscale X‐ray tomography (cryo‐XT). In 3D reconstructions the assumption is confirmed that BrightSilica nanoparticles enter cells by an endocytotic mechanism. The high SERS intensities are explained by the beneficial plasmonic properties due to agglomeration of BrightSilica. The results have implications for the development of multi‐modal qualitative and quantitative characterization in comparative nanotoxicology and bionanotechnology. 相似文献
This article discusses thermal analysis of different molecular weight poly(2-ethylhexyl acrylates) synthesized by radical polymerization of 2-ethylhexyl acrylate. The main aim of this work was to investigate the thermal properties and degradation process of synthesized acrylic homopolymers and forming of thermal degradation products during their pyrolysis. As investigated method pyrolysis combined with gas chromatography was used. Poly(2-ethylhexyl acrylates) are used as plasticizers for pressure-sensitive adhesives applied in medical area. 相似文献
Bamberger ring cleavage acylation of N-p-toluenesulfonyl (tosyl) histamine followed by hydrogenation yields 3,4-diacylaminobutanetosylamine, a triamine containing groups with different chemical reactivities. 相似文献
Colloidal 5.1 wt% Ru/γ-Al2O3 catalyst was prepared by a microwave assisted, solvothermal reduction of RuCl3 in ethylene glycol in the presence of γ-Al2O3. The catalyst subjected to heat-treatment in hydrogen up to 700 °C, was characterized by BET, XRD, TEM and H2 chemisorption. As-prepared catalyst contained Ru nanoparticles with mean size of 1.5 nm and narrow size distribution uniformly distributed over the support. The nanoparticles were stable on the alumina to 500 °C, but treatment at 600–700 °C caused some sintering of Ru due to migration and coalescence of a part of smallest ruthenium nanoparticles. However, even after H2 treatment at 700 °C, large amount of Ru nanoparticles with sizes of 1–3 nm remained in the catalyst. H2 chemisorption data revealed decrease of Ru dispersion from 0.28 to 0.19 by hydrogen treatment at 700 °C and were in good correspondence with TEM results. On the contrary, mean crystallite sizes obtained from XRD were strongly overestimated. 相似文献