Continuous direct compression as manufacturing platform for sustained release tablets

This study presents a framework for process and product development on a continuous direct compression manufacturing platform. A challenging sustained release formulation with high content of a poorly flowing low density drug was selected. Two HPMC grades were evaluated as matrix former: standard Methocel CR and directly compressible Methocel DC2. The feeding behavior of each formulation component was investigated by deriving feed factor profiles. The maximum feed factor was used to estimate the drive command and depended strongly upon the density of the material. Furthermore, the shape of the feed factor profile allowed definition of a customized refill regime for each material. Inline NIRs was used to estimate the residence time distribution (RTD) in the mixer and monitor blend uniformity. Tablet content and weight variability were determined as additional measures of mixing performance. For Methocel CR, the best axial mixing (i.e. feeder fluctuation dampening) was achieved when an impeller with high number of radial mixing blades operated at low speed. However, the variability in tablet weight and content uniformity deteriorated under this condition. One can therefore conclude that balancing axial mixing with tablet quality is critical for Methocel CR. However, reformulating with the direct compressible Methocel DC2 as matrix former improved tablet quality vastly. Furthermore, both process and product were significantly more robust to changes in process and design variables. This observation underpins the importance of flowability during continuous blending and die-filling. At the compaction stage, blends with Methocel CR showed better tabletability driven by a higher compressibility as the smaller CR particles have a higher bonding area. However, tablets of similar strength were achieved using Methocel DC2 by targeting equal porosity. Compaction pressure impacted tablet properties and dissolution. Hence controlling thickness during continuous manufacturing of sustained release tablets was crucial to ensure reproducible dissolution. (C) 2017 Elsevier B.V. All rights reserved

Twin-screw granulation – a systematic analysis of process parameters

Twin-screw granulation has a significant advantage over traditional granulation methods leading to the possibility of continuous manufacturing. Although this technology has drawn attention in recent years, the general understanding of the process is limited. This study gives a brief overview of the most important process parameters and their influence on product quality. Experimental results from a benchtop granulator and an in-line particle size measurement have been analysed. From this basic study conclusions can be drawn how to tailor the particle size distribution in twin-screw granulation. The most crucial parameters are the liquid-to-solid ratio and the filling level of the screws

Sustainable Materials and Biorefinery Chemicals from Agriwastes

This is an open access chapter distributed under the terms of the Creative Commons Attribution License.-- et al.Countries with economies based on agriculture generate vast amounts of low or null value wastes which may even represent an environmental hazard. In our group, agricultural industrial wastes have been converted into value added liquid substances and materials with several aims: decreasing pollution, giving added value to wastes and working in a sustainable manner in which the wastes of an industry can be used as the raw materials of the same or others, as the “cradle to cradle” philosophy states [1]. Sub-products from the agricultural food industry are being employed as renewable low cost raw materials in the preparation of Ecomaterials, designed for use in a number of industrial processes of great interest. Given their origin, these materials may compete with conventional ones since with this process a sustainable cycle is closed, in which the residues of one industry are used as raw materials in the same or other industries [2]. With regards to the composition of the residues produced from agriculture, the pH of soil is of great importance, since plants can only absorb the minerals that are dissolved in water and pH is mandatory for the physical, chemical and biological properties of soil and the main cause of many agronomic questions related to nutrient assimilation [3-5]. Variations of pH modify the solubility of most elements necessary for the development of crops and also influence the microbian activity of soil, which will affect the transformation of elements that are liberated to the soil and can be assimilated to form crops or not [3]. For example at pH lower than 6 or higher than 8 bacterian activities are lowered, the oxidation of nitrogen to nitrate is reduced and the amount of nitrogen available for plant food is decreased. However Al, Fe and manganese are more soluble at low pHs, reaching even toxic concentrations. Potassium and sulphur are easily adsorbed at pH higher than 6, calcium and magnesium between 7 and 8.5 and iron at pH lower than 6. For alkaline pH in soil, the availability of H2PO4-can be reduced through precipitation of phosphorous containing salts withcations such as calcium Ca2+ or magnesium Mg2+. However when soils have acid pH other compounds with HPO42-and iron (Fe2+), aluminium (Al3+) and manganese (Mn2+) can form, with increased solubility. The main factors that influence soil pH are the mineral composition and how it meteorizes, the decomposition of organic matter, how nutrients are partitioned among the solution and aggregates and of course the pluviometryof the zone and atmospheric contamination.Lower pHs are found in places with high pluviometry, with high organic matter decomposition, young soils developed on acid substrates, and places with high atmospheric contamination (acid rain). Depending on the species, crops can benefit from calcareous soils with high calcium carbonate content such as alfalfa, but other plants prefer soils with acid pH such as potatoes, coffee or tobacco. It is clear that different seasons will produce plants with a varying composition depending on the atmospheric conditions and therefore the materials derived from them need to be characterised and analysed to determine their possible uses.Given its multidisciplinary approach, this work is being carried out through the collaboration among national (Institute of Materials Science of Madrid (ICMM, CSIC), Institute of Catalysis (ICP, CSIC), Centre of Molecular Biology Severo Ochoa (UAM-CSIC), Polytechnic University of Madrid (UPM), University at distance (UNED), University Complutense of Madrid (UPM) and international (University of Sheffield and University of Ghent) research groups, in addition to various industries interested in the transformation of their residues and or sub-products into “value added materials”, with whom various research projects have been and are being sponsored by the MICINN and CDTI.Peer Reviewe