Co-melt fluidised bed granulation of pharmaceutical powders: Improvements in drug bioavailability

This study investigates the use of co-melt fluidised bed granulation for the agglomeration of model pharmaceutical powders, namely, lactose mono-hydrate, PEG 10000, poly-vinyl pyrolidone and ibuprofen as a model drug. Granulation within the co-melt system was found to follow a nucleationâ??steady growthâ??coating regime profile. Using high molecular weight PEG binder, the granulation mechanism and thus the extent of granulation was found to be significantly influenced by binder viscosity. The compression properties of the granulate within the hot fluidised bed were correlated using a novel high temperature experimental procedure. It was found that the fracture stress and fractural modulus of the materials under hot processing conditions were orders of magnitude lower than those measured under ambient conditions. A range of particle velocities within the granulator were considered based on theoretical models. After an initial period of nucleation, the Stokes deformation number analysis indicated that only velocities within the high shear region of the fluidised bed were sufficient to promote significant granule deformation and therefore, coalescence. The data also indicated that larger granules de-fluidised preventing agglomeration by coalescence. Furthermore, experimental data indicated that dissipation of the viscous molten binder to the surface was the most important factor in the latter stages of the granulation process. From a pharmaceutical perspective the inclusion of the model drug, ibuprofen, combined with PVP in the co-melt process proved to be highly significant. It was found that using DSC analysis on the formulations that the decrease in the heat of fusion associated with the melting of ibuprofen within the FHMG systems may be attributed to interaction between PVP and ibuprofen through inter-molecular hydrogen bonding. This interaction decreases the crystallinity of ibuprofen and facilitates solubilisation and bioavailability within the solid matrix.

Improved Equivalent Frame Analysis Method for Flat Plate Structures in Vicinity of Edge Columns

This paper proposes a modification to the ACI 318-02 equivalent frame method of analysis of reinforced concrete flat plate exterior panels. Two existing code methods were examined: ACI 318 and BS 8110. The derivation of the torsional stiffness of the edge strip as proposed by ACI 318 is examined and a more accurate estimate of this value is proposed, based on both theoretical analysis and experimental results. A series of 1/3-scale models of flat plate exterior panels have been tested. Unique experimental results were obtained by measuring strains in reinforcing bars at approximately 200 selected locations in the plate panel throughout the entire loading history. The measured strains were used to calculate curvature and, hence, bending moments; these were used along with moments in the columns to assess the accuracy of the equivalent frame methods. The proposed method leads to a more accurate prediction of the moments in the plate at the column front face, at the panel midspan, and in the edge column. Registered Subscribers: View the full article. This document is available as a free download to qualified members. An electronic (PDF) version is available for purchase and download. Click on the Order Now button to continue with the download.

Anti-sized reed bed system for animal wastewater treatment: a comparative study

This paper presents a comparative study on the treatment of high-strength animal wastewater in two parallel lab-scale constructed reed bed systems, progressively-sized system and anti-sized system, which have same configuration but different arrangement of bed media. The reed bed systems were operated in a tidal flow pattern to treat diluted pig slurry. Detailed analyses were carried out for the removal of some key pollutants including COD, BOD5, NH4-N, P and suspended solids. The results showed that both systems have considerable capacity for the removal of solids, organic matter and inorganic nutrients. The formation of biofilms on the surfaces of gravel media in both reed bed systems was monitored by scanning selected gravel samples using scanning electron microscopy. In general, no significant difference was detected with regard to the percentage pollutant removal in the systems. However, the anti-sized system demonstrated a clear advantage in its ability to slow down the clogging of bed media and avoid the impairment of long-term functioning and sustainability of the beds. A conceptual model was developed to predict the occurrence of the clogging. The validity of the model was tested using data from this study and from the literatures.

Purification capacity of a highly loaded laboratory scale tidal flow reed bed system with effluent recirculation

The purification capacity of a laboratory scale tidal flow reed bed system with final effluent recirculation at a ratio of 1:1 was investigated in this study. In particular, this four-stage reed bed system was highly loaded with strong agricultural wastewater. Under the hydraulic and organic loading rates as high as 0.43 m3/m2d and 1055 gCOD/m2d, respectively, the average removal efficiencies of COD, BOD5, SS, NH4-N and P were 77%, 78%, 66%, 62% and 38%. Even with the high loading rates, approximately 30% of NH4-N was converted into NO2-N and NO3-N from the mid-stage of the system where nitrification took place. The results suggest that the multi-stage reed bed system could be employed to treat strong wastewater under high loading, especially for the substantive mass removal of solids, organic matter and ammoniacal-nitrogen. Tidal flow combined with effluent recirculation is a favourable operation strategy to achieve this objective.

Influence of prolonged hospitalization on overall bed occupancy: a five-year single-centre study

Background: Effective bed use is crucial to an efficient NHS. Current targets suggest a decrease in mean occupancy as the most appropriate method of improving overall efficiency. The elderly and those suffering from complex medical problems are thought to account for a high proportion of overall bed occupancy.

Aim: To assess the effect of prolonged hospital stay (>100 days) on overall bed occupancy in a modern teaching hospital.

Design: Retrospective analysis.

Methods: Analysis of all admission episodes (n = 117 178) over a five-year period in a large teaching hospital in a single UK region, serving a population of approximately 200 000. A logistic regression multi-factorial model was used to assess the effect of demographic and diagnostic variables on duration of stay.

Results: A prolonged stay (>100 days) was seen in 648 admission episodes (0.6%). These accounted for 11% of the overall bed occupancy over the 5-year period. Excluding all prolonged admission episodes from our analysis made no difference to the overall median length of stay.

Discussion: Prolonged hospitalizations have a significant impact on bed occupancy. Targeting these very long (>100 days) hospital stays may better improve overall efficiency, compared to targeting mean or median length of stay.

A quantitative determination of reaction mechanisms from density functional theory calculations: Fischer-Tropsch synthesis on flat and stepped cobalt surfaces

We systematically investigated the mechanism of the C-1 + C-1 coupling reactions using density functional theory. The activation energies of C-1 + C-1 coupling and carbon hydrogenation reactions on both flat and stepped surfaces were calculated and analyzed. Moreover, the coverages of adsorbed C-1 species were estimated, and the reaction rates of all possible C-1 + C-1 coupling pathways were quantitatively evaluated. The results suggest that the reactions of CH2 + CH2 and CH3 + C at steps are most likely to be the key C-1 + C-1 coupling steps in FT synthesis on Co catalysts. The reactions of C-2 + C-1 and C-3 + C-1 coupling also were studied; the results demonstrate that in addition to the pathways of RCH + CH2 and RCH2 + C, the coupling of RC + C and RC + CH also may contribute to the chain growth after C-1. (C) 2008 Elsevier Inc. All rights reserved.

Characterisation of fluidised bed granulation processes using in situ Raman spectroscopy

Previous work by the authors Walker et al. [2007b. Fluidised bed characterisation using Raman spectroscopy: applications to pharmaceutical processing. Chemical Engineering Science 62, 3832–3838] illustrated that Raman spectroscopy could be used to provide 3-D maps of the concentration and chemical structure of particles in motion in a fluidised bed, within a relatively short (120 s) time window. Moreover, we reported that the technique, as outlined, has the potential to give detailed in-situ information on how the structure and composition of granules/powders within the fluidised bed (dryer or granulator) vary with the position and evolve with time. In this study we extended the original work by shortening the time window of the Raman spectroscopic analysis to 10 s, which has allowed the in-situ real-time characterisation of a fluidised bed granulation process. Here we show an important new use of the technique which allows in-situ measurement of the composition of the material within the fluidised bed in three spatial dimensions and as a function of time. This is achieved by recording Raman spectra using a probe positioned within the fluidised bed on a long-travel x–y–z stage. In these experiments the absolute Raman intensity is used to provide a direct measure of the amount of any given material in the probed volume, i.e. a particle density. Particle density profiles have been calculated over the granulation time and show how the volume of the fluidised bed decreases with an increase mean granule size. The Raman spectroscopy analysis indicated that nucleation/coalescence in this co-melt fluidised hot melt granulation system occurred over a relatively short time frame (t<30 s). The Raman spectroscopic technique demonstrated accurate correlation with independent granulation experiments which provided particle size distribution analysis. The similarity of the data indicates that the Raman spectra accurately represent solids ratios within the bed, and thus the techniques quantitative capabilities for future use in the pharmaceutical industry.