Modelling dosator filling and discharge of powder

Dosators and other dosing mechanisms operating on generally similar principles are very widely used in the pharmaceutical industry for capsule filling, and for dosing products that are delivered to the customer in powder form such as inhalers. This is a trend that is set to increase. However a significant problem for this technology is being able to predict how accurately and reliably, new drug formulations will be dosed from these machines prior to manufacture. This paper presents a review of the literature relating to powder dosators which considers mathematical models for predicting dosator performance, the effects of the dosator geometry and machine settings on the accuracy of the dose weight. An overview of a model based on classical powder mechanics theory that has been developed at The University of Greenwich is presented. The model uses inputs from a range of powder characterisation tests including, wall friction, bulk density, stress ratio and permeability. To validate the model it is anticipated that it will be trialled for a range of powders alongside a single shot dosator test rig.

Direct measurement of powder flavour adhesion on to a food surface using a novel adhesion tester

The firm adhesion of flavouring particles onto crisp surfaces during coating processes is a major concern in the snack production industry. Detachment of flavouring powders from products during handling and production stages can lead to substantial financial losses for the industry, in terms of variable flavour performance and extended cleaning down time of fugitive particle build-up on process equipment. Understanding the adhesion strength of applied bulk particulates used for flavouring formulations will help analysts to evaluate the efficiency of coating processes and potentially enable them to assess the adhesion strength of newly formulated flavouring powder prior to commitment to full scale plant trials. A rapid prototype of a novel adhesion tester has been designed and constructed. The apparatus operates according to the principle of impact force acting on particles attached to the surface of the food substrate. The main component is a circular plate to which four sample holders are attached and which is subjected to vertical travel down a guide shaft. Several flavouring powders have been tested extensively. By plotting the detachment versus impact force, the difference obtained between adhesion strength of different flavouring powders (which is a strong function of particle size) has been discussed.

Modelling metal powder production by the gas atomisation process

Metal powder in the range of 10-100 microns is widely employed in the production of Raney nickel type catalysts for hydrogenation reactions and hydrogen fuel cell manufacture. In this presentation we examine the modelling of powder production in a gas atomisation vessel using CFD techniques. In a fully coupled Lagrangian-Eulerian two phase scheme, liquid meal particles are tracked through the vessel following atomisation of a liquid nickel-aluminium stream. There is full momentum, heat and turbulence transport between particles and surrounding argon gas and the model predicts the position of solidification depending on particle size and undercooled condition. Maps of collision probability of particles at different stages of solidification are computed, to predict the creation of satellite defects, or to initiate solidification of undercooled droplets. The model is used to support experimental work conducted under the ESA/EU project IMPRESS.

Investigation of the permeation of model formulations and a commercial ibuprofen formulation in Carbosil® and human skin using ATR-FTIR and multivariate spectral analysis

The purpose of the present study was to use attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and target factor analysis (TFA) to investigate the permeation of model drugs and formulation components through Carbosil® membrane and human skin. Diffusion studies of saturated solutions in 50:50 water/ethanol of methyl paraben (MP), ibuprofen (IBU) and caffeine (CF) were performed on Carbosil® membrane. The spectroscopic data were analysed by target factor analysis, and evolution profiles of the signal for each component (i.e. the drug, water, ethanol and membrane) over time were obtained. Results showed that the data were successfully deconvoluted as correlations between factors from the data and reference spectra of the components, were above 0.8 in all cases. Good reproducibility over three runs for the evolution profiles was obtained. From the evolution profiles it was observed that water diffused better through the Carbosil® membrane than ethanol, confirming the hydrophilic properties of the Carbosil® membrane used. IBU diffused slower compared with MP and CF. The evolution profile of CF was very similar to that of water, probably because of the high solubility of CF in water, indicating that both compounds are diffusing concurrently. The second part of the work involved a study of the evolution profiles of the components of a commercial topical gel containing 5% (w/w) of ibuprofen as it permeated through human skin. Although the system was much more complex, data were still successfully deconvoluted and the different components of the formulation identified except for benzyl alcohol which might be attributed to the low concentrations of benzyl alcohol used in topical formulations. (C) 2009 Elsevier B.V. All rights reserved.

Direct measurement of powder flavor adhesion onto crisp surface using a novel adhesion tester

A new experimental procedure has been implemented and a prototype of a novel adhesion tester has been designed and constructed using rapid prototyping technology. A tumbler mixer has been designed and constructed for coating powder material onto a crisp substrate. In the impact separation experiment, the amount of powder detached from one side of a crisp substrate by the effect of impact forces (48g, 77g, 102g) generated by the tester was measured. Salt particles with different size fractions (63-125, 125-180, and 180-250m) and several flavoring powders have been tested extensively. By plotting the detachment versus impact force, the difference obtained between adhesion strength of different flavoring powders (which is a strong function of particle size and surface oil content of the crisp) has been discussed. The detachment rate of salt particles increased (from 1% to 2%) with particle size (from 63 to 250m) in the presence of oil on the surface of the crisp substrate and decreased rapidly with the increase in the amount of oil applied (from 0 to 1%).

Modelling of a dosator: an analytical approach based on measured powder flow properties

[No abstract is available for this article.]

The application of electrostatic dry powder deposition technology to coat drug-eluting stents

Purpose: A novel methodology has been introduced to effectively coat intravascular stents with sirolimus-loaded polymeric microparticles. Methods: Dry powders of the microparticulate formulation, consisting of non-erodible polymers, were produced by a supercritical, aerosol, solvent extraction system (ASES). A design of experiment (DOE) approach was conducted on the independent variables, such as organic/CO2 phase volume ratio, polymer weight and stirring-rate, while regression analysis was utilized to interpret the influence of all operational parameters on the dependent variable of particle size. The dry powders, so formed, entered an electric field created by corona charging and were sprayed on the earthed metal stent. Furthermore, the thermal stability of sirolimus was investigated to define the optimum conditions for fusion to the metal surfaces. Results: The electrostatic dry powder deposition technology (EDPDT) was used on the metal strut followed by fusion to produce uniform, reproducible and accurate coatings. The coated stents exhibited sustained release profiles over 25 days, similar to commercial products. EDPDT-coated stents displayed significant reduced platelet adhesion. Conclusions: EDPDT appeared to be a robust accurate and reproducible technology to coat eluting stents.

The impact of powder flowing properties on dosator filling system operation

Purpose: To study the impact of powder flow properties on dosator filling systems, with particular focus on improvements in dose weight accuracy and repeatability. Method: This study evaluates a range of critical powder flow properties such as: flow function, cohesion, wall friction, adhesion to wall surfaces, density/compressibility data, stress ratio “K” and gas permeability. The characterisations of the powders considered in this study were undertaken using an annular shear cell using a sample size of 0.5 litres. This tester also incorporated the facility to measure bed expansion during shear in addition to contraction under consolidation forces. A modified Jenike type linear wall friction tester was used to develop the failure loci for the powder sample in conjunction with multiple wall samples (representing a variety of material types and surface finishes). Measurements of the ratio of applied normal stress versus lateral stress were determined using a piece of test equipment specifically designed for the purpose. Results: The correct characterisation of powders and the incorporation of this data into the design of process equipment are recognised as critical for reliable and accurate operation. An example of one aspect of this work is the stress ratio “K”. This characteristic is not well understood or correctly interpreted in many cases – despite its importance. Fig 1 [Omitted] (illustrates a sample of test data. The slope of the line gives the stress ratio in a uniaxial compaction system – indicating the behaviour of the material under compaction during dosing processes. Conclusions: A correct assessment of the bulk powder properties for a given formulation can allow prediction of: cavity filling behaviour (and hence dosage), efficiency of release from dosator, and strength and stability of extruded dose en route to capsule filling Influences over the effectiveness of dosator systems have been shown to be impacted upon by: bed pre-compaction history, gas permeability in the bed (with respect to local density effects), and friction effects for materials of construction for dosators

Using a modified shepards method for optimization of a nanoparticulate cyclosporine a formulation prepared by a static mixer technique

An innovative methodology has been used for the formulation development of Cyclosporine A (CyA) nanoparticles. In the present study the static mixer technique, which is a novel method for producing nanoparticles, was employed. The formulation optimum was calculated by the modified Shepard's method (MSM), an advanced data analysis technique not adopted so far in pharmaceutical applications. Controlled precipitation was achieved injecting the organic CyA solution rapidly into an aqueous protective solution by means of a static mixer. Furthermore the computer based MSM was implemented for data analysis, visualization, and application development. For the optimization studies, the gelatin/lipoid S75 amounts and the organic/aqueous phase were selected as independent variables while the obtained particle size as a dependent variable. The optimum predicted formulation was characterized by cryo-TEM microscopy, particle size measurements, stability, and in vitro release. The produced nanoparticles contain drug in amorphous state and decreased amounts of stabilizing agents. The dissolution rate of the lyophilized powder was significantly enhanced in the first 2 h. MSM was proved capable to interpret in detail and to predict with high accuracy the optimum formulation. The mixer technique was proved capable to develop CyA nanoparticulate formulations.

A methodology for characterising new lead-free solder paste formulations used for flip-chip assembly applications

The paper reports on the investigation of the rheological behaviour new lead-free solder pastes formulations for use in flip-chip assembly applications. The study is made up of three parts; namely the evaluation of the effect of plate geometry, the effect of temperature and processing environment and the effect of torsional frequencies on the rheological measurements. Different plate geometries and rheological tests were used to evaluate new formulations in terms of wall slip characteristics, linear viscoelastic region and shear thinning behaviour. A technique which combines the use of the creep-recovery and dynamic frequency sweep tests was used to further characterise the paste structure, rheological behaviour and the processing performance of the new paste formulations. The technique demonstrated in this study has wide utility for R & D personnel involved in new paste formulation, for implementing quality control procedures used in paste manufacture and packaging and for qualifying new flip-chip assembly lines