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.]

Raman spectroscopy in pharmaceutical analysis

A wide and versatile range of analytical techniques are routinely used, indeed are necessary, in pharmaceutical analysis. Over the past decade Raman spectroscopy has increasingly come to the fore as a valuable member of the arsenal of methods used, from both a fundamental and applied perspective, for the interrogation of solid, liquid and solution phase samples. Advances have occurred not only in instrumentation but also in fundamental techniques and applications. The method holds substantial potential for the investigation of, what are normally considered, problematic or challenging areas of analysis. The aforementioned areas include – but are, definitely not limited too reaction kinetics, pharmaceutical drug discovery, detection of counterfeit/adulterated/illegal drugs, trace analysis and uses for on-line pharmaceutical process manufacturing. This, the first of several articles on the use of Raman spectroscopic techniques in pharmaceutical analysis, provides an introductory overview of the theory of the technique.

Vibrational spectroscopic studies of the structure of di-amino acid peptides. Part II: cyclo(L-Asp-L-Asp) in the solid state and in aqueous solution

Solid-state protonated and N,O-deuterated Fourier transform infrared (IR) and Raman scattering spectra together with the protonated and deuterated Raman spectra in aqueous solution of the cyclic di-amino acid peptide cyclo(L-Asp-L-Asp) are reported. Vibrational band assignments have been made on the basis of comparisons with previously cited literature values for diketopiperazine (DKP) derivatives and normal coordinate analyses for both the protonated and deuterated species based upon DFT calculations at the B3-LYP/cc-pVDZ level of the isolated molecule in the gas phase. The calculated minimum energy structure for cyclo(L-Asp-L-Asp), assuming C-2 symmetry, predicts a boat conformation for the DKP ring with both the two L-aspartyl side chains being folded slightly above the ring. The C=O stretching vibrations have been assigned for the side-chain carboxylic acid group (e.g. at 1693 and 1670 cm(-1) in the Raman spectrum) and the cis amide I bands (e.g. at 1660 cm(-1) in the Raman spectrum). The presence of two bands for the carboxylic acid C=O stretching modes in the solid-state Raman spectrum can be accounted for by factor group splitting of the two nonequivalent molecules in a crystallographic unit cell. The cis amide II band is observed at 1489 cm(-1) in the solid-state Raman spectrum, which is in agreement with results for cyclic di-amino acid peptide molecules examined previously in the solid state, where the DKP ring adopts a boat conformation. Additionally, it also appears that as the molecular mass of the substituent on the C-alpha atom is increased, the amide II band wavenumber decreases to below 1500 cm(-1); this may be a consequence of increased strain on the DKP ring. The cis amide II Raman band is characterized by its relatively small deuterium shift (29 cm(-1)), which indicates that this band has a smaller N-H bending contribution than the trans amide II vibrational band observed for linear peptides.

IR/Raman spectroscopy and DFT calculations of cyclic di-amino acid peptides. Part III: comparison of solid state and solution structures of cyclo(L-Ser-L-Ser)

B3-LYP/cc-pVDZ calculations of the gas-phase structure and vibrational spectra of the isolated molecule cyclo(L-Ser-L-Ser), a cyclic di-amino acid peptide (CDAP), were carried out by assuming C-2 symmetry. It is predicted that the minimum-energy structure is a boat conformation for the diketopiperazine (DKP) ring with both L-Beryl side chains being folded slightly above the ring. An additional structure of higher energy (15.16 kJ mol(-1)) has been calculated for a DKP ring with a planar geometry, although in this case two fundamental vibrations have been calculated with imaginary wavenumbers. The reported X-ray crystallographic structure of cyclo(L-Ser-L-Ser), shows that the DKP ring displays a near-planar conformation, with both the two L-Beryl side chains being folded above the ring. It is hypothesized that the crystal packing forces constrain the DKP ring in a planar conformation and it is probable that the lower energy boat conformation may prevail in the aqueous environment. Raman scattering and Fourier-transform infrared (FT-IR) spectra of solid state and aqueous solution samples of cyclo(L-Ser-L-Ser) are reported and discussed. Vibrational band assignments have been made on the basis of comparisons with the calculated vibrational spectra and band wavenumber shifts upon deuteration of labile protons. The experimental Raman and IR results for solid-state samples show characteristic amide I vibrations which are split (Raman:1661 and 1687 cm(-1), IR:1666 and 1680 cm(-1)), possibly due to interactions between molecules in a crystallographic unit cell. The cis amide I band is differentiated by its deuterium shift of ~ 30 cm(-1), which is larger than that previously reported for trans amide I deuterium shifts. A cis amide II mode has been assigned to a Raman band located at 1520 cm(-1). The occurrence of this cis amide II mode at a wavenumber above 1500 cm(-1) concurs with results of previously examined CDAP molecules with low molecular weight substituents on the C-alpha atoms, and is also indicative of a relatively unstrained DKP ring.

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

Modelling of dosator operation for improved manufacturing performance

Purpose: To develop an improved mathematical model for the prediction of dose accuracy of Dosators - based upon the geometry of the machine in conjunction with measured flow properties of the powder. Methods: A mathematical model has been created, based on a analytical method of differential slices - incorporating measured flow properties. The key flow properties of interest in this investigation were: flow function, effective angle of wall friction, wall adhesion, bulk density, stress ratio K and permeability. To simulate the real process and (very importantly) validate the model, a Dosator test-rig has been used to measure the forces acting on the Dosator during the filling stage, the force required to eject the dose and the dose weight. Results: Preliminary results were obtained from the Dosator test-rig. Figure 1 [Omitted] shows the dose weight for different depths to the bottom of the powder bed at the end of the stroke and different levels of pre-compaction of the powder bed. A strong influence over dose weight arising from the proximity between the Dosator and the bottom of the powder bed at the end of the stroke and the conditions of the powder bed has been established. Conclusions: The model will provide a useful tool to predict dosing accuracy and, thus, optimise the future design of Dosator based equipment technology – based on measured bulk properties of the powder to be handled. Another important factor (with a significant influence) on Dosator processes, is the condition of the powder bed and the clearance between the Dosator and the bottom of the powder bed.

Tailoring the morphology of WO₃films with substitutional cation doping: Effect on the photoelectrochemical properties

With the aim of improving the performance and extending the range of applications of mesoporous WO₃films, which were initially developed for the photoelectrochemical oxidation of water, we investigated the effect of a number of dopants (lithium, silicon, ruthenium, molybdenum and tin) upon the transparency, crystallinity, porosity and conductivity of the modified films. Tin, molybdenum and silicon were shown to improve the electrochromic behaviour of the layers whereas ruthenium enhanced considerably the electronic conductivity of the WO₃films. Interestingly, most of the dopants also affected the film morphology and the size of WO₃nanocrystals. X-ray photoelectron spectra revealed absence of significant segregation of doping elements within the film. Raman analyses confirmed that the monoclinic structure of WO₃films does not change upon substitutional cation doping; thus, the crystallinity of WO₃films is maintained.

The role of space charge formation in the generation of thermally stimulated current (TSC) spectroscopy data for a model amorphous drug system

Thermally stimulated current (TSC) spectroscopy is attracting increasing attention as a means of materials characterization, particularly in terms of measuring slow relaxation processes in solid samples. However, wider use of the technique within the pharmaceutical field has been inhibited by difficulties associated with the interpretation of TSC data, particularly in terms of deconvoluting dipolar relaxation processes from charge distribution phenomena. Here, we present evidence that space charge and electrode contact effects may play a significant role in the generation of peaks that have thus far proved difficult to interpret. We also introduce the use of a stabilization temperature in order to control the space charge magnitude. We have studied amorphous indometacin as a model drug compound and have varied the measurement parameters (stabilization and polarization temperatures), interpreting the changes in spectral composition in terms of charge redistribution processes. More specifically, we suggested that charge drift and diffusion processes, charge injection from the electrodes and high activation energy charge redistribution processes may all contribute to the appearance of shoulders and 'spurious' peaks. We present recommendations for eliminating or reducing these effects that may allow more confident interpretation of TSC data.

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.

Practical solvent system selection for counter-current separation of pharmaceutical compounds

Counter-current chromatography (CCC) is a technique that shows a lot of potential for large scale purification. Its usefulness in a "research and development" pharmaceutical environment has been investigated, and the conclusions are shown in this article. The use of CCC requires the development of an appropriate solvent system (a parameter of critical importance), a process which can be tedious. This article presents a novel strategy, combining a statistical approach and fast HPLC to generate a three-dimensional partition coefficient map and rapidly predict an optimal solvent system. This screen is performed in half a day and involves 9 experiments per solvent mixture. Test separations were performed using that screen to ensure the validity of the method.

Diameter-selective solubilization of carbon nanotubes by lipid micelles

The one-step dispersion of HiPco single-walled carbon nanotubes in aqueous media with the use of a synthetic lyso-phosphatidylcholine was studied. Solubilization occurs through wrapping of lipid molecules around the circumference of the tubes, yielding lipid monolayers on the graphitic sidewalls as evidenced by atomic force microscopy imaging and dynamic light scattering measurements. Raman spectroscopy showed that the dispersion and centrifugation process leads to an effective enrichment of the stable aqueous suspension in carbon nanostructures with smaller diameters.

Cyclic voltammetry and spectroelectrochemical study of nickel and cobalt diphenyltetraazaannulene complexes

The absorption spectra. cyclic voltammetry and spectroelectrochemistry of [Ni(II)DPTAA] and [Co(II)DPTAA] (DPTAA = 6,13-diphenyldibenzo[b,i][1,4,8,11] tetraaza[14]annulene) complexes in DMF are reported in detail. The ligand oxidation is observed for [Ni(II)DPTAA] at +0.70 V vs. SCE whereas Ni2(+/+) occurs at - 1.60 V. For [Co(II)DPTAA], a ligand oxidation redox couple is seen at +0.56 V while the Co2+/+ and Co2+/3+ redox couples appear at -1.21 and +0.24 V, respectively. All observed redox couples are assigned to reversible one-electron processes on account of peak separations and scan-rate dependency. These processes were further investigated by spectroelectrochemistry for [Co(II)DPTAA]. For [Co(II)DPTAA], axial ligation of pyridine was found to shift the Co2+/3+ redox couple more negative. while the ligand oxidation was shifted to more positive potentials. From a spectrophotometric titration of [Co(II)DPTAA] with pyridine an equilibrium constant, K-f, was determined for the binding of pyridine to [Co(II)DPTAA]. This was found to be 10.2 dm(3) mol(-1), slightly lower than that of [Co(II)TAA], indicating the influence of the phenyl groups. From this value and shifts in the Co2+/3+ redox couple upon ligation, an equilibrium constant for the binding of pyridine to [Co(III)DPTAA], K'(f), was found to be 5.06 x 10(6) dm(3) mol(-1). (c) 2007 Elsevier B.V. All rights reserved.

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.

Comparisons between “sand blast” and “centripetal effect accelerator” type erosion testers

There are two major types of erosion testing devices that are used throughout the world for quantifying particle impact erosion against a solid surface. The first of these uses pressurised air to accelerate abrasive particles through a nozzle so that they impinge upon a target specimen. The second adopts a rotating disc to accelerate abrasive particles using the centripetal effect so that they impinge upon a series of targets arranged around the periphery of the disc. This paper reports the findings of a collaborative project that was designed to compare the performance and results obtained from a rig of each of the two types mentioned above. The sand blast type rig was provided by The Department of Powder Science Technology (POSTEC) at The Telemark Technological Research and Development Centre (TEL-TEK), Porsgrunn, Norway while the centripetal effect accelerator was provided by The Wolfson Centre for Bulk Solids Handling Technology, University of Greenwich, London, UK. The test programme included tests against a wide range of materials that are commonly used in pneumatic handling facilities. (Pneumatic handling is a means of conveying and transporting powders and granular solid materials in bulk in industrial process plant, through pipelines using a gas as the carrier medium.) Olivine sand was used as the abrasive and it was projected against the test specimens at velocities and concentrations commensurate with those seen in pneumatic conveyors. In all instances the materials used in the test programme were taken from the same batch so that scatter of experimental results due to specimen variation was minimised. The paper contains a series of recommendations for erosion testing equipment. A discussion based on the results and their applicability to the prediction of wear in pneumatic conveyors concludes the paper.