Example Reports

Below is a selection of the type of work undertaken in the medical device industry.

CSMA Report Summaries Relating to Medical Devices

Surface Analysis of Blemishes on the Inner Surfaces of Aluminium Metered Dose Inhaler (MDI) Cans The purpose of this work was to investigate the appearance of blemishes on the inner surface of aluminium MDI cans. Surface analysis of the blemishes suggests that the stain is a water drying stain. It was shown that the area of interest was rich in calcium, sodium and chlorine. Analysis of a Stain on the Outer Surfaces of Aluminium Metered Dose Inhaler (MDI) Cans The aim of this work was to analyse a stain on the outer surface of an MDI can. XPS and ToF-SIMS were used to characterise the stain. Analysis showed the stain to be organic in nature, characterised by a series of compounds which were based on fatty acids and found in lubricating oils. Investigation into the Molecular Weight Distribution of a Fluorocarbon Coating on Barrels of a Metered Dose Inhaler (MDI) The aim of this work was to analyse fluorocarbon-coated MDI barrels after partial silver metallisation in order to determine the molecular weight distribution. ToF-SIMS analysis showed: Depositions of sub-monolayer levels of silver for silver cationisation experiments were successful. For the three-sputter deposition times, 0.5 s, 1 s and 2 s, the fluorocarbon coating was only partially covered. As expected, the silver coverage increased with the deposition time. The coating is consistent with an oxygenated fluorocarbon material. There is also evidence for the incorporation of nitrogen-containing species on/in the fluorinated surface. There is clear evidence for interaction between the deposited silver and the oxygenated fluorocarbon coating, there is no evidence for high mass fluorocarbon-based cations giving rise to an oligomer distribution pattern. Analysis of Metered Dose Inhaler (MDI) Barrels The aim of this investigation was to analyse, un-used, filled and ex DTU MDI barrels using XPS and ADXPS. Surface analysis showed: There was significant silicone contamination of some of the barrel surfaces. The silicone is thought to originate from the lubricant, which is applied to the barrel assembly during construction/filling. Generally there is a clear decrease in fluorine concentration with increasing analysis depth for all the barrels. However, the size of the decreases relative to the overall concentrations are marginal but do represent a ‘thinning’ of the coating. In general the angle dependent data shows a gradual, almost linear, transition between fluoro-carbon character and substrate character which would suggest a diffuse structure rather than a discrete layer of fluoro-carbon on the substrate No significant trend in CF3:CF2 ratio is found for changes in sampling depth or for the different barrel conditions for any particular batch. Surface Characterisation of Plasma Fluorinated Polymer Metered Dose Inhaler (MDI) Barrels The aim of this investigation was to characterise the surface of plasma fluorinated polymer MDI barrels. XPS and Imaging DSIMS analysis has showed: Layer thicknesses for all samples typically lie in the range 2nm - 4nm. Although the coating is thin it is notably uniform and complete despite the fact that the barrels are substantially roughened by machinery. There is no significant correlation of thickness with feed gas or treatment time. One sample showed distinct areas of relative F- depletion. An XPS investigation of Discoloration and “Rusting” on Metered Dose Inhaler (MDI) Stem Samples This study was commissioned to determine if the brown deposit was in fact rust and to investigate the cause of the other discoloration. The XPS investigation showed: Significant differences in surface composition and chemistry. Boron, probably as nitride, was detected after annealing, suggesting boron impurity in the steel. There was significant evidence that the brown deposit was rust resulting from corrosive attack by saline (sodium/potassium chloride) material. There was evidence for iron oxidation and growth of a surface chromium oxide film. A large concentration of organic material was also present on the discoloured surfaces. Analysis of Inhaler Blends Surface analysis of inhaler blends by DSIMS imaging, to monitor the relative distribution of active drugs and carriers. DSIMS mass spectral and image data identified: Particles of carrier A were identified. Drugs Y & Z were identified on the surface of particles of carriers A & B Analysis of the Contents of Inhalers using ToFSIMS and XPS This work was carried out to determine the presence or otherwise of fluorocarbon species within the contents of inhalers. ToFSIMS and XPS investigations showed: Oxygenated fluorocarbon material was detected from the residues of one set of samples only. For these samples the metering chamber and can have a fluorocarbon coating. Silicone is deposited for all samples and has been attributed to a lubricant used during the assembly of the metered dose inhalers. XPS Analysis of “Brown Blemishes” on an Aluminium Inhaler Cans The aim of this work was to investigate the occurrence of Brown blemishes believed to be organic residues on an aluminium inhaler can. An XPS investigation showed: The discoloration in the blemishes does not appear to be due to superficial organic contamination since there is as much carbonaceous material off the blemished region as there is on the stain and the stain is not affected by ultrasonic cleaning in acetone. The presence of sodium and chlorine, albeit at low levels, may indicate that a corrosion mechanism is involved in the formation of the blemishes. An XPS Investigation of Active Loading on Drug Powders for Dry Powder Inhalers (DPIs) The aim of this work was to investigate the potential of surface analysis using XPS for measuring directly the active loading at the surface of DPI powders, and for investigating chemical interactions between the active drug species and the lactose carrier. The XPS investigation showed: The surface compositions of the reference components were in good agreement with their chemical formulae. The compositions of the drugs were measured and the relative fractions of the three components derived. It was not possible to distinguish between the two populations of drug from these XPS data alone. The ratio of sulfur to fluorine was found to be very variable in the drugs. Investigation into the Leakage of a Metered Dose Inhaler The aim of this work was to investigate the cause of a leakage of a metered dose inhaler. ToFSIMS and XPS investigations concluded: The large spot of white deposit on the valve gasket is considered to be the symptom of the inhaler leakage problem, not the cause. Leakage is attributed to the presence of an aluminium/aluminium-rich flake on the valve gasket prior to sealing of the inhaler unit. This resulted in localised damage of the softer gasket surface, compromising the seal integrity with subsequent leakage of contents. DSIMS Analysis of an Orthopaedic Implant The aim of this work was to investigate the presence and depth distribution of silicon on an orthopaedic implant. DSIMS analysis concluded: Silicon is apparently present on and within the coating. However, the major contribution to this silicon level is from areas of exposed substrate. Silicon is therefore present within the chromium - cobalt alloy or is present at the coating / alloy interface as a contaminant. Analysis of Contamination on a Femoral Knee Joint This work was commissioned in order to ascertain the origin of a greasy stain over the entire polished surface of a femoral knee joint that had been vacuum packed in a heat sealed polymer bag. XPS and ToFSIMS analysis concluded: Most of the stain material on the knee joint is unfunctionalised, saturated hydrocarbon-based. There is a significant amount of silicone and sodium on both the polished knee joint surface and the heat shrink-wrapped polymer bag surface with which it was in contact. There are also traces of sulphur, chlorine and calcium which are typical of detergents that have been dispersed in domestic tap water. In contrast, there is only polymer, erucamide slip agent and other additives on an unused bag surface. It is thought possible that the detergent contamination has arisen because the knee joint may have been wrapped whilst still damp or contaminated after the washing/cleaning treatments used. There is evidence that the level of hydrocarbon contamination is higher in the areas of the surface of the knee joint which are in intimate contact with the wrapper. This suggests that the origin of the contamination is the polymer material itself and the high levels of hydrocarbon material contaminant on the surface correspond to degradation product from the packaging resulting from application of heat during sealing or irradiation. Surface Analysis of Two Knee Implants The aim of this work was to investigate the surface composition of two knee implants. ToFSIMS and XPS analysis showed: The surfaces of both implants exhibited high levels silicone. Species attributable to the implant alloy were also detected indicating that the silicone overlayer was less than 5nm thick or patchy Traces of other species, including Al, Ca, Na and a range of organic contaminants, were also detected. A LIMA Investigation of Brown Stains on Shot Blasted Prosthesis Components The aim of this work was to analyse a brown stain on knee femoral and hip joint components. LIMA analysis concluded: The bulk alloy contains titanium and aluminium. The brown deposit consists of a material, which contains sodium, potassium, calcium, aluminium, chlorine and traces of iron in an organic matrix. The matrix consists of long chain hydrocarbons including amine (and possibly amide) - like compounds, possibly also with carboxylic acid functionality. DSIMS Analysis of Drug X Containing Polymer-Coated Stents The purpose of this investigation was to carry out SIMS depth profile analysis from the coating surface through to the stent substrate, in order to monitor the relative concentration of drug X through the coating. DSIMS analysis of the coated stents has shown: Evidence for a significant variation in the individual and total coating layer thicknesses, indicating variable deposition rates for the basecoat and the topcoat. The presence of drug X within the topcoat of the initial sample. Exposure to the release medium produces an elution of drug X from the basecoat into the topcoat layer. Progressive removal of the topcoat with a consequent large reduction in the total coating thickness from ~21µm initially to ~5µm after 20 days in the release medium. Evidence of ion exchange DSIMS Analysis of Six Coated Stents The purpose of this study was to compare the layer thickness, integrity and layer structure of the coatings. The SIMS depth profile analysis of the six stents showed: All stent coatings have a layer structure The coating thicknesses appear to vary widely suggesting that the amounts of materials retained on the stents are variable. Several stents showed evidence for unevenness of coating or defects present in the structure. Visual inspection of these stents by optical microscopy confirms the presence of some cracks in the layer coating structures. All stents show the presence of the base PC layer, applied before drug loading. The variability of coating thicknesses coupled with the evidence for unevenness of coating and the presence of defects may lead to variation in drug elution rates in vivo. DSIMS Analysis of Drug –Coated Stents The aim of this investigation is to determine the depth distribution of the drug X and to measure the overall thickness of the coating. The conclusions of this study are as follows: With reference to the nominal loadings of PC and drug applied to the stents, the coating thicknesses appear to vary widely suggesting that the amounts of materials retained onto the stent surfaces are very variable. There was evidence in the depth profiles of the majority of the stents for unevenness of the coatings and possibly cracks and exposed substrate areas. For the cap-coated stents only one sample appeared to show a 3-layer structure, as intended. In all cases, there was evidence of a phosphate-rich layer on the stent surface which may have resulted from storage / treatment of the bare stents prior to coating deposition or preferential migration to the coating / stent interface after coating deposition. The wide variability of the coating thicknesses with respect to the loadings of materials applied to the stents, together with the unevenness of the coatings and presence of defects are likely to be strong contributing factors for the uncontrolled elution rates observed for this set of stents. An XPS Investigation of Silane Deposition on Stents This work was commissioned to investigate the deposition of silane on stents by a series of processes. The analysis showed: All of the treated stents exhibit increased concentrations of silicon and chlorine. The Si:Cl ratio is only slightly greater than 1:1 in most cases, suggesting that the majority of the silicon detected is chloropropyl silane not silicone contamination. Low levels of ionic chloride species are also present on two stents, indicating a direct reaction between the metallic stent surface and the acid. Since the metallic stent elements are readily detectable in all cases, the silane coatings are either patchy, or form a continuous layer less than ~8 nm thick. A comparison of the data indicates no major difference between using xylene and methanol/water solutions. Investigation into the Effect of Processing on the Surface of Stainless Steel Stents The aim of this investigation was to determine quantitatively the chemical composition of the surface of the stents and to monitor the depth distribution of key species within the near surface region until steady state composition was achieved. In all cases the overall thickness, to the metallic bulk of stent wires (i.e. the sum of the top three layers in the schematic above) was no more than approximately 25nm. There were significant quantitative differences in the surface compositions of the stents. The phosphate concentration was greatest on the stent which had been electro-polished only, with no further processing. This stent also displayed the lowest concentration of organic material at the surface. The phosphorus concentrations on the stent which had had the modified electro-polishing treatment was significantly smaller, by greater than a factor of three for the phosphorus. The lowest phosphorus concentration was found on the stent from the finished device. This stent was notable for a large surface enrichment in chromium compared to the other stents Furthermore, the negative ion depth profiles showed that all samples, except one, showed a chromium oxide to be on top of the iron oxide layer, in the metal oxide region. An XPS Investigation of the Effects of the Cleaning Procedures and Curing Conditions on Silane Layer Deposition on Stents The aim of this work was to investigate the effects of varying the cleaning conditions on four stents. This investigation concluded: All the stent surfaces contained tantalum, oxygen, carbon, silicon, sodium and sometimes a trace of chlorine. The chlorine is presumably a residue from the trichlorovinylsilane treatment chemical. The data are consistent with a silane based overlayer (containing silicon, carbon and oxygen) on top of a metallic tantalum substrate with a thin oxide layer. The different cleaning procedures have not had a significant effect on the thickness of the oxide film on the tantalum. Comparison of the three areas on each stent shows only small differences in silicon concentration between them. Thus there appears to be good coating uniformity between the three 4mm by 1mm areas probed by spectroscopy. The imaging analysis also suggests reasonable coating uniformity on the 10µm scale, with no uncoated patches visible. The average silicon concentrations are smaller on the extensively cleaned stents compared to the normally cleaned stents, but there is no significant difference in Si concentration between the two stents cured under different conditions for either cleaning method.