Editorial Feature

Demonstrating Surface Analysis Techniques to Resolve Problems with Inhalers

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The aim of this article was to study the emergence of blemishes on the inner surface of aluminum MDI cans. Surface analysis of the blemishes proposed that the stain was a water-drying stain and it was demonstrated that the region of interest was abundant in sodium, calcium, and chlorine.

Analysis of a Stain on the Outer Surfaces of Aluminum Metered Dose Inhaler (MDI) Cans

The objective of this research was to examine a stain on the outer surface of an MDI can.

The stain was characterized using ToF-SIMS and XPS techniques. Analysis confirmed the stain to be organic in nature, characterized by a range of compounds that were based on fatty acids and present in lubricating oils.

Investigation into the Molecular Weight Distribution of a Fluorocarbon Coating on Barrels of a Metered Dose Inhaler (MDI)

The objective of this research was to examine fluorocarbon-coated MDI barrels following partial silver metallization in order to establish the molecular weight distribution.

ToF-SIMS analysis revealed:

  • Depositions of sub-monolayer levels of silver for silver cationization experiments were effective. The fluorocarbon coating was just partially covered for the three-sputter deposition times—0.5 second, 1 second, and 2 seconds. As predicted, the silver coverage improved with the deposition time.
  • There is an obvious proof for the interaction between the oxygenated fluorocarbon coating and the deposited silver; however, there is no proof for high mass fluorocarbon-based cations yielding an oligomer distribution pattern.
  • The coating is observed to be consistent with an oxygenated fluorocarbon material. There is also proof for incorporating nitrogen-containing species on/in the fluorinated surface.

Analysis of Metered Dose Inhaler (MDI) Barrels

The objective of this study was to analyze filled, unused, and ex DTU MDI barrels with the help of the ADXPS and XPS techniques.

Surface analysis demonstrated:

  • There was considerable silicone contamination of certain barrel surfaces. The silicone is assumed to arise from the lubricant, which is applied to the barrel assembly at the time of construction/filling.
  • Usually, there is an apparent reduction in fluorine concentration with an increase in the analysis depth for all the barrels. However, the decreased size in relation to the overall concentrations is trivial but do represent a ‘thinning’ of the coating.
  • On the whole, the angle-dependent data demonstrates a slow, nearly linear, transition between substrate character and fluoro-carbon character, which would imply a diffuse structure instead of a discrete fluoro-carbon layer on the substrate
  • There is no considerable trend in CF3:CF2 ratio for variations in sampling depth or for the different barrel conditions for any specific batch.

Surface Characterization of Plasma Fluorinated Polymer Metered Dose Inhaler (MDI) Barrels

The objective of this analysis was to define the surface of plasma fluorinated polymer MDI barrels.

XPS and Imaging DSIMS analysis has demonstrated that:

  • While the coating is thin, it is remarkably uniform and complete despite the fact that the barrels are considerably roughened by machinery
  • Layer thicknesses for all samples normally fall between 2 and 4 nm
  • One sample exhibited discrete regions of relative F-depletion
  • There is no important link between thickness and feed gas or treatment time

An XPS investigation of Discoloration and “Rusting” on Metered Dose Inhaler (MDI) Stem Samples

This investigation was assigned to identify whether the brown deposit was indeed a rust, and to analyze the origin of the other discoloration.

The XPS investigation exhibited:

  • Considerable variations in surface chemistry and composition
  • Boron, possibly as nitride, was detected after annealing, indicating the impurity of boron in the steel
  • There was noteworthy proof that the brown deposit was rust produced as a result of corrosive attack by saline (potassium/sodium chloride) material
  • There was evidence for oxidation of iron and development of a surface chromium oxide film; a significant concentration of organic material was also found on the discolored surfaces.

Analysis of Inhaler Blends

Surface analysis of inhaler blends by DSIMS imaging was carried out to supervise the relative distribution of active drugs and carriers.

In the DSIMS mass spectral and image data:

  • Particles of carrier A were identified
  • Y and Z drugs were identified on the surface of particles of carriers A and B

Analysis of the Contents of Inhalers using ToFSIMS and XPS

This research was performed to determine the presence of fluorocarbon species within the contents of inhalers.

ToFSIMS and XPS investigations:

  • Enabled the detection of oxygenated fluorocarbon material from the residues of one set of samples alone. For these samples, the metering chamber can be coated with fluorocarbon.
  • Enabled the application of silicone to all samples and this has been ascribed to a lubricant employed during the assembly of the metered dose inhalers

XPS Analysis of “Brown Blemishes” on an Aluminum Inhaler Cans

The objective of this research was to examine the occurrence of brown blemishes thought to be organic residues on an aluminum inhaler can.

An XPS study revealed:

  • The discoloration in the blemishes does not seem to be caused by superficial organic contamination, because the amount of carbonaceous material off the blemished region is equivalent to that on the stain and the stain is not impacted by ultrasonic cleaning in acetone.
  • The presence of chlorine and sodium—although at low levels—may denote that a corrosion mechanism is involved in the development of the blemishes.

An XPS Investigation of Active Loading on Drug Powders for Dry Powder Inhalers (DPIs)

The objective of this study was to examine the potential of surface analysis using XPS for the direct measurement of active loading at the surface of DPI powders, and for analyzing chemical interactions between the lactose carrier and the active drug species.

The XPS analysis demonstrated that:

  • The surface compositions of the reference components were in line with their chemical formulae
  • The drugs’ compositions were measured and the relative fractions of the three components were calculated
  • Distinguishing between the two populations of drug was impossible from these XPS data alone
  • The ratio of sulfur to fluorine was found to be extremely unstable in the drugs

Investigation into the Leakage of a Metered Dose Inhaler

The objective of this study was to examine the cause of a leakage of a metered dose inhaler.

ToFSIMS and XPS analysis concluded that:

The large spot of white deposit on the valve gasket is the symptom of the inhaler leakage issue, not the cause. Leakage is ascribed to the presence of an aluminum/aluminum-rich flake on the valve gasket before sealing the inhaler unit. This led to localized impairment of the softer gasket surface, affecting the seal integrity with subsequent leakage of contents.

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