X-ray photoemission spectrography (XPS) was used to analyze the surface of several pieces of the companies vials to determine delamination.  Using XPS, one obtains a surface analysis of the outermost 1-5nm of a solid sample.  An atomic percentage was measured for carbon, oxygen, silicon, aluminum, sodium, calcium, magnesium, nitrogen, and other trace elements (<0.5%) for each sample.  Only vials of Company A and B were analyzed by this technique.  The results show that many of these vials are delaminating.                     

From table 1, findings show: sample 10 is a reference (clean) vial from Company B which was unexposed to the drug;  sample 5 is from Company B (4˚C/4 week) that was a clean area of the vial, but had been exposed to the drug;  samples 1-6, and 9 are from Company B;  samples 7 and 8 are from Company A.

The highlighted band in Table 1 is the reference vial (Sample 10).  In comparing the other samples to sample 10, results indicate that the atomic percent of the more soluble elements (Na, Ca, Mg) associated with glasses were high from the norm, while silicon was low from the norm, which could be related to glass delamination exposing fresh glass.  Another significant change is that carbon is going up and oxygen is going down, which is likely an organic residue.

Samples 1 (30˚C/4 week) and 2 (40˚C/8 week) had the brown residue.  This was difficult to determine, but since carbon and the more soluble elements go up and oxygen and silicon go down a possible result could be residue from product or cleaning.

Sample 6 (25˚C/4 week) has the striations; the more soluble elements are high, which suggests delamination exposing fresh glass.   It is possible that the striations were there in manufacturing and etched away more with increasing time and temperature.

Sample 9 (55˚C) results suggest delamination.

Samples 7 and 8 (55˚C) have the dark and pinkish residue which seems similar to delamination; these results suggest delamination.

Can pitting constitute delamination? We have learned pitting occurs frequently and is common with delamination flakes.  A vial not related to these studies, but of similar type, was sent out to a company that measures 3D surface texture.  Their definition of surface texture measurement is derived from a measurement of the heights of the various image points.  The following pictures show parameters and profiles of pitting on the vial’s base, neck, and center.  Figure 28 shows the base area of the vial.  If the X and Y axes are visualized, they cross over certain pitting along the surface.  The blue area is a larger pit which results in ~100-200nm on the colored scale and then in the horizontal profile it can be determined that the depth is ~150nm.  If the whole picture is looked at, the 3D image shows the blue areas spiking down from the surface.   

click image to enlarge (815K) FIGURE 28

Figure 29 shows the base of the vial again with everything a lot clearer.  This picture shows a larger pit and the horizontal profile shows more depth and again a stronger 3D image.  We can speculate that as these pits grow larger and/or appear in greater number, they can begin to form a flat surface resulting in the flaky appearance that becomes glass delamination.

click image to enlarge (792K) FIGURE 29

Figures 30 and 31 show measurements from the center and neck of the provided vial; both seem to have fine pitting.  The data from these diagrams of surface texture measurements suggest a relation between pitting of a vial and glass delamination of a vial.

click image to enlarge (428K) FIGURE 30

click image to enlarge (408K) FIGURE 31

In summary, time and temperature studies provide good evidence that as time and temperature increase delamination increases.  There is a correlation between delamination and the type of drug the vial contains; and another correlation of delamination occurring in the area that is common to the fill-line.  These correlations can be more readily determined when vials contain the drug solution so that they can be looked at, recorded, and filtered under cleanroom conditions.  XPS results infer when delamination occurs; silicon goes down while the other soluble elements go up exposing a new layer of glass.  There are also significant changes from a clean unexposed vial to an exposed vial.  Pitting is still questionable, but common, when delamination occurs and surface measurement analysis provides positive data. 

A special thanks to McCrone Associate staff members, Scott Stoeffler for the SEM images and IR data, Kent Rhodes for the XPS data, and Mark Bukantis for the surface texture measurement information.