This presentation summarizes a recent study conducted at Alfred University that examined the corrosion of glass vials using a modified version of the hydrolytic resistance test. Vials made from converted glass tubing were filled with increasing incremental volumes of WFI and then autoclaved. The recovered liquid was analyzed for shifts in pH and the extractables were measured using ICP-OES. The results support the hypothesis that the heel region is a primary contributor to corrosion of glass vials made from converted tubing.

1. Fill volume as an indicator of surface
heterogeneity in glass vials
Matthew M. Hall, Associate Professor of Biomaterials & Glass Science
Kazuo Inamori School of Engineering at Alfred University
E-mail: hallmm@alfred.edu

2. The interior surface of a glass vial can be non-
uniform due to manufacturing processes
Image taken from Stevanato Group web site
Condensation
Volatilization
Diffusion
Intense, localized heating during the conversion process can lead to modifications of the glass vial
surface through a combination of possible mechanisms, including mass transport driven by thermal
gradients, evaporation of volatile species, and condensation of vapors on the interior surface.
Glass vials produced from converted tubing experience the greatest heating in the heel and shoulder.
The altered surface chemistry of these regions can potentially impact properties, including chemical
stability.

3. Standard tests for evaluating chemical stability are
an average measure of the glass vial surface
Test medium is in contact with
the shoulder, body, and heel
regions in standard hydrolytic
resistance tests
Standard hydrolytic resistance tests are quite useful for identifying drifts in a manufacturing
process, but they may be of limited use for assessing the chemical stability of glass vials
since the primary regions of interest (heel and shoulder) represent a minority of the interior
surface.
In this study, we evaluated a simple modification to the standard hydrolytic resistance test.
Vials were filled with incrementally increasing volumes of WFI to assess the possible
heterogeneity of the interior surface.

4. Hypothesis: The heel region is a primary contributor to
corrosion processes with converted glass vials
Experiment:
- Nine vial types made from converted glass tubing were obtained from four
different manufacturers
- Vials were a mixture of 33 and 51 expansion Type I glass
- None of the vials were subjected to a sulfate dealkalization treatment
- One of the vial types (#6) was from a lot that failed the standard hydrolytic
resistance test
- One of the vial types is an amber glass
- Each vial type was incrementally filled with WFI in volumes ranging from
~0.5 mL up to near maximum fill capacity using a semi-automated filling
system (Watson-Marlowe, Flexicon FF15)
- Five samples were prepared for each fill volume/vial type condition
- Filled vials were autoclaved at 121 C for 1 h
- Recovered liquid (called “conditioned WFI”) was measured for pH using a
combination glass electrode and extractables using ICP-OES

5. 8.5
The pH of conditioned WFI is 1
dependent on fill volume 2
8.0 3
Mean pH generally decreases 4
with increasing fill volume 5
7.5 6
Vial type that failed the hydrolytic 7
resistance shows elevated pH 8
7.0
over the entire range 9
Mean pH
Behavior suggests that elevated 6.5
pH at low fill volumes is due to
enhanced sensitivity of the heel
region to corrosion 6.0
Decrease in mean pH with
5.5
increasing fill volume is due to a
dilution effect
5.0
Interesting to note that some vial
types may show evidence of
increased corrosion near the 4.5
shoulder region 0 2 4 6 8 10
Fill Volume (mL)

6. Extractables results support
1.0
hypothesis about heel region
In general, highest level of
0.9
extractables observed for lowest fill
volumes; increasing fill mostly dilutes
Correlation Coefficient
the contribution of the heel region
0.8
Highest levels of extracted sodium
correlated with highest levels of
0.7 p=
extracted silicon 0.00586
Spearman rank correlation analysis
0.6
demonstrates varying pattern of
dissolution behavior as a function of
fill volume p = 0.0141 Al-B Al-Na Al-Si
0.5
- p value for all tested pairs
<<0.001 except where noted p = 0.0791 B-Na B-Si Na-Si
- Analysis performed on extractables
data sampled from increasing fill 0.4
volume ranges ≤1 ≤2 ≤4 ≤ 10
- Change in correlation coefficients
for aluminum pairs implies that Fill Volume Range (mL)
corrosion behavior is a function of
fill volume

7. 3.0
Extractables results support
hypothesis about heel region
(continued)
2.5
Ratio-based analysis of extractables
B:Na Molar Ratio in Conditioned WFI
results also supports non-uniform
corrosion behavior
2.0
For example, the figure to the right
plots the molar ratio of B:Na in
conditioned WFI versus fill volume 1.5
Horizontal line would be observed if
corrosion behavior was independent 1.0
of fill volume
No clear pattern observed amongst
the various vial types, but non-linear 0.5
1 2 3
behavior is clearly 4 5 6
observed, particularly for fill volumes 7 8 9
less than approximately 4 mL 0.0
0 2 4 6 8 10
Fill Volume (mL)

8. Conclusions
• Results of this study indicate that the heel region of vials made from converted
glass tubing can be more susceptible to corrosion
• Mean pH of conditioned WFI generally decreases with increasing fill volume
• Highest level of extractables generally observed for lowest fill volumes; increasing
fill volumes dilute species extracted from the heel region
• Correlation analysis and ratio-based analysis of extractables data shows that
pattern of dissolution behavior varies depending on fill volume
• Caveats:
• Surface area-to-volume ratio changes as a function of fill volume
• Geometry of vials can vary depending on vial type
• Condensate formation on upper region of vial during autoclaving could be a
potential contributor to corrosion
• Results should not be taken as an indicator of relative performance of
various vial types
Matthew M. Hall, Associate Professor of Biomaterials & Glass Science
Kazuo Inamori School of Engineering at Alfred University
E-mail: hallmm@alfred.edu