Establishing Material Compatibility, Process Conditions, and Bubble Points of Filters - Pharmaceutical Technology

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Establishing Material Compatibility, Process Conditions, and Bubble Points of Filters
The authors explain the factors that can cause a failure in a bubble-point integrity test and what to consider when a product-specific bubble point must be defined.


Pharmaceutical Technology


Conclusion


Table VII: Effect of preservative-containing solutions and Biopharm tubing on the bubble point. (IMAGE IS COURTESY OF MERCK & CO.)
These studies demonstrated that the type of tubing selected for filter-sterilizing an antimicrobial preservative-containing formulation may affect the filter's postuse product bubble point. In the case of platinum-cured silicone tubing, bubble-point failures were caused by the presence of poly(dimethyl) siloxane, or silicone oil, trapped on the filter membrane (4). The presence of poly(dimethyl) siloxane was detected using Fourier transform infrared spectroscopy (4). The lowering of the bubble point was confirmed by readdition of poly(dimethyl) siloxane in a separate recirculation study (4). The lowering of the bubble points resulted from a reduction in the surface tension of the liquid that was wetting the membrane pores. For example, it has been previously demonstrated that silicone oils have low surface tensions (6). The surface-tension reduction was caused by the adsorption of polydimethyl siloxane to the filter membrane. The lower surface tension caused the gas to pass through the pores of the filter more easily, resulting in lower bubble-point values. The following items must be considered when determining the product-specific bubble point of a filter for sterilizing parenteral drugs:
  • Materials that have product contact, specifically those upstream of the filter, should be tested to determine if they affect the bubble point. If the materials are found to suppress the bubble point, a material screening-procedure should be used to identify those that have the least effect on the bubble point.
  • When selecting tubing material that will be in contact with product that contains preservatives, consider the length of time that the product will be in contact with the different materials, including the filter, during the manufacturing process. Incorporate the processing time into laboratory studies for determining the product-specific bubble point (7).

Brian K. Meyer* is a research fellow, and Diego Vargas is a senior engineer, both at Merck & Co., 770 Sumneytown Pike, West Point, PA 19486, tel. 215.652.3992, fax 215.652.5299,

*To whom all correspondence should be addressed.

References

1. M. Russell and T.H. Meltzer, "An Interpretation of the Pharmaceutical Industry Survey of Current Sterile Filtration Practices," PDA J. Pharm. Sci. Technol. 52 (6), 337–339 (1998).

2. FDA, Guideline on Sterile Drug Products Produced by Aseptic Processing (Rockville, MD, 1987).

3. Parenteral Drug Association, "Technical Report No. 26: Sterilizing Filtration of Liquids," PDA J. Pharm. Sci. Technol. 52 (S-1) (1998).

4. B.K. Meyer and D. Vargas, "Impact of Tubing Material on the Failure of Product-Specific Bubble Points of Sterilizing-Grade Filters," PDA J. Pharm. Sci. Technol. 60 (4), 1–6 (2006).

5. B.K. Meyer et al., "Antimicrobial Preservative Use in Parenteral Products: Past and Present," J. Pharm. Sci. 96 (12), 3155–3167 (2007).

6. T. Svitova et al., "Wetting Behavior of Silicone Oils on Solid Substrates Immersed in Aqueous Electrolyte Solutions," Langmuir 18 (18), 6821–6829 (2002).

7. B.K. Meyer and D. Vargas, "Impact of Tubing Material on the Failure of Product-Specific Bubble Points of Sterilizing-Grade Filters," presented at the National PDA Conference, Colorado Springs, CO, April 2008.


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