The Relationship among Pore-Size Ratings, Bubble Points, and Porosity - Pharmaceutical Technology

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The Relationship among Pore-Size Ratings, Bubble Points, and Porosity

Pharmaceutical Technology

In performing the bubble-point measurement, a water-filled membrane is suitably positioned and retained in a holder so that a progressively increasing air pressure can be directed against its upstream face. It is assumed that membrane pores act like simple, round capillaries in their imbibition of water and in their being emptied under a differential pressure. The water filling the pores prevents frank air passage until the applied air pressure becomes large enough to expel the blocking water from the widest pores. The passage of air then escaping through the vacated passageways is evidenced by the appearance of bubbles in a downstream pool; hence the term "bubble point."

The vacating of the liquid by an imposed air pressure represents a work function, namely, a forced separation, (removal) of the wetting liquid from the polymer surface (40). The bubble-point pressures reflect the various strengths of the bonding interactions between different polymers wet by different liquids. The air pressure needed to separate the water molecules from the pore walls, as occurs upon emptying the pores, quantifies the work function involved. A given polymer type with different liquids, or a given liquid paired with various polymeric type membranes, results in bonds of different strengths and is different as well for each pore size.

Thus, different bubble points (delta pressures) quantify the force expelling the wetting liquid from the pores. Pore-size ratings, were they but assessable, could be applied to all filter types. The rating of whatever pore size, were it to represent the dimensions of a passageway, would not change with the filter type. As stated, however, the bubble-point value, presumably for the same size pore, is different for each polymer–liquid couple—whether for each polymeric membrane with different liquids or for a given liquid with different type filters. Rating filters by bubble-point values peculiar to each solid–liquid couple of each membrane type and to each pore size would be too cumbersome to be practical.

In practice the membrane is measured by bubble point, which is then rather arbitrarily translated into a pore size rating. The translation rests on a conjunction of two items: FDA defined a sterilizing filter as being one that withstands the challenge of 1 107 cfu of B. diminuta per square centimeter of EFA. In addition, several experimenters found that an inverse straight-line relationship existed between the log reduction values and the bubble-point levels for the various polymeric-type membrane filters. The higher the bubble point, the smaller the restricted pore diameter and the greater the LRV value (see Figure 8) (41). One could, therefore, read from a graph the bubble-point value of a given filter–liquid couple that would correspond to the LRV of a "sterilizing" membrane.

Figure 8: Microbe retention to bubble point.
The corresponding bubble-point value (using the same liquid) would, however, be different for each of the various polymeric-type membranes. But the value, however different for each type membrane, would identify a "sterilizing filter" as defined by FDA's approved 1 107/cm2 challenge. It could differ as well for organisms for which B. diminuta may not be a model.

Integrity test values used in membrane making

In casting the polymer solution in the form of a wet-film preparatory to its conversion to a finished, dry microporous membrane, the manufacturer seeks to predict by periodic testing in the wet casting-state the properties that will eventuate in the dried, finished product. Essentially, what is sought in the wet stage is the foretelling of the proper integrity test value of the finished dry filter. The considerable complexities of the solvent evaporation, washing, and drying stages of the fabrication process are involved in negotiating the change from casting solution to dry membrane. The translation of the characteristics of the wet cast film into those of the dry membrane requires a considerable experience in producing membranes.


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