RATIONALE OF THE FLOW DECLINE METHOD
The flow decline, or flow decay method, is used to determine the effective filtration area required to process an entire batch
of any volume in an acceptable time frame under a given delta (Δ) pressure. It is managed by a simple arithmetical proportioning.
A small filter with a known effective area is used to measure the volume of a drug preparation that can be processed at a
selected ?P (differential pressure), given the rate of flow and the throughput it produces. The ratio of the filtration area
to the sample volume is extrapolated to the filter area required to process an entire batch. The simplicity of the test ensures
its easy mastery; its performance demands only a modest technical background.
In a flow decline experiment, a small aliquot of the suspension is filtered through a small filter. The retained particulate
load accumulates on the filter pores, successively diminishing filter porosity and the flow rate. At a certain point, the
flow is judged to have ceased for all practical purposes; the effort and time that would be spent obtaining additional filtrate
beyond that point is not economically feasible.
In these experiments, one measures the flow rate (volume over time), the throughput, and the total filtrate volume obtained
over the duration of the filtration.5 The ambient temperature is also noted. The results identify the ratio between the EFA and the volume of filtrate that is
produced before the filtration is terminated. The numerical value has a significance beyond that inherent in the specific
filter. Rather, it is taken to quantify the capacity of filters of that type to retain the maximum amount of particulate matter
present in that unique fluid preparation under the given filtration conditions. Its importance is in the nature of a validation
exercise.
An arithmetical extrapolation of the experimentally obtained ratio can then be used to determine how large a filter area will
be required to process a batch of product.6 The ratio that is established is:
in which X (m
2
) is the filter area required to process the batch.
The required filter area, thus calculated, can then be translated into the number and lengths of cartridges or other filtration
devices one wishes to use for the batch operation, by using additional equations. The area of a flat disc filter is:
A =π ÷4 × d
2
The 47-mm disc has an area of 17.4 cm2 (1.49 in2 ). A 10-in cartridge composed of the same filter polymer will be assumed to contain an area of 6 ft2 . (The areas of other filter cartridges may be calculated in the same way.) Therefore, the throughput volume of the cartridge
relative to that of a 47-mm filter of the same polymeric composition is:
Thus, if the 47-mm disc yields a total throughput of 2,500 mL, then 2.5 L x 580 = 1,450 L (~383 gallons) will flow through
the cartridge before it shuts down. The rate of flow measured on the 47-mm disc then indicates the number of 10-inch cartridges
with an EFA of 6 ft2 that would be required to complete the batch filtration in a timely manner at the constant differential pressure, temperature
being kept constant.
From the foregoing, it should be self-evident that the accuracy of the arithmetical extrapolation is highly dependent on the
accuracy of the EFA attributed to the 47-mm disc. Nevertheless, it is in this very matter that many incorrect assumptions
are made.
ACCURATELY MEASURING THE EFFECTIVE FILTER AREA OF A 47 MM FLAT DISC FILTER
In the classical application of the flow decline method, a 47-mm membrane is removed from its package and inserted into a
stainless steel holder, where it is held in position by the compressive action of an O-ring. The area of a 47-mm filter disc
is 17.4 cm2 . In the holder, however, the O-ring pre-empts a certain quantity of the disc's peripheral space by clamping down on the
filter disc to prevent edge-leakage. This reduces the filtration area available for filtration. Thus, the EFA of the inserted
47-mm disc is reduced to less than 17.4 cm2 .
The actual EFA of such an assembly was measured by filtering a staining solution of acridine yellow or Coomassie blue (Figure
2). The stained area identified the sealed area in the confines of the O-ring. As can be seen, the staining solution did not
extend beyond or under the O-ring. The stained area measured 41 mm in diameter, which has a total area of 13.2 cm2 . Thus, of the 7.4 cm2 area of the 47-mm disc filter, 4.2 cm2 were rendered unavailable for filtration by the O-ring's preemptive sealing action.
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