Several filter geometries are available to perform sterile filtration.
STERILE FILTRATION
Several
filter geometries are available to perform sterile filtration. These consist of
flat membranes in a stainless steel press (<0.293 m), pleated membranes
housed in stainless steel cartridges, and stacked plates in the form of flat seg-ments
of membrane filters.
Matrix
filters consist of fibers with pores having a depth of up to 1.2 x 10-4
m. Cellulose nitrate may be dissolved in the highly volatile solvents amyl acetate,
ether, and dioxane. A gel-forming solvent, acetone, ethanol, or propanol, may
be added. The mixture is poured on a flat plate and placed in a
controlled-temperature environment to dry. Pore size is dependent on the
gel-forming solvent concentration. A number of other substances may be used as
filter material. These include other cellulose esters, acetate and butyrate;
polyamides (nylon); polysulfones; fluorocarbons (Durapore membranes),
poly-vinylidenedifluoride (hydrophobic) or surface modified with organic amides
(hydrophilic); acrylic polymers; and polyvinyl chloride. To make some
mem-branes hydrophilic, surfactants may be added including Tween 80, Triton
X-100, hydroxypropyl cellulose, and glycerol. Sieve filters are made of
polycarbonate (nucleopore 10 5 m thick). Collimated uranium fission
products form nucleation tracks in film. Etching chemical exposure determines
pore size.
Most
membrane filters, when wetted, have negative charge. Bacteria have a similar
negative charge and do not necessarily remain on the filter. Filters with other
characteristics can be selected under these circumstances. Positively charged
(AMF Zeta Plus Membrane) or protein- and peptide-adsorbing (Pall Posidyne Nylon
66) filters can be selected.
Ionic
strength, pH, pressure, and flow rate all effect adsorption of particles. The
flow rate through a filter is described in equation (1).
where
Ci is the inherent resistance of the filter to flow (a function of void
volumes), A is the surface area, P is the pressure, and V is the viscosity.
Filters
are related according to nominal pore size and absolute pore size (the largest
pore in the filter). This recognizes that a pore size distribution exists.
The
filter integrity can be evaluated by a number of techniques. The destructive
test involves filtering a suspension of bacterial cells (Pseudomonas diminuta,
0.3 x 10-6 m) through a 2 x 10-7 m filter. Six liters of
suspension containing 1 x 1010 org/L grow up on an agar plate.
Downstream of a 10-6-m filter, there should be nothing and an 8-log
reduction would have occurred. The bubble point test assumes that pores can be
characterized as capillaries. When totally wetted, all the capillaries should
be full of water or solution. The pore length is generally much greater than
the diameter. Pressure is applied to the wetted filter. The bubble point
pressure (P) may be described as follows:
where
γ is the surface
tension (7.2 N/m2), θ is the contact angle, and D is the diameter of
capillary.
The bubble point
test is performed before and after sterile filtration.
A
specified area of filter must be soaked in a specified volume of product for a
designated time. The accelerated stability of a product in the presence of a
filter can be performed at 313 to 333 K for 60 days. The extent of damage,
nature and quantity of extractables, and potency of active ingredients must be
evaluated prior to selection of a filter for a particular process.
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