Drugs and the pharmaceutical sciences

14 Quigley
FIGURE 15 Depth and membrane filters incorporated into a filtration step prior to crystallization
of the Active Pharmaceutical Ingredients.
prefiltration, before the liquid is permitted to encounter the final, sterilizing microporous
membrane filter. Otherwise, premature clogging of that filter will occur.
The purpose of the pretreatments is to present large surface areas on which adsorption
and impurity retention may occur. Hence, the use of fumed silica, a finely divided
particulate material especially suited for removing lipids and lipoproteins (Condie and
Toledo-Perreyra, 1976). The depth-type prefilters likewise offer large surface areas for
impurity depositions, e.g., fiberglass prefilters. Additionally, however, prefilters consisting
of mixed esters of cellulose coatings on paper (cellulose fiber mats) promote purifying
adsorptive sequestrations through hydrogen bonding to their nitro group moiety, as stated
above. Positive charge modified depth filters are especially suitable as prefilters in serum/
plasma prefiltration. They offer positive-charged sites for particle capture, as well as large
surface areas for particle adsorption. In consequence, asbestos filters, previously used
extensively, are now at least partially successfully substituted for with success by the charge
modified depth filters (Holst et al., 1978).
Pretreatment Agents
Fiore et al. (1980) describe successful applications of pretreatments and prefiltrations
relative to therapeutic blood protein preparation. Fumed silica and DE are used as
pretreatment aids. The fumed silica (degussa aerosil) has a surface area of 200 m 2 /g,
diatomite a surface area of approximately 2 m 2 /g. Condie and Toledo-Pereyra (1976)
advise that lipoproteins, triglycerides, cholesterol, fibrinogen, and the plasminogenplasmin
system present in 1 l of plasma are adsorbed onto 40 g of fumed silica within a
contact time of 60 min. This is significant, because Olson and Faith (1978) report that
lipoproteins serve to clog microporous filters. Similarly, fibrinogen has a clogging action
on such membranes, particularly as it may form fibrous deposits of fibrin in the operation
of the blood-clotting mechanism. The adsorptive preremoval of these substances renders
more practicable subsequent filtration of plasma/serum. Diatomite has long been utilized
in the pretreatment of plasma (Cohn et al., 1946). Depending on how heavily laden the
plasma/serum is, how difficult it is to filter, from 2.5 to 5 g are used per liter of the liquid.
Removal of the silica or diatomite can be effected in several ways, such as by filtration
utilizing prefilters of the type herein discussed. The efficiency of such “filter aid”
pretreatments is judged by the clarity of the plasma/serum filtrate as determined by
nephelometry (Cohn et al., 1946; Holst et al., 1978).
Prefliters for Plasma/Serum
As stated in Chapter 2, the development of positive charge modified prefilters permitted
the replacement of asbestos filters for the prefiltrative purification of plasma/protein, the