Filtration and Filters
Filtration is used to remove particles from solutions. These particles might
be particulate matter or they may be microorganisms. Filtration is not a "terminal
sterilization" procedure as are steam (moist heat), dry heat, ionized radiation,
or gas sterilization. Filtration will sterilize the product, but after filtration,
the sterile product is then aseptically combined with its packaging. Filtration
is used for materials that are chemically or physically unstable if sterilized
by heat, gas, or radiation.
There are two types of filters, depth filters
and membrane filters.
Depth filters are seldom used for sterilization. They are constructed of randomly
oriented fibers or particles (e.g., diatomaceous earth, porcelain, asbestos)
that have been pressed, wound, or otherwise bonded together to form a tortuous
pathway for flow. The microorganisms are either entrapped in the path or adsorbed
to the filter material. The random structure of material inside the filter creates
fluid flow pathways that can vary from extremely narrow to very wide. Filter
materials can also break off or come loose during filtration and appear in the
filtrate.
Depth filters are rigid enough to filter a solution being pulled into a syringe.
They can also be used to filter a solution being pushed out of a syringe. But
the same filter cannot be used to draw up and then expel a solution. A new needle
is required before pushing the solution out of the syringe. If the solution
is expelled through the original filter needle, the solution will be re-contaminated.
Screen
filters have a continuous uniform structure that consists of fixed size pores.
Particles that are larger than the pore openings cannot pass through the filter
and are retained on the surface of the filter. The amount of material retained
by a screen filter is limited by the surface area of the filter. Screen filter
pore sizes can be predetermined and precisely controlled during manufacturing.
View a video demonstration on how to use filters on syringes
The most common screen filter used in compounding is called a "membrane
filter." In terms of structure, membrane filters are thin microporous sheets
made from a variety of plastics. Membrane filters must have a nominal pore size
of 0.22 microns or less if they are to be used for sterilization. However, membrane
filters are available in a wide range of pore sizes from 0.11 to 10 microns.
Membrane filters are intended to filter a solution
only as it is expelled from a syringe. If a solution
is to be drawn into a syringe and then filtered through a membrane filter, use
the following procedure:
- A regular needle (or a depth filter needle) is attached
to the syringe.
- The solution is pulled into the syringe.
- Air bubbles are removed from the syringe.
- The needle is removed from the syringe.
- A membrane filter unit is then attached to the syringe.
- A regular needle is placed on the needle end of the
filter.
- Air is eliminated from the filter chamber by holding
the syringe in a vertical position so that the needle is pointing upward.
Air must be expelled before the filter becomes wet; otherwise, the air will
not pass through the filter.
- Once air has been expelled, pressure should be slowly
and continuously applied to push the solutions through the filter.
View a video demonstration on how to use a
membrane filter
Membrane filters also eliminate the risk of air embolism. Once a membrane filter
is wet, air cannot pass through it unless the "bubble point pressure"
of the filter is exceeded. "Bubble point pressure" for a 0.22 micron
membrane filter is approximately 55 psi, a pressure that will not occur during
parenteral administration. So any air that enters the administration set will
be stopped at the filter surface and not allowed to enter the patient's body.
The same bubble point pressure is used in another way. After a filter is used,
the integrity of the filter can be determined if the wetted filter is exposed
to a high pressure. If the filter is intact, the appearance of bubbles on the
filter surface should occur when the pressure is about 50 - 55 psi. However,
if the filter integrity has been compromised, the bubble point pressure will
be much lower.
Membrane filters are often packaged in a round plastic holder which can easily
be attached to the end of syringes. Some filters are attached to administration
sets and serve as "final filters" and filter the solution immediately
before it enter the patient's vein. Some administration sets have filters already
built into the set. Filters can also be placed inside of needles; these are
called "filter needles." There
are double ended filter needles which is a simple unit that has a filter between
two needles. This allows solution transfer directly from one container to another
container and eliminates the need of using a syringe to transfer the solution.
Filters are also supplied as single membrane units to be used in specialized
filtration apparatus.
Several things must be considered when selecting a
membrane filter. Hydrophilic filters are easily wetted and are used
for aqueous solutions. Hydrophobic filters repel water but allow solvents such
as alcohol and air to pass. So these filters would be used to sterilize solutions
containing alcohol or isopropyl alcohol, or as air filters. Other considerations
include the volume capacity of the filter, how much pressure can be applied
to the filter without damaging its integrity, and what is the filter's compatibility
or adsorption profile for the material being filtered.
The material to be filtered also requires some considerations.
Viscous oils can be filtered, but it is a time consuming process. Heating the
oil will reduce its viscosity and make filtration easier. Some powders can also
be filtration sterilized by first dissolving the powder in a solvent, filtering
the resultant solution, and then evaporating the solvent under aseptic conditions.
Consideration must also be given to the sterilization
of containers, closures, and apparatus. A non-sterile surface that
comes in contact with a sterilized product will render the product non-sterile.
These contact surfaces must also be pyrogen-free. The temperatures and times
necessary for depyrogenation are substantially greater than those for sterility.
It will probably be necessary to depyrogenate containers, closures, and apparatus
separately from the formulation and then aseptically combine them.
