A number of
experimental methods and diffusion cells have been reported in the literature.
Examples of those used mainly in pharmaceutical and biologic transport studies
are introduced here.
Cells of simple
construction, such asthe one reported by
Karth et al. are probably best for diffusion work.
They are made of glass or clear plastic, are
easy to assemble and clean, and allow visibility of the liquids and rotating
stirrer.
They may be thermostated
and lend themselves to automatic sample collection and assay. The donor chamber
is filled with drug solution.
Samples are
collected from the receptor compartment in an automatic fraction
collector and subsequently assayed spectrophotometrically.
Experiments may be
run for hours under these controlled conditions.
Biber and Rhodes constructed a
Plexiglas threecompartment diffusion cellfor use with either synthetic or
isolated biologic membranes.
The drug was,
allowed to diffuse from the two outer donor compartments in a central receptor
chamber.
Results were
reproducible and compared favorably with those from other workers.
The three-compartment
design created greater membrane surface exposure and improved analytic sensitivity.
The permeation
through plastic film of water vapor and of aromatic organic compounds from
aqueous solution may,be investigated in two-chamber glass cells similar in
design to those used for
studying drug solutions in
general.
Nasim et al. reported
on the permeation, of aromatic compounds from aqueous. solution through polyethylene
films.
Higuchi and Aguiar studied
the permeability of water vapor through enteric coating materials using a glass
diffusion celland a McLeod gauge to measure changesin pressure across the film.
(After M. G. Karth, W. I. Higuchi and J. L.
Fox, J. Phann. Sci. 74, 612, 1985,
reproduced with permission of the copyright owner.)
Diffusion cell
for permeationthrough stripped skin layers.
The penneant may be
in the form of a gas, liquid, or gel. Key:A, glass stopper; B, glass chamber;
C, aluminum collar; D, membrane and sample holder. (From D. E. Wurster, J. A.
Ostrenga and L. E. Matheson, Jr., J. Pharm. Sci. 68, 1406, 1410, 1979,
reproduced with permission of the copyright owner.
The sorption of
gases and vapors may be determined by use of a microbalance enclosed in a
temperature controlled and evacuated
vessel that is capable of weighing within a sensitivity of ±2 x 10-6 g. The gas
or vapor is introduced at controlled pressures into the glass chamber containing the polymer or
biologic film of known dimensions,
suspended on one arm of the balance. The mass of diffusant sorbed at
various pressures by the film is recorded directly.
The rate of approach
to equilibrium sorption permits easy calculation of the diffusion coefficients
for gases and vapors. In studying percutaneous absorption, animal or human
skin, ordinarily obtained by autopsy, is employed.
Scheuplein"
described a cell for skin penetration experiments
made of Pyrex and consisting of two halves,
adonor and a receptor chamber, separated by a sample of skin supported on a
perforated plate and securely clamped in place.
The liquid in the
receptor was stirred by a Teflon-coated bar magnet.
The apparatus was
submerged in a constant-temperature bath, and samples were removed periodically
and assayed by appropriate means.
For compounds such as steroids, penetration
was slow, and radioactive methods were found necessary to determine the low
concentrations. Wurster et al. developed a permeability cell to study the diffusion through stratum corneum
(stripped from the human forearm) of various permeants, including gases,
liquids, and gels.
During diffusion
experiments it was kept at constant temperature and gently shaken in the plane
of the membrane.
Samples. were
withdrawn from the receptor chamber at definite times
and analyzed for the permeant. The kinetics and equilibria of liquid and solute absorption
'into plastics, skin, and chemical and
other biologicmaterials may be determined simply by placing sections of the
film in a constant-temperature bath of the pure liquid or solution. The
sections are retrieved at various times, excess liquid is removed with
absorbant tissue, and the film samples are accurately weighed in tared weighing
bottles. A radioactive-counting technique also may be used with this method to analyze
for drug remaining in solution and, by
difference, the amount sorbed into the film.
. Partition coefficients are determined simply by equilibrating the drug
between two immiscible solventsin a suitable vessel at a constant temperature
and removing samples from both phases, if possible, for analysis.
Addicks et al described
a new flow-through cell, Grass and Sweetana" proposed a diffusion cell for
the study of gastrointestinal permeation, and Addicks et al designed a cell
that yields results more comparable to
the diffusion of drugs under
clinical conditions. Equilibrium solubilities of drug solutes are also' required
in diffusion studies.
