Diffusion

Diffusion the movement of particles in a solid from an area of high concentration to an area of low concentration, resulting in the uniform  distribution of the substance 

Diffusion refers to the process by which molecules intermingle as a result of their kinetic energy of random motion. Consider two containers of gas A and B separated by a partition. The molecules of both gases are in constant motion and make numerous collisions with the partition.

Diffusion is process which is NOT due to the action of a force, but a result of 

the random movements of atoms (statistical problem)

Osmosis

Osmosis is the spontaneous net movement of solvent molecules through a semipermeable membrane into a region of higher solute concentration, in the direction that tends to equalize the solute concentrations on the two sides. It may also be used to describe a physical process in which any solvent moves across a semipermeable membrane (permeable to the solvent, but not the solute) separating two solutions of different concentrations. 

           

Tonicity

 Tonicity is a measure of the effective osmotic pressure gradient (as defined by the water potential of the two solutions) of two solutions separated by a semipermeable membrane. In other words, tonicity is the relative concentration of solutions that determine the direction and extent of diffusion.

------------------

Steady state diffusion

 Fick’s first law of diffusion

For steady-state diffusion condition (no change in the system with time), the net flow of atoms is equal to the diffusivity Dtimes the diffusion gradient dC/dx

Non-Steady-State Diffusion

In practice the concentrationof solute atoms at any point in the material changes with time–non-steady-state diffusion

For non-steady-state condition, diffusion coefficient, D- NOT dependent on time

PROCEDURES AND APPARATUS

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.

Simple diffusion cell.

 (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.

The  permeability cell .

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.