Physical pharmacy Dr. Khaled Sh.

Shamareekh
Lectures (3)

Diffusion

Diffusion is the basic mechanism of mass transport of individual molecules of a substance. This
transport is a result of random motions of the molecules.

Diffusion processes in pharmaceutics include:

(i) transport of drug out of controlled-release formulations,

(ii) transport of drug molecules across biological barriers (absorption, distribution,…)
(iii) diffusion of such as oxygen and water vapor into and out of drug product containers.

Drug transport across a polymeric barrier

Drug transport through a polymeric or biological barrier may occur by simple molecular
permeation known as molecular diffusion or by movement through pores and channels
known as pore diffusion (Figure below).

(a) Diffusion through the homogeneous membrane, (b) diffusion through solvent (usually water)-filled
pores, and (c) diffusion through the fibrous membrane strands.
Physical pharmacy Dr. Khaled Sh. Shamareekh
Lectures (3)

Molecular diffusion

It is the transport of the drug molecule through a membrane that involves dissolution of the
drug in the matrix of the membrane, followed by its diffusive transport to the surrounding
bulk liquid.

This diffusion depends on: 1) the size the molecules, 2) their solubility in the membrane matrix,
3) their partition coefficient between the matrix and the liquid, and 4) the degree of stirring.

Pore diffusion

Pore diffusion involves passage of drug through the solvent-filled pores in the membrane. The
release of drug depends on: 1) porosity of the membrane and 2) surface functional groups
(e.g., hydrophobic or hydrophilic).

Principles of diffusion

Fick’s laws of diffusion quantitate the amount of solute diffusing per unit time and area as a
function of concentration gradient of solute in the direction of diffusion.

 Fick’s First Law of Diffusion

Fick’s first law of diffusion describes the amount flux (J) of material across unit area of a barrier
(membrane) over time.

Flux (J) is proportional to the driving force, i.e., the concentration gradient across the
membrane. Therefore, the expression of Fick’s first law of diffusion is given below:
 Physical pharmacy Dr. Khaled Sh. Shamareekh
Lectures (3)

Where: D is the diffusion coefficient of a penetrant, in cm2/s

C is the concentration, in g/cm3 or g/mL
x is the distance perpendicular to the surface of the barrier, in cm

D is the diffusion coefficient and it changes depending on: the properties and composition of
the diffusion medium, temperature, pressure, and the nature of material.

 The negative sign in the equation indicates that the movement of material is from the
higher to lower concentration.

Fick’s first law of diffusion describes the diffusion process under steady state when the
concentration gradient (dC/dx) does not change with time. Diffusive transport from a
solid dosage form is usually slow, leading to most of the drug transport happening under
steady-state conditions.

Diffusion-controlled drug delivery systems

The polymeric material is chosen in such a way that drug diffusion through the macromolecular
network is the rate-limiting step. These systems are called “diffusion controlled.” There are
three types of diffusion-controlled drug delivery systems (Figure below): reservoir systems,
monolithic systems, and miscellaneous systems.

 Reservoir Systems

The drug and the release rate–controlling material (generally a polymer or lipid) are physically
separated. The drug is the core of the dosage form “reservoir” and the polymer network
surrounds this reservoir “release rate–controlling membrane.”
Physical pharmacy Dr. Khaled Sh. Shamareekh
Lectures (3)

Two types of systems can be distinguished:

 Reservoir devices with non-constant activity source: the initial drug concentration is below
drug solubility. Consequently, the drug concentration at the inner side of the release rate–
controlling membrane decreases with time, resulting in decreasing drug-concentration
gradients. This results in release of drug by first-order kinetics.

 Reservoir devices with constant activity source: the initial drug concentration is greater than
drug solubility. Hence, dissolved and undissolved drugs coexist within the reservoir.
Therefore, the released drug molecules are replaced by dissolution of undissolved drug,
leading to constant drug-release rates (zero-order kinetics).
Physical pharmacy Dr. Khaled Sh. Shamareekh
Lectures (3)

 Monolithic Systems

The drug and matrix former are not clearly physically separated (homogeneous matrix). Two
types of devices can be distinguished:

 Monolithic solutions: in which the drug is molecularly dispersed within the matrix former.
This type is highly suitable for poorly water-soluble drugs. Dispersion of the drug molecules
within a polymeric matrix avoids the dissolution step and might enhance the bioavailability.

 Monolithic dispersions, which contain both dissolved and dispersed drug.

 Miscellaneous Systems

This can be a coated pellet, capsule, or tablet, containing the drug in the core as well as in the
coating layer.