Pharmaceutical Manufacturing Handbook: Production and

PHYSIOLOGY AND CHARACTERISTICS OF HUMAN SKIN 797
5.11.2.1 Transepidermal Water Loss and Occlusion
Transepidermal water loss (TEWL) is a natural occurrence that takes place in the
skin layers. TEWL is the result of movement of water from the deep skin layers
across the epidermis into the outside atmosphere. It is a tightly regulated process
that is controlled by the stratum corneum [9] . Occlusive topical bases and devices,
such as transdermal patches, block TEWL and cause increased hydration of the skin.
Hydration of the skin increases the permeation rates of compounds transdermally.
The occluding effect of transdermal patches is an important mechanism that
promotes increased diffusion of the compound across the skin into the systemic
circulation [10] .
5.11.2.2 Skin Lipids
As keratinocytes differentiate and move toward the stratum corneum, they synthesize
an abundance of lipids, much of which are packaged into small organelles called
lamellar granules [11] . When reaching the stratum corneum, the corneocytes eject
these lipid granules forming a principal component of the brick - and - mortar structure
of the stratum corneum. Lipids synthesized in the skin layers are thought to
arrive from carbon sources derived from acetate obtained from the systemic circulation.
The role of epidermal lipids in the brick - and - mortar structure of the stratum
corneum and the barrier function of the skin is well established in the literature
[12] . Many studies have suggested that when organic solvents such as dimethyl
sulfoxide (DMSO) are used to dissolve epidermal lipids, an increase in skin permeability
is found [13] .
The major lipids found in the stratum corneum are ceramides, fatty acids, and
cholesterol. Free fatty acids make up 10 – 15% of the lipid mass of the stratum
corneum and predominantly consist of straight - chain saturated species ranging from
14 to 28 carbons in length. Cholesterol, a major lipid found in the stratum corneum,
represents approximately 25% of the total stratum corneum lipid while cholesterol
sulfate accounts for another 5%.
Ceramides are considered to be the largest group of lipids found in the stratum
corneum, representing 50% of the total lipid weight. Six distinct ceramide fractions
have been isolated and characterized [14] . Ceramide 1 is derived from the linoleate
- rich acylglucosylceramide. Ceramide 2 consists of straight - chain saturated fatty
acids amide linked to sphingosine and dihydrosphingosine bases. Ceramide 3 consists
of saturated fatty acids amide linked to phytosphingosine, which has an additional
hydroxyl group on carbon 4. Ceramides 4 and 5 both consist of α - hydroxyacids
amide linked to sphingosines and dihydrosphingosines. Ceramide 6 contains α -
hydroxyacids amide linked to phytosphingosines.
It has been suggested that these ceramides form a gel - phase membrane domain
within the skin. Straight fatty acid chains as well as the small polar head groups on
the ceramides are thought to produce a tightly packed domain which is less fl uid
and thereby less permeable than other liquid crystalline domains which are also
present. Recent evidence using differential scanning calorimetery (DSC) and infrared
absorption spectroscopy analyses verifi es the presence of gel phases within the
stratum corneum.