Pharmaceutical Manufacturing Handbook: Production and

796 TRANSDERMAL DRUG DELIVERY
containing nicotine on their clothes or skin. Nicotine, because of its physical and
chemical properties, is low molecular weight and has excellent transdermal penetration,
and signifi cant blood levels can lead to many adverse reactions, such as nausea
and vomiting [6] .
5.11.2
PHYSIOLOGY AND CHARACTERISTICS OF HUMAN SKIN
The skin is the largest organ in the human body and has many physiological functions.
The skin serves to regulate overall body homeostasis, protect the body from
external pathogens and chemicals, as well as control water loss from the body. The
skin has three main layers. The epidermis, which is the outermost layer, is the thinnest
layer of the skin and provides the most signifi cant barrier function [7] . Beneath
the epidermis, the dermis provides mechanical support to the skin and the third
layer, immediately under the dermis, is a layer of subcutaneous fat called the
hypodermis.
The epidermis consists of fi ve principal layers and is an area of both intense biochemical
activity and differentiation. These layers are the stratum corneum, stratum
lucidum, stratum granulosum, stratum spinosum, and stratum basale. The stratum
corneum (horny layer) is the uppermost layer of the epidermis and the skin. The
stratum corneum is composed of dead keratinocytes, which are called corneocytes,
and has an abundance of keratin and lipid structures [8] . The stratum corneum is
considered the rate - limiting barrier for the diffusion of chemical compounds across
the skin. The stratum lucidum (clear layer) is composed of two to three layers of
dead fl attened keratinocytes which appear translucent under a microscope and are
present only in thick glabrous skin.
Stratum granulosum (granular layer) is an epidermal layer than consists of three
to fi ve layers of keratinocytes which have started to fl atten out, and their nuclei and
organelles have begun to disintegrate. Also, lipid and keratin granules have started
to form inside the keratinocytes. Eventually the granules will give rise to the brick -
and - mortar structure of the stratum corneum.
The stratum spinosum (prickly layer) is composed of several layers of keratinocytes
which are starting to exhibit histological and biochemical changes that mark
the beginning of the differentiation process. The shape of the keratinocytes has
become irregular and enzymes responsible for lipid synthesis are present.
The stratum basale is the deepest layer of the epidermis and is composed mainly
of keratinocytes with melanocytes making up approximately 10% of the cell population.
The stratum basale is one cell layer thick and is a layer of rapid cell division
where keratinocytes are rapidly dividing and giving rise to the uppermost layers of
the epidermis.
The dermis is the largest layer of the skin. It is a region of strong and fl exible
connective tissue. The dermis consists of two primary layers, the papillary layer and
the reticular layer. The papillary layer is the smallest layer of the dermis and is
composed mainly of collagen and elastin fi bers. The reticular layer is the largest
layer of the dermis and is composed of mainly dense connective tissue. The layer of
subcutaneous fat found directly beneath the dermis provides insulation and additional
mechanical support to the skin.