Rick Williams – Cosmeputics International, Australia FORMULATING
Development considerations with maximum effect
This two-part article will outline the basic problems in getting an active ingredient to enter the skin via topical absorption through the epidermis. Iwill detail the physical problems preventing this associated with the skin’s natural barrier system, the rate of absorption and how we can modify this process to enhance absorption for skin rejuvenation or reduce absorption in the case of sunscreens. The product parameters discussed will be the emulsifier, the emollients, the formulation type, the active ingredient itself and the additives that can affect skin penetration. Particular examples used will be to explain the effects of skin lighteners.
The epidermis The skin has a defined structure although the various layers may vary in thickness from area to area. The epidermis is the superficial protective layer at the surface. It varies in thickness from 0.007 mm to 0.12 mm and is composed of stratified squamous epithelium. The process of keratinisation occurs in the epidermis where the keratinocytes (cells that produce keratin), are found. As new cells are formed, they move further away from the sources of nutrients (i.e. blood vessels) and eventually degenerate and die. The remains are almost pure keratin which, because of the overlapping matrix layers and the fact that keratin is a hard, waterproofing protein, act as the outer physical barrier. The stratum corneum is the outermost
layer, and consists of approximately 25 layers of dead, flat cells composed of keratin, with protein deposits. These cells act as the primary physical protective layer and compose the layer that any drug, applied to the surface, must penetrate to have any chance of being absorbed into the body. The outermost cells are continuously lost but are also continually replaced with cells from lower layers (desquamation). It can take from 40 to 55 days from cells to move from the stratum basale to the surface (ie. across the epidermis) although this rate will change with age (becoming slower) or illness (eg.
The third layer is the stratum
granulosum. This layer (three or four rows of flattened cells) is where the cells begin to die and because of this have a granular appearance, hence its name. Site of formation of keratin complex and lipid synthesis – these lipids form the intracellular cement. The fourth layer is the stratum spinosum
in eczema, psoriasis or skin cancers it becomes quicker). The two billion cells which make up the skin are in constant renewal, three hundred million of them being replaced on a daily basis. This desquamation acts to mechanically remove pathogens and other contaminants that are trapped in the outer layer of the epidermis, but obviously removes beneficial drugs applied to the skins surface as well. The intercellular channels between the
layers in the stratum corneum are composed of a lamellar structure of lipid layers (nearest the cells) and water layers between. The water layer is lined with surface active agents that have a polar nature. It is this polar nature that restricts polar chemicals (eg. water soluble vitamins, amino acids and almost all water soluble drugs) from penetrating. The second layer of the epidermis is
the stratum lucidium. This layer is more prominent in pressure sensitive areas such as the palms of the hand and soles of the feet. This acts as an extra barrier to physical attack from large sharp objects. The layer consists of rows of clear, flat, dead cells. They contain eleidin, the precursor to keratin production.
which contains several stratified layers of living cells, although no new cells are produced in this layer. This is the site of active protein synthesis generating tonofibrils of keratin that migrate to the granular layer. The cells are not flat but have an irregular shape with sharp edges, giving them a spiny appearance. This layer contains Langerhans cells (non-pigmented granular dendrocytes that are associated with the internal protection of the skin) and activation of these cells is believed to improve the skin’s protective ability against chemical attack. The inner (fifth) layer of the epidermis
is the stratum basale. This is a single layer of cells consisting of keratincytes, melanocytes and tactile cells. Basal keratinocytes divide and migrate to other layers. Melanocytes contain the pigment forming protein, melanin, which is activated by UV light and gives the skin its ethnic coloured characteristic, a tanned appearance in lighter skin types or such non-uniform features such as freckles and sunspots. To affect skin colour, this is the layer we must find a pathway to. Sometimes scientists refer to the
stratum spinosum and stratum basale together, referred to as the stratum germinativum or the germative layer as here the skin cells we see are produced.
The dermis The dermis is the connective layer of the skin (connecting the subcutaneous layer and the epidermis) comprising collagen and elastin. Because of this the dermis gives the skin its strength, extensibility, elasticity and ‘tone’. It is also thick in the palms of the hand and soles of the feet while very thin in areas that require extra sensitivity (eyelids, mucous membranes
March 2012 PERSONAL CARE 23
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