What Are The Influencing Factors of Drug Percutaneous Absorption
In the clinical transdermal drug delivery process, there are many factors that affect the transdermal absorption of the drug, mainly including: skin hydration, skin temperature, skin conditions, and skin locations.
Skin Hydration
The phenomenon that the water content of the skin exceeds the normal state is called skin hydration. After the skin is saturated with water, the tissue softens, swells, wrinkles disappear, and the permeability increases significantly. Skin hydration promotes transdermal absorption of drugs. The encapsulation method or the application of ointment on the skin reduces the evaporation of skin moisture, and the covering effect increases the endogenous hydration of the stratum corneum and increases skin penetration. The hydration of the stratum corneum can increase the moisture content of the skin from the normal value of 10%- 25% to 50%-70%, and the thickness also increases to 48nm. The increase in the amount of intercellular water expands the diffusion pathway of water molecules, and the intercellular space becomes larger, which promotes drug penetration. Among them, skin hydration mainly increases the penetration of non-polar fat-soluble molecules, and has little effect on the penetration of polar molecules.
Skin Temperature
The skin temperature rises by 10 degrees, and the penetration is increased by 1.4 to 3.0 times. The effect of temperature on the transdermal penetration of drugs is manifested in three aspects: 1 The process of drug penetration through the skin requires energy, and the increase in temperature increases the penetration rate of the drug; 2 The increase in temperature causes dermal vasodilation, and the increase in blood flow facilitates absorption; 3 Elevated temperature causes sweating, hydrates the stratum corneum, and increases permeability. When indomethacin, ibuprofen and other non-steroidal anti-inflammatory drugs penetrate through the skin of nude mice, when the temperature rises from 27 degrees to 37 degrees, the permeability coefficient increases by 10 times. The main reason is that the activity coefficient of the drug in the skin decreases and the solubility increases; secondly, within the range of 25 to 45 degrees (the phase transition of the stratum corneum occurs at 42 to 70 degrees), the degree of freedom and speed of the hydrocarbon chain movement increases. The fluidity of lipid channels is improved, and the permeability coefficient of fat-soluble drugs can be increased by 100 to 1000 times.
Skin Condition
Transdermal penetration studies usually use normal, healthy skin as a model, and actual skin conditions change with age. The fetal stratum corneum begins during pregnancy and is formed at birth. Babies may not have a well-developed stratum corneum, and their skin is more permeable. The structure and function of the adult skin are constantly improving, and the permeability is constantly changing. It is generally believed that children’s skin is more permeable than adults. Skin damage is often caused during the preparation and treatment of isolated skin. Abrasions are the most common, often causing congestion and local damage. Careless peeling is another possible cause of skin damage. The penetration amount of hydrocortisone to peeled skin can reach 90% of the administered dose, while for intact skin it is only 2% or less. Chemical reagents can damage the skin；treatment of hairless mice with ultraviolet rays, tretinoin or 10% acetone acetate solution can cause damage and increase penetration. Many chemical agents can significantly change the nature of the skin barrier and destroy the structure of the stratum corneum. The mixture of non-polar solvents such as chloroform and polar solvents such as methanol can remove lipids in the stratum corneum, forming artificial channels in the film, making it easier for molecules to permeate. Hexane, acetone, and ethanol can all increase the permeability of water in the skin. Dimethyl sulfoxide (DMSO), dimethyl formamide (DMF), dimethyl acetamide (DMA), etc. are commonly used as penetration enhancers. Skin diseases are the most common cause of changes in skin conditions. Skin inflammation is first manifested as swelling, redness, and exudation of secretions, and scaly and crusting after the formation of blisters. In short, skin diseases are always accompanied by stratum corneum defects and increased transdermal absorption.
Skin Area
The skin permeability of different parts of the body varies greatly. The thickness of the stratum corneum of the flexor muscles of the abdomen, back, thigh, and forearm were 8.9um, 9.4um, 12.9um and 12.9um, respectively. The stratum corneum has an average thickness of 19 cells, each cell thickness is 0.55μm, and the average total thickness is approximately 12.4μm. Choosing a suitable skin site is the key to the study of transdermal absorption preparations.