Page 43 - Pharmaceutics-II (02-06-01 203)

• Temperature: high temperature causes an increase in the kinetic energy of the drug
molecules and structure alteration in the stratum corneum increases drug penetration

• Skin hydration: hydration of the skin through soaking, moisturizing, or humidity causes
the corneocytes in the SC to swell and increases drug penetration

• Skin condition: the rate of transdermal absorption would change according to skin
condition

Inflamed skin loses stratum corneum and has altered keratinization, resulting in increased
permeability
If the organ thickened with corns, calluses, and warts, the drug permeation should decrease
In diseases characterized by a defective stratum corneum, percutaneous absorption usually
increases.
Thus, a psoriatic plaque may take up twice as much 8-methoxy psoralen as does uninvolved skin

• Skin metabolism: The skin metabolizes steroid hormones, chemical carcinogens, and some
drugs

Enzymatic activity is a rate-limiting factor and is highest in the viable epidermis of the skin which
reduces with age

• Race: racial differences in skin function alter drug penetration
B. Physiochemical factors (5 main factors)
Solubility and pH of the drug:
Solubility of the drug in both oil and water is very important for effective percutaneous
absorption
Solute with adequate solubility in mineral oil and water (>1mg/ml) can permeate through skin
Moderate pH is favourable because if solution with high or low pH will destroy the skin
Partition coefficient:
Molecules with a log p value of 1-3 have both aqueous and lipophilic properties, sufficient
enough to obtain proper transdermal permeation because they are able to cross the lipophilic
(SC) and hydrophilic layers (epidermis) of the skin
Drug concentration:
One requirement for maximal flux is that the donor solution should be saturated
A formulator can optimize the solubility of a drug such as a corticosteroid by controlling the
solvent composition of the vehicle.
The higher the concentration of the drug in the vehicle the faster the absorption

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