Factors influencing dermal penetration of drugs
The skin’s ability to absorb substances depends on several factors:
Concentration
Molecular Weight of the molecule
Duration of contract
Solubility of medication
The physical condition of the skin
Part of the body is exposed including the amount of hair on the skin
Penetration Enhancers
Making it more difficult for drugs to penetrate the skin, Besides reversibly modifying the structure of the stratum corneum by reversibly disarranging the lamellar packing, penetration enhancers increase the thermal activity of a drug and hence its permeation through the skin.
An alternative class of penetration enhancers increases the amount of solubilized drug molecules at the skin’s surface, which results in the enhanced permeability of lipophilic drug molecules.
They are employed to transfer the delivery of drugs that are ionizable (Example: timolol maleate) and
impermeable (Example: heparin); to maintain drug levels in the blood, to provide a higher dose of less potentially active drugs (Example: Oxymorphane), to deliver high molecular weight hormones and
peptides and to lessen the lag time of the transdermal drug delivery system
Approaches for permeation enhancement
a) Chemical approach
b) Biochemical approach
c) Physical approach
The main focus is to prepare absorption enhancement systems that produce zero to no skin irritation. Their clinical application is limited by the fact that mostly this increased enhancement leads to toxicity. Permeation enhancers can be used as a tool to achieve an effective dosage of the drug to enter therapeutically within the skin.
To obtain substances that fully meet the optimal requirements, one approach is to synthesize
penetration enhancers by understanding the interaction of enhancers and developing structural
activity relationships. This can be done using modern discovery and modelling techniques which
aims to produce structures with minimal toxicity and optimal characteristics.
