The permeation of the drug involves the following steps:

1. Sorption by stratum corneum
2. Penetration of drug through viable epidermis
3. Uptake of the drug by the capillary network in the dermal papillary layer

The rate of permeation across the skin (dQ/dt) is given by the expression

 

dQ/dt = Ps(Cd – Cr)

 

where

Cd = Concentration of the skin penetrant in the donor compartment (on the surface of the stratum corneum)

Cr = Concentration of the skin penetrants in the receptor compartment (body)

Ps = Overall permeability coefficient of the skin tissues to the penetrants

The permeability coefficient is given by the relationship

 

Ps = KsDss/Hs

 

where

Ks = Partition coefficient for the interfacial partitioning of the penetrant molecule from a solution medium on to the stratum corneum

Dss = Apparent diffusivity for the steady state diffusion of the penetrant molecule through a thickness of the skin tissues

Hs = Overall thickness of skin tissues

As Ps, Ks, Dss, and Hs are constant under given conditions, the permeability coefficient (Ps) for skin penetrants can be considered to be a constant.

With the introduction of various penetration enhancers, drug delivery through the transdermal route has been enhanced severalfold by altering the structure of the skin (by modifying the diffusion coefficient) or by increasing the solubility of the drug in the skin. Table 7.1 provides a list of permeation enhancers and the drugs using those enhancers.

 

Table 7.1 Permeation Enhancers Used with Drugs

SI. No.	Permeation Enhancer	Drug Used
1.	Menthol, carvacrol, linalool	Propranolol hydrochloride
2.	Limonene	Indomethacin, ketoprofen
3.	Geraniol, nerolidol	Diclofenac sodium
4.	Oleic acid	Piroxicam
5.	Lecithin	Hydrocortisone acetate, heparin
6.	Propylene-glycol-dipelargonate	Heparin
7.	Cyclodextrins	Hydrocortisone

The mechanism of permeation enhancers involves the following steps:

1. Reversibly disordering the lamellar packing of stratum corneum
2. Increasing the thermodynamic activity of the drug
3. Increasing the amount of drug in solubilized form at the skin surface

Along with penetration enhancers, inclusion of cosolvents that deliver a drug in solubilized form has resulted in higher drug permeability. Table 7.2 provides a list of drugs that use a combination of permeation enhancers and cosolvents.

 

Table 7.2 Drugs Using Combination of Permeation Enhancers and Cosolvents