Permeation Enhancers:


Permeation Enhancers:

  • These substances work to improve skin permeability by altering the ability of a desired penetrant to pass through the skin. 

  • Penetration enhancers are added to a formulation to improve the diffusivity and solubility of drugs through the skin, thereby reducing the skin's barrier resistance. 

  • This allows the drug to penetrate to the viable tissues and enter the systemic circulation. 

  • The flux J of drug across the skin can be written as 

  •   J = D [dc/dx] 

  • Where,

    • J = The Flux,

    • D = diffusion coefficient, 

    • C = Concentration of the diffusing species, 

    • X = Spatial coordinate. 

  •  The methods employed for modifying the barrier properties of the SC to enhance the drug penetration (and absorption) through the skin can be categorised as chemical and physical methods of enhancement

Chemical Enhancers:

  • Chemical permeation enhancers can work by one or more of the following four principle mechanisms: 

    • Relaxation of the stratum corneum's highly ordered lipid structure. 

    • Interacting with the aqueous domain of the lipid bilayer. 

    • Enhanced drug partitioning via co-enhancer or solvent addition into the stratum corneum. 

    • Increasing penetration and creating a drug reservoir in the stratum corneum. 

  • Chemical permeation enhancers work by altering the skin structure mentioned above. 

  • Various chemical permeation enhancers interact with the polar head groups via hydrogen bonding and ionic interactions. 

  • The relaxation at the head portion is caused by the disruption of the lipid hydration spheres and it changes the head group properties. This relaxation may reduce the resistance of this lipid-enriched domain to polar molecules. 

  • Another factor is an increase in the volume of the water layer, which results in more water flow to the tissue, a process known as solvent swelling, which leads to an increased cross sectional area for polar molecule diffusion. 

  • A portion of free water, in addition to the water in structure, becomes available at the lipid interface. This can also happen as a result of simple hydration. 

  • Some of the most widely studied permeation enhancers:

  • di-methylsulfoxide (DMSO), 

  • di-methylacetamide (DMA), and 

  • diethyltoluamide (DEET), 

  • propylene glycol (PG). 

  • The penetration enhancers, such as DMSO, urea and surfactants, can also interact with the keratin filaments present in corneocytes causing disruption within the cell thereby increasing diffusion coefficient and permeability. 

Physical Enhancers:

  • Different techniques which are used are as following,

  • Electroporation.

  • Iontophoresis.

  • Ultrasound.

  • Magnetophoresis.

  • Thermophoresis.

  • Microneedle-based devices.

  • Needleless injection.

  • Electroporation:

  • Oldest method.

  • Involves the application of high voltage pulses to induce skin structure change. 

  • High voltages (≥100 V) and short treatment durations (milliseconds) are most frequently employed. 

  • The technology has been used successfully to increase the skin permeability of molecules with varying lipophilicity and size (such as proteins, peptides, oligonucleotides, and small molecules).

  • Iontophoresis:

  • This technique involves applying a low-level electric current to the skin, either directly or indirectly through the dosage form, to increase the permeation of a topically applied therapeutic agent.

  • Increase in drug permeation as a result of this methodology can be due to either one or a combination of electro-repulsion (for charged solutes), electro-osmosis (for uncharged solutes), and electro-perturbation (for both charged and uncharged) mechanisms.

  • Ultrasound:

  • Commonly called sonophoresis

  • The use of ultrasonic energy to enhance transdermal delivery of solutes, either simultaneously or through pretreatment, is referred to as ultrasound.

  • The proposed mechanism for the increase in skin permeability is the formation of gaseous cavities within the intercellular lipids in response to ultrasound, resulting in stratum corneum disruption. 

  • Magnetophoresis:

  • With this technique, a magnetic field is applied to the skin in order to improve the diffusion of a diamagnetic solute across the skin. 

  • A magnetic field applied to the skin may also cause structural changes that could increase permeability.

  • Thermophoresis:

  • The skin surface temperature is usually maintained at 32°C in humans by a range of homeostatic controls.

  • The change in skin temperature can result in changes in its structure.

  • Microneedle-based devices:

  • These micro-needles of length 50 to 110 mm used to penetrate the stratum corneum and epidermis to deliver the drug from the reservoir. 

  • Needleless injection:

    • According to reports, a painless injection technique is used to apply medications to the skin. 

    • As a result, this approach does not involve the risks, discomfort, or anxiety that come with using hypodermic needles. 

Ideal properties of penetration enhancer.

  1. It should be pharmacologically inert. 

  2. It should be nontoxic, non irritating, and non-allergenic to the skin

  3. It should produce rapid onset of action; predictable and suitable duration of action for the drug used 

  4. Following removal of the enhancer, the stratum corneum should immediately and fully recover its normal barrier property

  5. The barrier function of the skin should decrease in one direction only i.e.., they should permit therapeutic agents into the body and efflux of endogenous materials should not occur. 

  6.  It should be chemically and physically compatible with the delivery system. 

  7.  It should be non-damaging to viable cells. 

  8.  They should be Inexpensive and cosmetically acceptable. 

  9.  The Penetration enhancer used should be economical.

Commonly asked questions.

  1. What is the role of permeation enhancer in TDDS? Give ideal properties of the penetration enhancers.

  2. Discuss various methods of skin permeation techniques.

Topics u may like to read