Skin Penetration Routes of Topical Anesthesia.

Introduction:

Transdermal drug delivery systems (TDDS) are discrete, self-contained dosage forms that release medication(s) to the systemic circulation through the skin. Human skin is a very effective barrier because of the stratum corneum. Transdermal drug delivery uses chemical enhancers to cross the skin barrier, bypassing the gastrointestinal tract and preventing the first-pass effect.

The skin is the preferred route for both local anesthetic and the treatment of dermatological conditions. Topical drug delivery may minimize the necessity for systemic drug administration, lower the overall dosage needed, and lessen the risk of unwanted reactions. In addition, topical administration helps treat skin inflammations, photoaging, microbial and fungal infections, and skin cancer.

The primary barrier to transdermal transfer was a layer of cells connecting the epidermis to the stratum corneum, the skin's thin, outermost layer. The use of penetration enhancers promotes drug transport through the epidermal barrier. One method to improve penetration is through the enhancers' interaction with the lipids' polar head groups. In addition, surfactants and keratin interactions can dissolve stratum corneum lipids, acting as penetration enhancers.

What Is the Target Site for Transdermal Drug Delivery System?

The stratum corneum, which acts as a superficial barrier, determines the drug's absorption rate into the deeper layers of the skin. As the skin is hydrophilic, this nature increases from the surface (stratum corneum) to the deeper layers of the skin (stratum basale).

What Are the Skin Barriers against Percutaneous Absorption?

Corneocytes, the stratum corneum's building blocks, are held together by corneodesmosomes to aid in the structural stability and maintain the cohesiveness of the stratum corneum made up of ceramides, cholesterol, cholesterol sulfate, and fatty acids that are arranged into multi-lamellar bilayers. On a dry weight basis, the stratum corneum's diverse structure consists of around 75 to 80 % protein, 5 to 15 % lipid, and 10 to 20 % unidentified proteins.

The drug substances permeate the stratum corneum through the transepidermal route and pores.

What Are the Factors Affecting Skin Penetration?

• The thickness of the horny layer.

• Skin condition.

What Are the Factors Associated With Medicament?

• Solubility.

• Dissociation constant.

• Particle size.

What Are the Factors Associated with the Vehicle Present in the Drug?

• Contact with skin.

• Penetration into the epidermis.

• Alteration of skin permeability.

What Are the Routes of Drug Permeation through the Skin?

• Intercellular route.

• Transcellular route.

• Follicular route.

What Are the Methods of Modifying Barrier Properties of Stratum Corneum?

To improve the drug's penetration and absorption into the deeper layers of the skin, they are classified into the following categories.

• Chemical enhancement.

• Physical enhancement.

• Biochemicalenhancement.

• Supersaturation enhancement.

• Bioconvertable prodrug.

What Are Penetration Enhancers?

Chemical penetration enhancers are one method of improving drug penetration through the stratum corneum barrier (sorption promoters or permeation enhancers and accelerants).

What Is the Mechanism of Action of Permeation Enhancers?

Chemical permeation enhancers function through three main processes listed below:

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

• Interacting with the aqueous portion of the lipid bilayer.

• Increased drug partition caused by solvent or enhancer addition to the stratum corneum.

By causing the earlier changes to the skin's structure, they exert their effects in the following manner:

• First, increase the drug's skin absorption rate.

• Cause the stratum corneum's lipids to fluidize, reducing barrier function (a reversible effect).

• Finally, the thermodynamic activity of the drug in the vehicle and the skin should be improved and increased.

• Increase and optimize the thermodynamic activity of the drug in the vehicle and the skin; cause the skin to become a drug reservoir.

• Alter the drug's partition coefficient, boosting the drug's release from the formulation into the skin's top layers.

• Binding to the keratin filament causes the corneocyte's internal and external order to be upset.

What Are the Ideal Properties of the Penetration Enhancers?

• It should be pharmacologically inactive.

• It should be non-poisonous and not cause any irritation to the skin or cause allergies.

• It should have a quick start of the effect, predictable duration, and appropriate duration for the medicine being utilized.

• The stratum corneum should promptly and thoroughly regain its usual barrier property once the enhancer has been removed.

• The skin's barrier function should only deteriorate in one direction, allowing therapeutic medicines to enter the body while preventing the outflow of endogenous elements.

• The delivery mechanism should be physically and chemically compatible with it.

• It should not harm healthy cells in any way.

• The use of a penetration enhancer should be cost-effective.

What Is a Surfactant?

A substance is positively absorbed in liquid, vapor, and other interfaces. They are both amphiphilic compounds containing hydrophilic groups (heads) and hydrophobic groups (tails). In skin applications, they are used as emulsifiers.

What Is the Classification of Surfactants?

Surfactants may be divided into four major types based on the presence of formally charged groups:

• Anionic (Example: Sodium lauryl sulfate).

• Cationic (Example: Cetyl trimethyl ammonium bromide).

• Non-ionic (Example: Polyoxyethylene sorbitan monopalmitate).

• Amphoteric (Zwitterions) (Example: N-dodecyl-N, N-dimethyl betaine).

What Is the Mechanism of Action of Surfactants as Penetration Enhancers?

1. Anionic Surfactants: Strong interactions between anionic surfactants, keratin, and lipids. Changing the skin's permeability by affecting the stratum corneum's helical filaments leads to the uncoiling and expansion of keratin filaments to generate keratin. They then force the membrane to expand, increasing permeability. By increasing the fluidity of epidermal lipids, sodium lauryl sulfate (SLS) can enhance penetration into the skin.

2. Cationic Surfactants: The cationic surfactants come in contact with the cornified cells' keratin fibrils, disrupting the cell-lipid matrix. In addition, the cationic surfactants interact with anionic components, altering the stratum corneum's electronic properties and promoting the absorption of the anionic medication into the skin.

3. Non-Ionic Surfactants: Non-ionic surfactants improve absorption by inducing fluidization of the stratum corneum lipids. There are two mechanisms by which the non-ionic surfactants increase the transport rat.Firstly, the surfactants may enter the intercellular spaces of the SC, improve fluidity, and eventually solubilize and release lipid components. Secondly, a disturbance within the corneocyte may occur due to the surfactant's entry into the intercellular matrix and subsequent interactions and binding with keratin filaments.

4. ZwitterIon: Zwitterions have both anions and cations linked to the same molecules.

5. Biosurfactants: Biosurfactants improve the emulsification of hydrocarbons, solubilize hydrocarbon contaminants, and improve their availability for microbial degradation.

What Are the Factors Governing the Activity of Surfactant as Penetration Enhancer?

• Critical micelle concentration.

• Chain length of carbon atoms.

• Transdermal gradient.

• The hydrophilicity of the surfactant head (Laughlin’s hypothesis).

What Are the Physical Enhanced Methods of Transdermal Drug Delivery?

1. Iontophoresis: In the stratum corneum, the application of electrical current creates micropores.

2. Sonophoresis: Phonophoresis or ultrasound refers to the drug's passage through the skin with or after using ultrasound. Cavitation and disturbance of the stratum corneum caused by ultrasound.

3. Microneedles: Formation of micropores in stratum corneum.

4. Velocity-Based Enhancers: Usage of high voltage to pierce the skin.

5. Thermal Ablation: After laser therapy, microchannels start forming in the stratum corneum.

Conclusion:

Skin penetration techniques have been used widely for treating skin cancers, inflammatory skin diseases, alopecia, and aphthous ulcers and dermatological uses. Transdermal drug delivery systems would provide good pain relief post-surgery. Further research is needed to improve the skin penetration of the drug without any skin irritation.