Table 1.

The advantages and disadvantages of various transdermal delivery system

	Method	Advantages	Disadvantages	Ref.
Active Delivery	Iontophoresis	• Improving the delivery of polar molecules as well as high molecular weight compounds • Faster and easier administration • Enabling continuous or pulsatile delivery of drug	• Risk of burns if electrodes are used improperly • Difficulty stabilizing the therapeutic agent in the vehicle • Complexity of the drug release system	[25–29]
	Sonophoresis	• Allows strict control of transdermal diffusion rates • In many cases, greater patient approval • Less risk of systemic absorption • Helpful to break up blood clots • Not immensely sensitizing	• Can be prolonged to administer • Minor tingling, irritation and burning • SC must be unbroken for effective drug penetration	[30–33]
	Electroporation	• Highly effective, reproducible, directed drug transfer • Permits rapid termination of drug delivery through termination • Not immensely sensitizing	• Impossible to use on a large area • Can be disturb the cargo if high voltage is uesd • Possibility of cell damage • Relatively nonspecific	[34–36]
	Photomechanical waves	• Can improve transfer of molecules across the plasma membrane of cells in vitro without loss of viability • Not appear to cause injury to the viable skin • Do not cause pain or discomfort	• Lack of human clinical data	[37–40]
	Microneedle	• Painless administration of the active pharmaceutical ingredient • Faster healing at injection site • No fear of needle • Specific skin area can be targeted for proper drug delivery	• Lower dosing accuracy than hypodermic needles • Penetration depth of various particles depending on the skin layer • Possibility of venous collapse due to repeated injections	[41–54]
	Thermal ablation	• Avoid the pain, bleeding, and infection • Can remove SC selectively without damaging deeper tissues • Better control and reproducibility • Low cost and disposable device	• Structural changes in the skin must be evaluated • Existing concerns about the use of extreme temperatures and the logistics of such devices	[55–59]
Passive delivery	Vesicles	• Accomplish sustained drug release behavior • Control the absorption rate through a multilayered structure	• Chemically unstable • Expensive of formulations • Limitation of drug loading	[60–63]
	Polymeric nanoparticles	• Accomplish targeted and controlled release behavior • High mechanical strength and non-deformability • Can be made of various biodegradable materials • Can be loaded both hydrophilic and hydrophobic drugs • Can avoid the immune system due to small size	• Difficult to break down • Not enough toxicological assessment has been done • Some processes are difficult to scale up	[64-70]
	Nanoemulsion	• Long-term thermodynamic stability • Excellent wettability • High solubilization capacity and physical stability • Possible to formulate it in variety of formulations	• Requires large concentration of emulsifiers • Limited solubilizing capacity for high-melting substances • Variable kinetics of distribution processes and clearance	[58, 71, 72]