**7. Advantages of dermal and transdermal drug delivery**

Transdermal delivery provides convenient and pain-free self-administration for patients. It eliminates frequent dosing administration and plasma level peaks and valleys associated with oral dosing and injections to maintain constant drug concentrations, and a drug with a short half-life can be delivered easily. All this leads to enhanced patient compliance, especially when long-term treatment is required, as in chronic pain treatment and smoking cessation therapy [3,33,34].


**•** The other advantage of transdermal delivery is that multiple dosing, on-demand or variablerate delivery of drugs is possible with the latest programmable systems, adding more benefits to the conventional patch dosage forms.

**9.1. Drug solubility determination**

**9.2. Micromeritic measurements**

remain discrete.

*9.2.2. Specific surface area*

the liberation/release rate of the drug from the formulation.

method. Surface area affects spreading and occlusivity of TDDS.

**9.3. Visualization by transmission electron microscopy**

*9.2.1. Particle-size, shape and zeta potential analysis*

The determination of solubility of the drug in the transdermal/dermal matrix early in the formulation process can avoid crystallization problem, which is one of the instabilities in transdermal drug delivery systems (TDDS). This instability in the matrix which could be due to supersaturation makes the formulation metastable and upon storage results in changes in

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Light scattering is an important way of characterizing colloidal and macromolecular disper‐ sions and could be useful in assessing properties of particulate TDDS e.g. ethosomes. The particle size and size distribution are primarily measured using wet laser diffraction sizing otherwise called dynamic light scattering (DLS) [39]. Size of formulation can also be deter‐ mined using dynamic light scattering (e.g. using a Zetasizer). This is necessary to ascertain the possible effect of the size on drug release and penetration across barriers in transdermal and dermal delivery as well as to monitor stability over time. The zeta potential of a formulation is very important. It is determined using Zetsizer or by other means, and gives information on the charge of the particles and the tendency of the particles in a formulation to aggregate or to

An important parameter of bulk powders is the specific surface area expressed per unit weight. The specific surface area measurement includes the cracks, crevices, nooks, and crannies present in the particles. To include these features in the surface-area measurement, methods have been developed to probe these convoluted surfaces through adsorption by either a gas or a liquid [40-42]. The most widely used surface area measurement technique is the adsorption of a monolayer of gas, typically krypton or nitrogen as the adsorbate gas in helium as an inert diluent, using the method developed by Brunauer, Emmett, and Teller known as the BET

A combination of transmission electron microscopy (TEM) and freeze fracturing otherwise referred to as freeze fracture electron microscopy (FFEM) could be used to visualize skin structures and certain perturbations in the skin. A micrograph image is generated by trans‐ mitting a beam of electrons through a specimen appropriately treated to enhance the visuali‐ zation of skin structural details. High resolution of TEM makes it possible to visualize both structures and transition processes in the epidermis. Using different techniques, epidermal granules [43], Langerhans cells [44] and the lipids in stratum corneum and epidermis [45], amongst others, have been observed. Samples preparation in FFTEM involves freezing the sample and subsequent longitudinal fracturing approximately parallel to the original skin

