# State-of-All-the-Art and Prospective Hydrogel-Based Transdermal Drug Delivery Systems
## 2 Overview of Transdermal Drug Delivery  
Transdermal drug delivery systems (TDDSs) are drug delivery systems with controlled release mechanisms that utilize the skin as a medium for drug administration. They are formulated to perform drug delivery at a controlled and predetermined rate through systemic circulation. TDDSs focus on retaining the drug input at a sustained level for a certain period rather than on spontaneous administration [8]. Drugs permeate the skin and enter the bloodstream. The use of TDDSs dates back several years and involves applying substances or plant extracts to the skin [9]. The first systemic delivery system was designed to treat motion sickness using a 3-day scopolamine patch [9]. Additional instances involve the application of transdermal patches for administering medications like nicotine, fentanyl, nitroglycerin, and clonidine to address diverse medical conditions [10]. Like other drug delivery systems, TDDSs also have their advantages and disadvantages of being chosen as a method of drug delivery. The main advantages and disadvantages are listed in Table 1.  
Generally, transdermal drug delivery is carried out via a patch that can be directly attached to the desired area. It comprises a backing layer, drug, membrane, adhesive, and liner, as portrayed in Figure 1. The topmost layer of the patch, referred to as the backing layer, protects the underlying layers from the external environment. Typically composed of pliable and waterproof materials like polyethylene or polypropylene, this layer features an adhesive coating that secures the patch to the skin, ensuring its proper placement [10]. It is usually made of a strong and mild hypoallergenic adhesive. The drug layer holds substances intended for transdermal delivery. Its formulation is designed to release drugs consistently over a specified period. A rate control membrane regulates the release pace of drugs from the patch. Typically made of semi-permeable materials, these membranes permit controlled drug passage. The liner serves as a protective layer for both the patch and adhesive. Before application to the skin surface, it is essential to remove the patch [16].  
\begin{table}
\begin{tabular}{l l} \hline \hline
**Advantages** & **Disadvantages** \\ \hline \hline \begin{tabular}{l} Mitigate problems from the gastrointestinal \\ tract (GIT) and hepatic metabolism [11]. \\ \end{tabular} & Poor permeability across the skin [12] \\ \hline \hline \begin{tabular}{l} Noninvasive drug administration and less pain \\ involved [13] \\ \end{tabular} & \begin{tabular}{l} Few classes of drugs exhibit skin \\ penetration [14] \\ \end{tabular} \\ \hline \hline \begin{tabular}{l} Provide drug release for an extended period [9] \\ \end{tabular} & Slow drug release \\ \hline \hline \
\begin{tabular}{l} Maintain a steady plasma level of the drug [15] \\ \end{tabular} & May cause local irritation \\ \hline
\begin{tabular}{l} Increased patient compliance \\ \end{tabular} & Variation in barriersd [12] \\ \hline \hline \end{tabular}
\end{table}
Table 1: Advantages and Disadvantages of TDDS.  
TDDSs can be broadly categorized into matrix, drug-in-adhesive, reservoir, and micro-reservoir systems according to their design [10]. However, commercially available transdermal systems are either of the reservoir or matrix types [16; 17]. Figure 2 represents different types of transdermal systems. Reservoir-type patches store the drug in a solution or gel, with its distribution regulated by a rate-control membrane placed between the drug reservoir and the skin [8]. Conversely, matrix-type patches feature a straightforward design involving the incorporation of drugs into adhesive [8].  
Figure 1: Key Components of Transdermal Drug Delivery Systems (TDDS).  
Figure 2: Different types of transdermal patches: (**a**) the drug-in adhesive system; (**b**) the reservoir system; (**c**) the matrix system; (**d**) the micro-reservoir system [12].