**6. Transdermal drug delivery**

Transdermal delivery patch usually consists of a reservoir of drug on a protective backing layer, a rate‐limiting release membrane, and an adhesive layer to attach the patch to the skin. The physicochemical of the drug suitable for transdermal delivery includes low molecular weight (<500 daltons), big molecules will have difficulty in penetrating the stratum corneum of the skin, high potency drug, water solubility (to facilitate movement of the drug out of the reservoir and to allow passage through the epidermal and dermal layers of the skin), and lipid solubility (to permit penetration of the stratum corneum of the skin). Fentanyl, a syn‐ thetic opioid agonist, is delivered by transdermal patch. For transdermal drug delivery, the penetration of the drug through the skin constitutes an additional series of diffusional and active transport steps [13].

The skin functions to maintain homeostasis of the body through temperature regulation, protection of underlying tissues, control water loss, rich sensory receptors, synthesizing of certain body chemicals, and excretion of wastes by sweating. The skin is made up of an outer epidermis and a dermis, followed by underlying tissue of subcutaneous layer (**Figure 9**). The epidermis is made up of stratified squamous epithelium and lacks blood vessels and it forms good barrier to protect the underlying tissue and blood capillaries. This becomes an impor‐ tant issue in the development of transdermal dosage forms so as to deliver the drug across the stratified layers [14].

Drug in the transdermal dosage form are generally poorly absorbed, but in the positive man‐ ner this will form a dosage form with a very controlled depot effect. It is an ideal dosage form for analgesics but the common problem is that the drug may cause focal irritation. Currently, in the market transdermal drug delivery for systemic effects is limited to very few drugs, those having low molecular weights and high lipophilicity. Transdermal drug delivery sys‐ tem may be optimized for controlled release of the drug for a steady plasma profile. This will reduced systemic side effects and may also improve efficacy of the analgesic drug. It is user‐friendly, convenient, painless, and offer prolong dosing and all this will contribute to improved compliance [15]. Examples of such dosage forms available in the market are the morphine and sufentanil patches.

Normally, transdermal system in a patch form is made up of an outer covering which forms the barrier, a drug reservoir, a control membrane to control the release of the drug, a contact adhesive applied to some or all parts of the system to make it stick to the skin surface, and a covering protective layer that is removed before the patch is applied (**Figure 10a**). The drug reservoir is sometimes replaced with a matrix of polymer where the drug is encapsulated (**Figure 10b**).

**Figure 9.** The barriers in epidermis which limit the penetration drug through the skin.

Researchers can be creative in the development of transdermal delivery system for analgesics. The followings are a few creative ideas on delivery of drug using various dermal patches with each having its own technique of engineering.

#### **6.1. Iontophoresis**

weight (<500 daltons), big molecules will have difficulty in penetrating the stratum corneum of the skin, high potency drug, water solubility (to facilitate movement of the drug out of the reservoir and to allow passage through the epidermal and dermal layers of the skin), and lipid solubility (to permit penetration of the stratum corneum of the skin). Fentanyl, a syn‐ thetic opioid agonist, is delivered by transdermal patch. For transdermal drug delivery, the penetration of the drug through the skin constitutes an additional series of diffusional and

The skin functions to maintain homeostasis of the body through temperature regulation, protection of underlying tissues, control water loss, rich sensory receptors, synthesizing of certain body chemicals, and excretion of wastes by sweating. The skin is made up of an outer epidermis and a dermis, followed by underlying tissue of subcutaneous layer (**Figure 9**). The epidermis is made up of stratified squamous epithelium and lacks blood vessels and it forms good barrier to protect the underlying tissue and blood capillaries. This becomes an impor‐ tant issue in the development of transdermal dosage forms so as to deliver the drug across

Drug in the transdermal dosage form are generally poorly absorbed, but in the positive man‐ ner this will form a dosage form with a very controlled depot effect. It is an ideal dosage form for analgesics but the common problem is that the drug may cause focal irritation. Currently, in the market transdermal drug delivery for systemic effects is limited to very few drugs, those having low molecular weights and high lipophilicity. Transdermal drug delivery sys‐ tem may be optimized for controlled release of the drug for a steady plasma profile. This will reduced systemic side effects and may also improve efficacy of the analgesic drug. It is user‐friendly, convenient, painless, and offer prolong dosing and all this will contribute to improved compliance [15]. Examples of such dosage forms available in the market are the

Normally, transdermal system in a patch form is made up of an outer covering which forms the barrier, a drug reservoir, a control membrane to control the release of the drug, a contact adhesive applied to some or all parts of the system to make it stick to the skin surface, and a covering protective layer that is removed before the patch is applied (**Figure 10a**). The drug reservoir is sometimes replaced with a matrix of polymer where the drug is encapsulated

**Figure 9.** The barriers in epidermis which limit the penetration drug through the skin.

active transport steps [13].

22 Pain Relief - From Analgesics to Alternative Therapies

the stratified layers [14].

morphine and sufentanil patches.

(**Figure 10b**).

An active state of transdermal technologies uses low voltage electrical current to drive charged drugs through the skin. This will enable charged particles of drugs to move across the stratum corneum. Each iontophoresis patch is a device consisting of a housing which contains the battery and related electronics, two polymeric reservoirs for anode and cathode, and skin adhesive. Only one of the polymeric reservoirs contains the drug. The other may contain only pharmacologically inactive ingredients. **Figure 11** depicts the iontophoresis system. The choices on whether the anode or the cathode contains the drug are dependent on the drug charge.

**Figure 10.** (a) The structure of a reservoir dermal patch. (b) Two types of structures for matrix dermal patch.

**Figure 11.** Iontophoresis patch illustration.

The technique of iontophoresis has the potential to be expanded to deliver proteins and pep‐ tides. The current can be literally switched on and off and modified, also iontophoretic delivery enables rapid onset and offset, and drug delivery is highly controllable and programmable.
