**6. Ideal drugs for dermal and transdermal delivery**

Owing to the selective nature of the skin barrier, only a small pool of drugs can be delivered systemically at therapeutically relevant rates [27]. Few drugs constitute the whole segment of the transdermal drug market. Besides great potency, the physicochemical drug characteristics often evoked as favourable for percutaneous delivery include moderate lipophilicity and low molecular weight [28]. However, a large number of pharmaceutical agents do not fulfill these criteria. This is especially true for macromolecules, such as insulin, human growth hormone or cyclosporine, which are very challenging from the drug delivery point of view. The physicochemical properties of ideal drug for transdermal delivery include:


bioequivalent if they produce comparable plasma concentration-time curves. Even though the target site for topical dermatologic drug products in some instances may not be the stratum corneum, the topical drug must still pass through the stratum corneum, except in instances of damage, to reach deeper sites of action [21]. In certain instances, the stratum corneum itself is the site of action. For example, in fungal infections of the skin, fungi reside in the stratum corneum and therefore dermatopharmacokinetic measurement of an antifungal drug in the stratum corneum represents direct measurement of drug concentration at the site of action [22]. In instances where the stratum corneum is disrupted or damaged, *in vitro* drug release may provide additional information toward the bioequivalent assessment. In this context, the drug release rate may reflect drug delivery directly to the dermal skin site without passage through the stratum corneum. For antiacne drug products, target sites are the hair follicles and sebaceous glands. In this setting, the drug diffuses through the stratum corneum, epidermis, and dermis to reach the site of action. The drug may also follow follicular pathways to reach the sites of action. The extent of follicular penetration depends on the particle size of the active ingredient if it is in the form of a suspension [21, 23-25]. Under these circumstances, the dermatopharmacokinetic approach is still expected to be applicable because studies indicate a positive correlation between the stratum corneum and follicular concentrations. Although the exact mechanism of action for some dermatological drugs is unclear, the dermatopharma‐ cokinetic approach may still be useful as a measure of bioequivalence because it has been demonstrated that the stratum corneum functions as a reservoir, and stratum corneum

For reasons thus cited, dermatopharmacokinetic principles should be generally applicable to all topical dermatological drug products including antifungal, antiviral, antiacne, antibiotic, corticosteroid, and vaginally applied drug products. The dermatopharmacokinetic approach can thus be the primary means to document bioavailability/bioequivalence. Generally, bioequivalence determinations using dermatopharmacokinetic studies are performed in healthy subjects because skin where disease is present demonstrates high variability and changes over time. Use of healthy subjects is consistent with similar use in bioequivalence

**•** a single application of the dermatological preparation damages the stratum corneum

**•** for otic preparations except when the product is intended for otic inflammation of the skin;

**•** for ophthalmic preparations because the cornea is structurally different from the stratum

Owing to the selective nature of the skin barrier, only a small pool of drugs can be delivered systemically at therapeutically relevant rates [27]. Few drugs constitute the whole segment of

concentration is a predictor of the amount of drug absorbed [26].

A dermatopharmacokinetic approach is not generally applicable when:

**6. Ideal drugs for dermal and transdermal delivery**

studies for oral drug products.

200 Application of Nanotechnology in Drug Delivery

and

corneum.

**•** Should be potent, with short half life and be non-irritating.

Overcoming low skin permeability to xenobiotics can be achieved by a variety of approaches, and is an active field of research. Their effectiveness and applicability will vary from drug to drug depending on the physicochemical nature of the compound. New drug discovery is still a complicated process and generally requires substantial time and monetary investment. Technologies for formulation change provide the benefit of improving pharmaceutical product efficacy and safety as well as patient convenience; these technologies provide a relatively simple approach to creating new pharmaceuticals compared with new drug discovery because the active compounds used in the formulation have already been approved [29-31]. Nnamani *et al* [32] developed and evaluated the antimicrobial activities of an alternative non-invasive, convenient and cost-effective transdermal drug delivery system (TDDS) containing gentami‐ cin in biodegradable polyester-based matrices. Other drugs which have been formulated for dermal and transdermal delivery are nitroglycerin, nicotine, scopolamine, clonidine, fentanyl, 17-β-estradiol, testosterone, Boswellic acid (*Boswellia serrata*) and curcumin (*Curcuma longa*).
